{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:29:20Z","timestamp":1791322160232,"version":"4.3.1"},"reference-count":361,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Fracture nonunion remains an unresolved complication after extremity fracture, with notable costs to patient quality of life and health systems. Nonunion is defined by the inability of fracture ends to unite without evidence of progressive healing over time. Approximately 2 to 10% of all fractures go onto nonunion, with increased rates observed in specific fracture locations and patient populations. Despite advances in fixation techniques and bone grafting, current treatments remain limited and frequently fail to restore durable bone healing. In this review, the current state of emerging biologic and bioengineering therapies for nonunion will be summarized, with a focus on how these advances may shift treatment from palliative reconstruction toward durable healing. Biological therapies such as growth factors, stem cells, and gene-modified constructs show promise but face challenges of short half-life, inconsistent efficacy, and safety concerns. Emerging approaches, including controlled-release scaffolds, immunomodulatory materials, stem cell-derived exosomes, and gene therapy platforms, offer opportunities to more precisely restore the osteogenic, angiogenic, and immunologic environment required for union.<\/jats:p>","DOI":"10.3390\/pharmaceutics17111457","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T10:56:27Z","timestamp":1762858587000},"page":"1457","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Modern Approaches and Emerging Biological Therapies to Treat Fracture Nonunion"],"prefix":"10.3390","volume":"17","author":[{"given":"Julian","family":"Wier","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Shelby","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Bergren","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph T.","family":"Patterson","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1374-8929","authenticated-orcid":false,"given":"Jay R.","family":"Lieberman","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"},{"name":"Alfred E. Mann Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4884","DOI":"10.1097\/JS9.0000000000002449","article-title":"Global Burden, Trends and Forecast Analysis of Extremity Fractures Based on GBD 2021","volume":"111","author":"Wang","year":"2025","journal-title":"Int. J. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00198-023-06907-3","article-title":"Global Burden of Hip Fracture: The Global Burden of Disease Study","volume":"35","author":"Feng","year":"2024","journal-title":"Osteoporos. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1080\/17453674.2017.1321351","article-title":"The Risk of Non-Union per Fracture: Current Myths and Revised Figures from a Population of over 4 Million Adults","volume":"88","author":"Mills","year":"2017","journal-title":"Acta Orthop."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e162775","DOI":"10.1001\/jamasurg.2016.2775","article-title":"Epidemiology of Fracture Nonunion in 18 Human Bones","volume":"151","author":"Zura","year":"2016","journal-title":"JAMA Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.injury.2011.03.046","article-title":"Treatment of Long Bone Non-Unions with Polytherapy: Indications and Clinical Results","volume":"42","author":"Calori","year":"2011","journal-title":"Injury"},{"key":"ref_6","first-page":"218","article-title":"Current Strategies in the Prevention and Management of Infection in Open Fractures","volume":"7","author":"Roberts","year":"2025","journal-title":"J. Orthop. Sports Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/j.jhsa.2008.04.026","article-title":"Treatment of Scaphoid Fractures and Nonunions","volume":"33","author":"Kawamura","year":"2008","journal-title":"J. Hand Surg. Am."},{"key":"ref_8","first-page":"43","article-title":"Nonunion of the Fractured Clavicle: Evaluation, Etiology, and Treatment","volume":"9","author":"Jones","year":"2000","journal-title":"J. South. Orthop. Assoc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.2106\/JBJS.23.01160","article-title":"Association Between Periprosthetic Joint Infection and Mortality Following Primary Total Hip Arthroplasty","volume":"106","author":"Mundi","year":"2024","journal-title":"J. Bone Jt. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1186\/s13018-020-01904-2","article-title":"Prevalence and Influencing Factors of Nonunion in Patients with Tibial Fracture: Systematic Review and Meta-Analysis","volume":"15","author":"Tian","year":"2020","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1530\/EOR-21-0137","article-title":"Risk Factors for Nonunion Following Surgically Managed, Traumatic, Diaphyseal Fractures: A Systematic Review and Meta-Analysis","volume":"7","author":"Jensen","year":"2022","journal-title":"EFORT Open. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1097\/00003086-199405000-00029","article-title":"Delayed Unions and Nonunions of Open Tibial Fractures: Correlation with Arteriography Results","volume":"302","author":"Dickson","year":"1994","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"112303","DOI":"10.1016\/j.injury.2025.112303","article-title":"Open Fractures of the Lower Leg: Outcome and Risk-Factor Analysis for Fracture-Related Infection and Nonunion in a Single Center Analysis of 187 Fractures","volume":"56","author":"Schnetz","year":"2025","journal-title":"Injury"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1097\/BOT.0000000000000488","article-title":"Factors Associated with Development of Nonunion or Delayed Healing After an Open Long Bone Fracture: A Prospective Cohort Study of 736 Subjects","volume":"30","author":"Westgeest","year":"2016","journal-title":"J. Orthop. Trauma."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e326","DOI":"10.1097\/BOT.0000000000002602","article-title":"Where Are We in 2022? A Summary of 11,000 Open Tibia Fractures Over 4 Decades","volume":"37","author":"Castillo","year":"2023","journal-title":"J. Orthop. Trauma"},{"key":"ref_16","unstructured":"Thomas, J.D., and Kehoe, J.L. (2025). Bone Nonunion. StatPearls, StatPearls Publishing."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"129085","DOI":"10.52965\/001c.129085","article-title":"State of the Nonunion: A Review of the Latest Literature","volume":"17","author":"Ghanem","year":"2025","journal-title":"Orthop. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1302\/2046-3758.54.2000628","article-title":"The Radiographic Union Scale in Tibial (RUST) Fractures","volume":"5","author":"Leow","year":"2016","journal-title":"Bone Jt. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mouliou, D.S. (2023). C-Reactive Protein: Pathophysiology, Diagnosis, False Test Results and a Novel Diagnostic Algorithm for Clinicians. Diseases, 11.","DOI":"10.3390\/diseases11040132"},{"key":"ref_20","first-page":"169","article-title":"Universal Long Bone Nonunion Classification","volume":"18","author":"Solomin","year":"2023","journal-title":"Strateg. Trauma. Limb Reconstr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.bone.2014.07.033","article-title":"Bone Fracture Healing: Cell Therapy in Delayed Unions and Nonunions","volume":"70","author":"Rosset","year":"2015","journal-title":"Bone"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.injury.2020.11.029","article-title":"Fracture Nonunion in Long Bones: A Literature Review of Risk Factors and Surgical Management","volume":"52","author":"Nicholson","year":"2021","journal-title":"Injury"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"110929","DOI":"10.1016\/j.injury.2023.110929","article-title":"The Effect of Post-Traumatic Long Bone Non-Unions on Health-Related Quality of Life","volume":"54","author":"Vincken","year":"2023","journal-title":"Injury"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.2106\/JBJS.N.01090","article-title":"Time Trade-Off as a Measure of Health-Related Quality of Life: Long Bone Nonunions Have a Devastating Impact","volume":"97","author":"Schottel","year":"2015","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s00264-014-2629-y","article-title":"Long-Term Functional Outcome and Quality of Life after Successful Surgical Treatment of Tibial Nonunions","volume":"39","author":"Wichlas","year":"2015","journal-title":"Int. Orthop."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1302\/2046-3758.144.BJR-2024-0150.R2","article-title":"Direct and Indirect Costs of Long Bone Fracture Nonunions of the Lower Limb","volume":"14","author":"Maisenbacher","year":"2025","journal-title":"Bone Jt. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.injury.2014.04.002","article-title":"Delayed Union and Nonunions: Epidemiology, Clinical Issues, and Financial Aspects","volume":"45","author":"Hak","year":"2014","journal-title":"Injury"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1007\/s00264-025-06567-4","article-title":"Anxiety in Trauma Patients with Nonunion Diaphyseal Bone Fractures","volume":"49","author":"Noferesti","year":"2025","journal-title":"Int. Orthop. SICOT"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Johnson, L., Igoe, E., Kleftouris, G., Papachristos, I.V., Papakostidis, C., and Giannoudis, P.V. (2019). Physical Health and Psychological Outcomes in Adult Patients with Long-Bone Fracture Non-Unions: Evidence Today. J. Clin. Med., 8.","DOI":"10.3390\/jcm8111998"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.2106\/JBJS.L.00803","article-title":"The Devastating Effects of Tibial Nonunion on Health-Related Quality of Life","volume":"95","author":"Brinker","year":"2013","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.injury.2009.02.007","article-title":"A Health Economic Analysis of the Use of rhBMP-2 in Gustilo\u2013Anderson Grade III Open Tibial Fractures for the UK, Germany, and France","volume":"40","author":"Alt","year":"2009","journal-title":"Injury"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e337","DOI":"10.1097\/OI9.0000000000000337","article-title":"The Economic Impact of Infection and\/or Nonunion on Long-Bone Shaft Fractures: A Systematic Review","volume":"7","author":"Flores","year":"2024","journal-title":"OTA Int."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Antonova, E., Le, T.K., Burge, R., and Mershon, J. (2013). Tibia Shaft Fractures: Costly Burden of Nonunions. BMC Musculoskelet. Disord., 14.","DOI":"10.1186\/1471-2474-14-42"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.1016\/j.injury.2021.08.023","article-title":"Fracture-Related Infection in Long Bone Fractures: A Comprehensive Analysis of the Economic Impact and Influence on Quality of Life","volume":"52","author":"Iliaens","year":"2021","journal-title":"Injury"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s00402-001-0358-3","article-title":"An Economic Evaluation of Early versus Delayed Operative Treatment in Patients with Closed Tibial Shaft Fractures","volume":"122","author":"Sprague","year":"2002","journal-title":"Arch. Orthop. Trauma. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1080\/17453670510041808","article-title":"An Economic Analysis of Management Strategies for Closed and Open Grade I Tibial Shaft Fractures","volume":"76","author":"Busse","year":"2005","journal-title":"Acta Orthop."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1302\/2046-3758.93.BJR-2019-0089.R1","article-title":"Cigarette Smoke Inhalation Impairs Angiogenesis in Early Bone Healing Processes and Delays Fracture Union","volume":"9","author":"Chang","year":"2020","journal-title":"Bone Jt. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1002\/jor.23235","article-title":"Alcohol-Related Deficient Fracture Healing Is Associated With Activation of FoxO Transcription Factors in Mice","volume":"34","author":"Roper","year":"2016","journal-title":"J. Orthop. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrrheum.2012.1","article-title":"Fracture Healing under Healthy and Inflammatory Conditions","volume":"8","author":"Claes","year":"2012","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s40139-020-00209-7","article-title":"Impact of Alcohol on Bone Health, Homeostasis and Fracture Repair","volume":"8","author":"Eby","year":"2020","journal-title":"Curr. Pathobiol. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Huston, P. (2023). Why Osteoarthritis of the Knee Is Called \u201ca Wound That Does Not Heal\u201d and Why Tai Chi Is an Effective Treatment. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1208326"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s11914-015-0286-8","article-title":"Diabetes and Its Effect on Bone and Fracture Healing","volume":"13","author":"Jiao","year":"2015","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Tarantino, U., Cariati, I., Greggi, C., Gasbarra, E., Belluati, A., Ciolli, L., Maccauro, G., Momoli, A., Ripanti, S., and Falez, F. (2021). Skeletal System Biology and Smoke Damage: From Basic Science to Medical Clinic. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126629"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"193","DOI":"10.2174\/1874325001105010193","article-title":"The Aseptic Femoral and Tibial Shaft Non-Union in Healthy Patients\u2013An Analysis of the Health-Related Quality of Life and the Socioeconomic Outcome","volume":"5","author":"Zeckey","year":"2011","journal-title":"Open Orthop. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1074\/jbc.271.3.1544","article-title":"Biochemical Characterization of Human Collagenase-3","volume":"271","author":"Smith","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.bbrc.2006.12.234","article-title":"Impaired Bone Fracture Healing in Matrix Metalloproteinase-13 Deficient Mice","volume":"354","author":"Kosaki","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.ajhg.2009.01.025","article-title":"Genome-Wide Association and Follow-Up Replication Studies Identified ADAMTS18 and TGFBR3 as Bone Mass Candidate Genes in Different Ethnic Groups","volume":"84","author":"Xiong","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41413-022-00219-8","article-title":"Bone Remodeling: An Operational Process Ensuring Survival and Bone Mechanical Competence","volume":"10","author":"Bolamperti","year":"2022","journal-title":"Bone Res."},{"key":"ref_49","unstructured":"Sheen, J.R., Mabrouk, A., and Garla, V.V. (2025). Fracture Healing Overview. StatPearls, StatPearls Publishing."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.clinbiomech.2006.01.003","article-title":"Mechanical Conditions in the Initial Phase of Bone Healing","volume":"21","author":"Epari","year":"2006","journal-title":"Clin. Biomech."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6663","DOI":"10.1016\/j.actbio.2013.01.014","article-title":"Micromotion-Induced Strain Fields Influence Early Stages of Repair at Bone-Implant Interfaces","volume":"9","author":"Wazen","year":"2013","journal-title":"Acta Biomater."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Liu, Z., Wang, Q., Zhang, J., Qi, S., Duan, Y., and Li, C. (2023). The Mechanotransduction Signaling Pathways in the Regulation of Osteogenesis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814326"},{"key":"ref_53","first-page":"221","article-title":"The Molecular Basis of Bone Mechanotransduction","volume":"16","author":"Yavropoulou","year":"2016","journal-title":"J. Musculoskelet. Neuronal Interact."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Li, R., Liang, L., Dou, Y., Huang, Z., Mo, H., Wang, Y., and Yu, B. (2015). Mechanical Strain Regulates Osteogenic and Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells. Biomed. Res. Int., 2015.","DOI":"10.1155\/2015\/873251"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Lafuente-Gracia, L., Borgiani, E., Nasello, G., and Geris, L. (2021). Towards in Silico Models of the Inflammatory Response in Bone Fracture Healing. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.703725"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Maruyama, M., Rhee, C., Utsunomiya, T., Zhang, N., Ueno, M., Yao, Z., and Goodman, S.B. (2020). Modulation of the Inflammatory Response and Bone Healing. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00386"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3563","DOI":"10.2147\/JIR.S423819","article-title":"Macrophage Polarization and the Regulation of Bone Immunity in Bone Homeostasis","volume":"16","author":"Hu","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Chen, K., Jiao, Y., Liu, L., Huang, M., He, C., He, W., Hou, J., Yang, M., Luo, X., and Li, C. (2020). Communications Between Bone Marrow Macrophages and Bone Cells in Bone Remodeling. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.598263"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1055\/s-0041-1732334","article-title":"Bone Healing and Inflammation: Principles of Fracture and Repair","volume":"35","author":"ElHawary","year":"2021","journal-title":"Semin. Plast. Surg."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.bone.2016.02.020","article-title":"Inflammation, Fracture and Bone Repair","volume":"86","author":"Loi","year":"2016","journal-title":"Bone"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Maruyama, M., Moeinzadeh, S., Guzman, R.A., Zhang, N., Storaci, H.W., Utsunomiya, T., Lui, E., Huang, E.E., Rhee, C., and Gao, Q. (2021). The Efficacy of Lapine Preconditioned or Genetically Modified IL4 Over-Expressing Bone Marrow-Derived Mesenchymal Stromal Cells in Corticosteroid-Associated Osteonecrosis of the Femoral Head in Rabbits. Biomaterials, 275.","DOI":"10.1016\/j.biomaterials.2021.120972"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"117327","DOI":"10.1016\/j.bone.2024.117327","article-title":"Innate Immune Response to Bone Fracture Healing","volume":"190","author":"Burgan","year":"2025","journal-title":"Bone"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Houschyar, K.S., Tapking, C., Borrelli, M.R., Popp, D., Duscher, D., Maan, Z.N., Chelliah, M.P., Li, J., Harati, K., and Wallner, C. (2018). Wnt Pathway in Bone Repair and Regeneration\u2013What Do We Know So Far. Front. Cell Dev. Biol., 6.","DOI":"10.3389\/fcell.2018.00170"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41422-023-00918-9","article-title":"The Roles and Regulatory Mechanisms of TGF-\u03b2 and BMP Signaling in Bone and Cartilage Development, Homeostasis and Disease","volume":"34","author":"Wu","year":"2024","journal-title":"Cell Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1089\/ten.teb.2013.0204","article-title":"The Roles of Bone Morphogenetic Proteins and Their Signaling in the Osteogenesis of Adipose-Derived Stem Cells","volume":"20","author":"Zhang","year":"2014","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"115472","DOI":"10.1016\/j.bone.2020.115472","article-title":"Bone Morphogenetic Protein Receptors: Structure, Function and Targeting by Selective Small Molecule Kinase Inhibitors","volume":"138","author":"Williams","year":"2020","journal-title":"Bone"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.2741\/2296","article-title":"Signaling and Transcriptional Regulation in Osteoblast Commitment and Differentiation","volume":"12","author":"Huang","year":"2007","journal-title":"Front. Biosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1007\/s00198-011-1728-5","article-title":"Runx2 Promotes Both Osteoblastogenesis and Novel Osteoclastogenic Signals in ST2 Mesenchymal Progenitor Cells","volume":"23","author":"Baniwal","year":"2012","journal-title":"Osteoporos. Int."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Kushchayeva, Y., Pestun, I., Kushchayev, S., Radzikhovska, N., and Lewiecki, E.M. (2022). Advancement in the Treatment of Osteoporosis and the Effects on Bone Healing. J. Clin. Med., 11.","DOI":"10.3390\/jcm11247477"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1002\/jor.25452","article-title":"Single-Cell RNAseq Provides Insight into Altered Immune Cell Populations in Human Fracture Nonunions","volume":"41","author":"Avin","year":"2023","journal-title":"J. Orthop. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/s12967-016-1019-1","article-title":"Biomarkers of Inflammation and Innate Immunity in Atrophic Nonunion Fracture","volume":"14","author":"Cobraiville","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1002\/jbmr.2422","article-title":"Macrophages Promote Osteoblastic Differentiation In-Vivo: Implications in Fracture Repair and Bone Homeostasis","volume":"30","author":"Vi","year":"2015","journal-title":"J. Bone Min. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.bone.2015.10.019","article-title":"Macrophages in Bone Fracture Healing: Their Essential Role in Endochondral Ossification","volume":"106","author":"Schlundt","year":"2018","journal-title":"Bone"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.biomaterials.2014.10.017","article-title":"Sequential Delivery of Immunomodulatory Cytokines to Facilitate the M1-to-M2 Transition of Macrophages and Enhance Vascularization of Bone Scaffolds","volume":"37","author":"Spiller","year":"2015","journal-title":"Biomaterials"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1097\/shk.0b013e3180556a0b","article-title":"The Role of C5a in the Innate Immune Response after Experimental Blunt Chest Trauma","volume":"29","author":"Flierl","year":"2008","journal-title":"Shock"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1002\/jor.21299","article-title":"Experimental Blunt Chest Trauma Impairs Fracture Healing in Rats","volume":"29","author":"Recknagel","year":"2011","journal-title":"J. Orthop. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1097\/TA.0b013e318278956d","article-title":"Systemic Inflammation Induced by a Thoracic Trauma Alters the Cellular Composition of the Early Fracture Callus","volume":"74","author":"Recknagel","year":"2013","journal-title":"J. Trauma. Acute Care Surg."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3066","DOI":"10.1016\/j.jbiomech.2008.06.038","article-title":"Mechanical Induction of Critically Delayed Bone Healing in Sheep: Radiological and Biomechanical Results","volume":"41","author":"Schell","year":"2008","journal-title":"J. Biomech."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s00441-011-1205-7","article-title":"Inflammatory Phase of Bone Healing Initiates the Regenerative Healing Cascade","volume":"347","author":"Schell","year":"2012","journal-title":"Cell Tissue Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S0736-0266(01)00142-5","article-title":"Human Atrophic Fracture Non-unions Are Not Avascular","volume":"20","author":"Reed","year":"2002","journal-title":"J. Orthop. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.1007\/s11999-009-0981-9","article-title":"Levels of Expression for BMP-7 and Several BMP Antagonists May Play an Integral Role in a Fracture Nonunion: A Pilot Study","volume":"467","author":"Fajardo","year":"2009","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"110794","DOI":"10.1016\/j.mehy.2022.110794","article-title":"Bridging the Gap: Compressing Non-Unions for Proper Cellular Signaling","volume":"160","author":"Kloen","year":"2022","journal-title":"Med. Hypotheses"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1002\/jor.20794","article-title":"Altered Relative Expression of BMPs and BMP Inhibitors in Cartilaginous Areas of Human Fractures Progressing towards Nonunion","volume":"27","author":"Kwong","year":"2009","journal-title":"J. Orthop. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1097\/BOT.0b013e3181ed294c","article-title":"Matrix Metalloproteinases That Associate with and Cleave Bone Morphogenetic Protein-2 In Vitro Are Elevated in Hypertrophic Fracture Nonunion Tissue","volume":"24","author":"Fajardo","year":"2010","journal-title":"J. Orthop. Trauma"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/j.mayocp.2013.04.027","article-title":"Advances in Regenerative Orthopedics","volume":"88","author":"Evans","year":"2013","journal-title":"Mayo Clin. Proc."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"236231","DOI":"10.1155\/2012\/236231","article-title":"An Osteoconductive, Osteoinductive, and Osteogenic Tissue-Engineered Product for Trauma and Orthopaedic Surgery: How Far Are We?","volume":"2012","author":"Khan","year":"2012","journal-title":"Stem Cells Int."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Mayfield, C.K., Ayad, M., Lechtholz-Zey, E., Chen, Y., and Lieberman, J.R. (2022). 3D-Printing for Critical Sized Bone Defects: Current Concepts and Future Directions. Bioengineering, 9.","DOI":"10.3390\/bioengineering9110680"},{"key":"ref_88","unstructured":"Patterson, J., and Lieberman, J. (2024). Segmental defect repair and nonunion. Orthobiologics: Scientific and Clinical Solutions for Orthopaedic Surgeons, Lippincott Williams & Wilkins."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s10195-021-00582-y","article-title":"Bone Marrow Aspirate Concentrate\/Platelet-Rich Fibrin Augmentation Accelerates Healing of Aseptic Upper Limb Nonunions","volume":"22","author":"Mazzotta","year":"2021","journal-title":"J. Orthop. Traumatol."},{"key":"ref_90","first-page":"73","article-title":"Clinical Translation of a Patient-Specific Scaffold-Guided Bone Regeneration Concept in Four Cases with Large Long Bone Defects","volume":"34","author":"Laubach","year":"2022","journal-title":"J. Orthop. Transl."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1186\/s13018-022-03185-3","article-title":"Therapeutic Effect of Autologous Bone Grafting with Adjuvant Bone Morphogenetic Protein on Long Bone Nonunion: A Systematic Review and Meta-Analysis","volume":"17","author":"Xie","year":"2022","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"111711","DOI":"10.1016\/j.injury.2024.111711","article-title":"Efficacy and Safety of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) Combined with Autologous Bone for the Treatment of Long Bone Nonunion: A Report of a Prospective Case Series","volume":"55","author":"Choi","year":"2024","journal-title":"Injury"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1007\/s00590-024-04048-9","article-title":"Bone Marrow Aspirate and Bone Marrow Aspirate Concentrate: Does the Literature Support Use in Long-Bone Nonunion and Provide New Insights into Mechanism of Action?","volume":"34","author":"Moyal","year":"2024","journal-title":"Eur. J. Orthop. Surg. Traumatol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.jos.2024.10.015","article-title":"Platelet-Rich Plasma in the Treatment of Delayed Union and Nonunion Fractures: An Umbrella Meta-Analysis","volume":"30","author":"Zhu","year":"2024","journal-title":"J. Orthop. Sci."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Tanavalee, C., Ngarmukos, S., Amarase, C., Tantavisut, S., Jaruthien, N., and Tanavalee, A. (2025). A Randomized Controlled Trial of Teriparatide for Accelerating Bone Union and Improving Clinical Outcomes in Patients with Pertrochanteric Fracture Fixation. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-03720-2"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"6530624","DOI":"10.1155\/2016\/6530624","article-title":"BMP6-Engineered MSCs Induce Vertebral Bone Repair in a Pig Model: A Pilot Study","volume":"2016","author":"Pelled","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Brunello, G., Panda, S., Schiavon, L., Sivolella, S., Biasetto, L., and Del Fabbro, M. (2020). The Impact of Bioceramic Scaffolds on Bone Regeneration in Preclinical In Vivo Studies: A Systematic Review. Materials, 13.","DOI":"10.3390\/ma13071500"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Liu, T., Fang, W., Wu, G., Li, Y., Pathak, J.L., and Liu, Y. (2020). Low Dose BMP2-Doped Calcium Phosphate Graft Promotes Bone Defect Healing in a Large Animal Model. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.613891"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1016\/j.injury.2022.01.015","article-title":"A Bioactive Synthetic Membrane Improves Bone Healing in a Preclinical Nonunion Model","volume":"53","author":"DeBaun","year":"2022","journal-title":"Injury"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"eabl6242","DOI":"10.1126\/sciadv.abl6242","article-title":"Efficient Healing of Large Osseous Segmental Defects Using Optimized Chemically Modified Messenger RNA Encoding BMP-2","volume":"8","author":"Zhang","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"110777","DOI":"10.1016\/j.injury.2023.05.008","article-title":"A New Option for Bone Regeneration: A Rapid Methodology for Cellularization of Allograft with Human Bone Marrow Stromal Cells with in Vivo Bone-Forming Potential","volume":"54","author":"Dias","year":"2023","journal-title":"Injury"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e2301692","DOI":"10.1002\/adhm.202301692","article-title":"3D-Printed Osteoinductive Polymeric Scaffolds with Optimized Architecture to Repair a Sheep Metatarsal Critical-Size Bone Defect","volume":"12","author":"Garot","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_103","first-page":"208","article-title":"Bio-Integrated Scaffold Facilitates Large Bone Regeneration Dominated by Endochondral Ossification","volume":"35","author":"Sun","year":"2024","journal-title":"Bioact. Mater."},{"key":"ref_104","first-page":"1","article-title":"High-Dose Romosozumab Promoted Bone Regeneration of Critical-Size Ulnar Defect Filled with Demineralized Bone Matrix in Nonhuman Primates","volume":"54","author":"Li","year":"2025","journal-title":"J. Orthop. Transl."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Aleem, I.S., Aleem, I., Evaniew, N., Busse, J.W., Yaszemski, M., Agarwal, A., Einhorn, T., and Bhandari, M. (2016). Efficacy of Electrical Stimulators for Bone Healing: A Meta-Analysis of Randomized Sham-Controlled Trials. Sci. Rep., 6.","DOI":"10.1038\/srep31724"},{"key":"ref_106","first-page":"CD008471","article-title":"Electromagnetic Field Stimulation for Treating Delayed Union or Non-Union of Long Bone Fractures in Adults","volume":"4","author":"Griffin","year":"2011","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/j.injury.2017.05.016","article-title":"Healing of Fracture Nonunions Treated with Low-Intensity Pulsed Ultrasound (LIPUS): A Systematic Review and Meta-Analysis","volume":"48","author":"Leighton","year":"2017","journal-title":"Injury"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Leighton, R., Phillips, M., Bhandari, M., and Zura, R. (2021). Low Intensity Pulsed Ultrasound (LIPUS) Use for the Management of Instrumented, Infected, and Fragility Non-Unions: A Systematic Review and Meta-Analysis of Healing Proportions. BMC Musculoskelet Disord, 22.","DOI":"10.1186\/s12891-021-04322-5"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"TRUST Investigators Writing Group, Busse, J.W., Bhandari, M., Einhorn, T.A., Schemitsch, E., Heckman, J.D., Tornetta, P., Leung, K.-S., Heels-Ansdell, D., and Makosso-Kallyth, S. (2016). Re-Evaluation of Low Intensity Pulsed Ultrasound in Treatment of Tibial Fractures (TRUST): Randomized Clinical Trial. BMJ, 355, i5351.","DOI":"10.1136\/bmj.i5351"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.2106\/JBJS.23.00783","article-title":"WECAN Low-Intensity Pulsed Ultrasound Versus Sham in the Treatment of Operatively Managed Scaphoid Nonunions: The SNAPU Randomized Controlled Trial","volume":"106","author":"White","year":"2024","journal-title":"J. Bone Jt. Surg."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/j.injury.2020.10.036","article-title":"Reunion of Post Nail Aseptic Non-Union of Diaphyseal Femoral Fractures by Augmentation Plating, Decortication and Bone Grafting\u2013Replacement for Exchange Nailing","volume":"52","author":"Mittal","year":"2021","journal-title":"Injury"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"103462","DOI":"10.1016\/j.otsr.2022.103462","article-title":"Aseptic Humeral Shaft Nonunion","volume":"109","author":"Mouchantaf","year":"2023","journal-title":"Orthop. Traumatol. Surg. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e989","DOI":"10.5435\/JAAOS-D-24-00510","article-title":"Bone Graft and Fixation Options in the Surgical Management of Scaphoid Nonunion","volume":"33","author":"Ayalon","year":"2024","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1002\/jor.24978","article-title":"Masquelet\u2019s Induced Membrane Technique: Review of Current Concepts and Future Directions","volume":"39","author":"Alford","year":"2021","journal-title":"J. Orthop. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e106(1\u20135)","DOI":"10.1097\/OI9.0000000000000106","article-title":"The Induced Membrane Technique for Bone Defects: Basic Science, Clinical Evidence, and Technical Tips","volume":"4","author":"Hoit","year":"2021","journal-title":"OTA Int."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.cjtee.2024.04.003","article-title":"Mechanisms of the Masquelet Technique to Promote Bone Defect Repair and Its Influencing Factors","volume":"28","author":"Wu","year":"2025","journal-title":"Chin. J. Traumatol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.otsr.2020.02.015","article-title":"Induced-Membrane Treatment of Refractory Humeral Non-Union with or without Bone Defect","volume":"106","author":"Gaillard","year":"2020","journal-title":"Orthop. Traumatol. Surg. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e170","DOI":"10.1097\/OI9.0000000000000170","article-title":"Induced Membrane Technique for Acute Bone Loss and Nonunion Management of the Tibia","volume":"5","author":"Chloros","year":"2022","journal-title":"OTA Int."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1097\/BOT.0000000000002480","article-title":"Masquelet Technique for the Tibia: A Systematic Review and Meta-Analysis of Contemporary Outcomes","volume":"37","author":"Griffin","year":"2023","journal-title":"J. Orthop. Trauma"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"583.e1","DOI":"10.1016\/j.jhsa.2021.06.019","article-title":"Induced Membrane Technique for the Treatment of Infected Forearm Nonunion: A Retrospective Study","volume":"47","author":"Ma","year":"2022","journal-title":"J. Hand Surg."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0891-5520(01)00009-5","article-title":"Pathogenesis of Streptococcal and Staphylococcal Endocarditis","volume":"16","author":"Moreillon","year":"2002","journal-title":"Infect. Dis. Clin. North. Am."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.jhsa.2023.06.008","article-title":"Vascularized Bone Grafting Versus the 2-Stage Masquelet Technique for Upper-Extremity Bone Reconstruction: A Meta-Analysis","volume":"48","author":"Singh","year":"2023","journal-title":"J. Hand Surg. Am."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e342","DOI":"10.1097\/OI9.0000000000000342","article-title":"Hypertrophic Nonunion Management with Distraction Osteogenesis: A Scoping Review of the Literature","volume":"7","author":"Rouse","year":"2024","journal-title":"OTA Int."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1007\/s00402-019-03225-4","article-title":"The PRECICE Magnetic IM Compression Nail for Long Bone Nonunions: A Preliminary Report","volume":"139","author":"Fragomen","year":"2019","journal-title":"Arch. Orthop. Trauma. Surg."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1097\/BOT.0000000000001420","article-title":"Autograft, Allograft, and Bone Graft Substitutes: Clinical Evidence and Indications for Use in the Setting of Orthopaedic Trauma Surgery","volume":"33","author":"Baldwin","year":"2019","journal-title":"J. Orthop. Trauma."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1530\/EOR-24-0032","article-title":"Long Bone Uninfected Non-Union: Grafting Techniques","volume":"9","author":"Ehrnthaller","year":"2024","journal-title":"EFORT Open Rev."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s40001-021-00593-9","article-title":"Strategies for Large Bone Defect Reconstruction after Trauma, Infections or Tumour Excision: A Comprehensive Review of the Literature","volume":"26","author":"Migliorini","year":"2021","journal-title":"Eur. J. Med. Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.injury.2011.06.015","article-title":"Complications Following Autologous Bone Graft Harvesting from the Iliac Crest and Using the RIA: A Systematic Review","volume":"42","author":"Dimitriou","year":"2011","journal-title":"Injury"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.ocl.2017.03.006","article-title":"Orthobiologics in Pediatric Sports Medicine","volume":"48","author":"Bray","year":"2017","journal-title":"Orthop. Clin. North. Am."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"e441","DOI":"10.1016\/j.eats.2016.10.024","article-title":"Bone Marrow Aspirate Concentrate Harvesting and Processing Technique","volume":"6","author":"Chahla","year":"2017","journal-title":"Arthrosc. Tech."},{"key":"ref_131","first-page":"6659","article-title":"The Basic Science of Bone Marrow Aspirate Concentrate in Chondral Injuries","volume":"8","author":"Holton","year":"2016","journal-title":"Orthop. Rev."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Kim, G.B., Seo, M.-S., Park, W.T., and Lee, G.W. (2020). Bone Marrow Aspirate Concentrate: Its Uses in Osteoarthritis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093224"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"e012","DOI":"10.1097\/OI9.0000000000000012","article-title":"Bone Marrow Aspirate Concentrate with Cancellous Allograft versus Iliac Crest Bone Graft in the Treatment of Long Bone Nonunions","volume":"2","author":"Lin","year":"2019","journal-title":"OTA Int."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"S67","DOI":"10.1016\/j.injury.2020.09.029","article-title":"Treatment of Infected Tibial Non-Unions Using a BMAC and S53P4 BAG Combination for Reconstruction of Segmental Bone Defects: A Clinical Case Series","volume":"52","author":"Geurts","year":"2021","journal-title":"Injury"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"23259671211058459","DOI":"10.1177\/23259671211058459","article-title":"High Variability of Mesenchymal Stem Cells Obtained via Bone Marrow Aspirate Concentrate Compared with Traditional Bone Marrow Aspiration Technique","volume":"9","author":"Brozovich","year":"2021","journal-title":"Orthop. J. Sports Med."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1007\/s00167-022-07153-6","article-title":"Bone Marrow Aspirate Concentrate Quality Is Affected by Age and Harvest Site","volume":"31","author":"Cavallo","year":"2023","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Rodriguez, I.A., Growney Kalaf, E.A., Bowlin, G.L., and Sell, S.A. (2014). Platelet-Rich Plasma in Bone Regeneration: Engineering the Delivery for Improved Clinical Efficacy. Biomed. Res. Int., 2014.","DOI":"10.1155\/2014\/392398"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"112325","DOI":"10.1016\/j.injury.2025.112325","article-title":"Based on the Diamond Concept, Application of Platelet-Rich Plasma in the Treatment of Aseptic Femoral Shaft Nonunion: A Retrospective Controlled Study on 66 Patients","volume":"56","author":"Wang","year":"2025","journal-title":"Injury"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3062","DOI":"10.1177\/0363546515608481","article-title":"Comparison of the Cellular Composition and Cytokine-Release Kinetics of Various Platelet-Rich Plasma Preparations","volume":"43","author":"Oh","year":"2015","journal-title":"Am. J. Sports Med."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1549826","DOI":"10.1155\/2018\/1549826","article-title":"Comparative Analysis of Cellular and Growth Factor Composition in Bone Marrow Aspirate Concentrate and Platelet-Rich Plasma","volume":"2018","author":"Sugaya","year":"2018","journal-title":"Bone Marrow Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1177\/0363546511417792","article-title":"Growth Factor and Catabolic Cytokine Concentrations Are Influenced by the Cellular Composition of Platelet-Rich Plasma","volume":"39","author":"Sundman","year":"2011","journal-title":"Am. J. Sports Med."},{"key":"ref_142","first-page":"403","article-title":"Cracking the Code: Understanding ESWT\u2019s Role in Bone Fracture Healing","volume":"50","author":"Jing","year":"2025","journal-title":"J. Orthop. Transl."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1016\/j.injury.2022.09.021","article-title":"A Scoping Review of Operative and Non-Invasive Management in the Treatment of Non-Unions","volume":"53","author":"Phillips","year":"2022","journal-title":"Injury"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Gillman, C.E., and Jayasuriya, A.C. (2021). FDA-Approved Bone Grafts and Bone Graft Substitute Devices in Bone Regeneration. Mater. Sci. Eng. C Mater. Biol. Appl., 130.","DOI":"10.1016\/j.msec.2021.112466"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.biomaterials.2018.03.033","article-title":"Feasibility and Safety of Treating Non-Unions in Tibia, Femur and Humerus with Autologous, Expanded, Bone Marrow-Derived Mesenchymal Stromal Cells Associated with Biphasic Calcium Phosphate Biomaterials in a Multicentric, Non-Comparative Trial","volume":"196","author":"Rosset","year":"2019","journal-title":"Biomaterials"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"102231","DOI":"10.1016\/j.jcot.2023.102231","article-title":"Current Concepts of Bone Grafting in Trauma Surgery","volume":"43","author":"Nashi","year":"2023","journal-title":"J. Clin. Orthop. Trauma."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.jor.2025.04.008","article-title":"Bone Marrow Aspirate Concentrate (BMAC) Harvested in the Axial and Appendicular Skeleton Does Not Differ in Progenitor Cell Count: A Systematic Review and Meta-Analysis","volume":"63","author":"Dave","year":"2025","journal-title":"J. Orthop."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"101760","DOI":"10.1016\/j.bonr.2024.101760","article-title":"Orthobiologics in Delayed Union and Non-Union of Adult Long Bones Fractures: A Systematic Review","volume":"21","author":"Impieri","year":"2024","journal-title":"Bone Rep."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"905","DOI":"10.2106\/00004623-199907000-00002","article-title":"The Effect of Regional Gene Therapy with Bone Morphogenetic Protein-2-Producing Bone-Marrow Cells on the Repair of Segmental Femoral Defects in Rats","volume":"81","author":"Lieberman","year":"1999","journal-title":"JBJS"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Paulini, M., Camal Ruggieri, I.N., Ramallo, M., Alonso, M., Rodriguez-Cabello, J.C., Esbrit, P., Mardegan Issa, J.P., and Feldman, S. (2021). Recombinant Proteins-Based Strategies in Bone Tissue Engineering. Biomolecules, 12.","DOI":"10.3390\/biom12010003"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jeurceramsoc.2023.09.003","article-title":"Review on the Strategies to Improve the Mechanical Strength of Highly Porous Bone Bioceramic Scaffolds","volume":"44","author":"Miri","year":"2024","journal-title":"J. Eur. Ceram. Soc."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Percival, K.M., Paul, V., and Husseini, G.A. (2024). Recent Advancements in Bone Tissue Engineering: Integrating Smart Scaffold Technologies and Bio-Responsive Systems for Enhanced Regeneration. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25116012"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/00003086-200402000-00004","article-title":"Internal Fixation of Nonunions","volume":"419","year":"2004","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Schulze, F., Lang, A., Schoon, J., Wassilew, G.I., and Reichert, J. (2023). Scaffold Guided Bone Regeneration for the Treatment of Large Segmental Defects in Long Bones. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020325"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Farjaminejad, S., Farjaminejad, R., Hasani, M., Garcia-Godoy, F., Abdouss, M., Marya, A., Harsoputranto, A., and Jamilian, A. (2024). Advances and Challenges in Polymer-Based Scaffolds for Bone Tissue Engineering: A Path Towards Personalized Regenerative Medicine. Polymers, 16.","DOI":"10.3390\/polym16233303"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"585","DOI":"10.3390\/cimb46010038","article-title":"Harnessing Natural Polymers for Nano-Scaffolds in Bone Tissue Engineering: A Comprehensive Overview of Bone Disease Treatment","volume":"46","author":"Saurav","year":"2024","journal-title":"CIMB"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s40820-024-01557-4","article-title":"Recent Strategies and Advances in Hydrogel-Based Delivery Platforms for Bone Regeneration","volume":"17","author":"Wang","year":"2024","journal-title":"Nano-Micro Lett."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s12891-025-08365-w","article-title":"Mesenchymal Stem Cells Therapy for the Treatment of Non-Union Fractures: A Systematic Review and Meta-Analysis","volume":"26","author":"Cui","year":"2025","journal-title":"BMC Musculoskelet Disord"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Lalu, M.M., McIntyre, L., Pugliese, C., Fergusson, D., Winston, B.W., Marshall, J.C., Granton, J., and Stewart, D.J. (2012). Canadian Critical Care Trials Group Safety of Cell Therapy with Mesenchymal Stromal Cells (SafeCell): A Systematic Review and Meta-Analysis of Clinical Trials. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047559"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1111\/cas.13334","article-title":"Double-Edged Sword of Mesenchymal Stem Cells: Cancer-Promoting versus Therapeutic Potential","volume":"108","author":"Lee","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"23094990211036545","DOI":"10.1177\/23094990211036545","article-title":"Stem Cell Therapy for Fracture Non-Union: The Current Evidence from Human Studies","volume":"29","author":"Thurairajah","year":"2021","journal-title":"J. Orthop. Surg."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s40259-023-00585-7","article-title":"Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer","volume":"37","author":"Arjomandnejad","year":"2023","journal-title":"BioDrugs"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Chu, X., Xiong, Y., Lu, L., Wang, Y., Wang, J., Zeng, R., Hu, L., Yan, C., Zhao, Z., and Lin, S. (2024). Research Progress of Gene Therapy Combined with Tissue Engineering to Promote Bone Regeneration. APL Bioeng., 8.","DOI":"10.1063\/5.0200551"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.omtm.2022.11.009","article-title":"Meeting FDA Guidance Recommendations for Replication-Competent Virus and Insertional Oncogenesis Testing","volume":"28","author":"Cornetta","year":"2023","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Gallo, M.C., Elias, A., Reynolds, J., Ball, J.R., and Lieberman, J.R. (2025). Regional Gene Therapy for Bone Tissue Engineering: A Current Concepts Review. Bioengineering, 12.","DOI":"10.3390\/bioengineering12020120"},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"De Pace, R., Molinari, S., Mazzoni, E., and Perale, G. (2025). Bone Regeneration: A Review of Current Treatment Strategies. JCM, 14.","DOI":"10.3390\/jcm14061838"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1177\/15353702211052927","article-title":"Modern Approaches on Stem Cells and Scaffolding Technology for Osteogenic Differentiation and Regeneration","volume":"247","author":"Kirankumar","year":"2022","journal-title":"Exp. Biol. Med."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"5551222","DOI":"10.1155\/sci\/5551222","article-title":"Impact of Different Cell Types on the Osteogenic Differentiation Process of Mesenchymal Stem Cells","volume":"2025","author":"Wang","year":"2025","journal-title":"Stem Cells Int."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Zhao, T., Chu, Z., Ma, J., and Ouyang, L. (2022). Immunomodulation Effect of Biomaterials on Bone Formation. J. Funct. Biomater., 13.","DOI":"10.3390\/jfb13030103"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"e1900977","DOI":"10.1002\/adhm.201900977","article-title":"Controlled Growth Factor Release in 3D-Printed Hydrogels","volume":"9","author":"Wang","year":"2020","journal-title":"Adv. Heal Mater."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1177\/1947601911423031","article-title":"Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis","volume":"2","author":"Shibuya","year":"2011","journal-title":"Genes. Cancer"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1101\/gad.1653708","article-title":"Role of Platelet-Derived Growth Factors in Physiology and Medicine","volume":"22","author":"Andrae","year":"2008","journal-title":"Genes. Dev."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Cohn-Schwartz, D., Schary, Y., Yalon, E., Krut, Z., Da, X., Schwarz, E.M., Gazit, D., Pelled, G., and Gazit, Z. (2022). PTH-Induced Bone Regeneration and Vascular Modulation Are Both Dependent on Endothelial Signaling. Cells, 11.","DOI":"10.3390\/cells11050897"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1186\/s12967-023-04661-y","article-title":"Parathyroid Hormone Stimulates Bone Regeneration in an Atrophic Non-Union Model in Aged Mice","volume":"21","author":"Menger","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"RP93830","DOI":"10.7554\/eLife.93830","article-title":"Enhancing Bone Regeneration and Osseointegration Using rhPTH(1-34) and Dimeric R25CPTH(1-34) in an Osteoporotic Beagle Model","volume":"13","author":"Shin","year":"2024","journal-title":"Elife"},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Zhang, S., Ding, L., Chen, G., Zhang, J., Ge, W., and Qu, Y. (2023). Enhanced Bone Regeneration via Local Low-Dose Delivery of PTH1-34 in a Composite Hydrogel. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1209752"},{"key":"ref_177","first-page":"1839","article-title":"Simultaneous Incorporation of PTH(1-34) and Nano-Hydroxyapatite into Chitosan\/Alginate Hydrogels for Efficient Bone Regeneration","volume":"6","author":"Zou","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/jbm.b.33561","article-title":"Bone Regeneration in Critical Bone Defects Using Three-Dimensionally Printed \u03b2-Tricalcium Phosphate\/Hydroxyapatite Scaffolds Is Enhanced by Coating Scaffolds with Either Dipyridamole or BMP-2","volume":"105","author":"Ishack","year":"2017","journal-title":"J. Biomed. Mater. Res. B Appl. Biomater."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1096\/fj.14-265066","article-title":"Direct or Indirect Stimulation of Adenosine A2A Receptors Enhances Bone Regeneration as Well as Bone Morphogenetic Protein-2","volume":"29","author":"Mediero","year":"2015","journal-title":"FASEB J."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1002\/jor.24424","article-title":"Repair of Critical-Sized Long Bone Defects Using Dipyridamole-Augmented 3D-Printed Bioactive Ceramic Scaffolds","volume":"37","author":"Witek","year":"2019","journal-title":"J. Orthop. Res."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3109\/08977194.2012.656761","article-title":"FGF\/FGFR Signaling in Bone Formation: Progress and Perspectives","volume":"30","author":"Marie","year":"2012","journal-title":"Growth Factors"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.bone.2015.05.001","article-title":"Multiple Roles of Tumor Necrosis Factor-Alpha in Fracture Healing","volume":"78","author":"Karnes","year":"2015","journal-title":"Bone"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.stemcr.2017.01.005","article-title":"Healing of a Large Long-Bone Defect through Serum-Free In Vitro Priming of Human Periosteum-Derived Cells","volume":"8","author":"Bolander","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"eaay1240","DOI":"10.1126\/sciadv.aay1240","article-title":"Heparin-Mediated Delivery of Bone Morphogenetic Protein-2 Improves Spatial Localization of Bone Regeneration","volume":"6","author":"Hettiaratchi","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.1007\/s11999-015-4312-z","article-title":"Hydrogel-Based Delivery of rhBMP-2 Improves Healing of Large Bone Defects Compared with Autograft","volume":"473","author":"Krishnan","year":"2015","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"411","DOI":"10.3415\/VCOT-14-03-0036","article-title":"BMP-2 Delivered from a Self-Crosslinkable CaP\/Hydrogel Construct Promotes Bone Regeneration in a Critical-Size Segmental Defect Model of Non-Union in Dogs","volume":"27","author":"Minier","year":"2014","journal-title":"Vet. Comp. Orthop. Traumatol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s00776-012-0196-x","article-title":"Repair of Critical Long Bone Defects Using Frozen Bone Allografts Coated with an rhBMP-2-Retaining Paste","volume":"17","author":"Yasuda","year":"2012","journal-title":"J. Orthop. Sci."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1007\/s11095-017-2147-x","article-title":"Formulation, Delivery and Stability of Bone Morphogenetic Proteins for Effective Bone Regeneration","volume":"34","author":"Jiskoot","year":"2017","journal-title":"Pharm. Res."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s00264-007-0418-6","article-title":"A Comprehensive Clinical Review of Recombinant Human Bone Morphogenetic Protein-2 (INFUSE Bone Graft)","volume":"31","author":"McKay","year":"2007","journal-title":"Int. Orthop."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1089\/ten.tea.2010.0555","article-title":"High Doses of Bone Morphogenetic Protein 2 Induce Structurally Abnormal Bone and Inflammation in Vivo","volume":"17","author":"Zara","year":"2011","journal-title":"Tissue Eng. Part A"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1001\/jama.2009.956","article-title":"Prevalence, Complications, and Hospital Charges Associated with Use of Bone-Morphogenetic Proteins in Spinal Fusion Procedures","volume":"302","author":"Cahill","year":"2009","journal-title":"JAMA"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1097\/01.brs.0000245863.52371.c2","article-title":"Increased Swelling Complications Associated with Off-Label Usage of rhBMP-2 in the Anterior Cervical Spine","volume":"31","author":"Smucker","year":"2006","journal-title":"Spine"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.2106\/JBJS.L.01483","article-title":"Cancer Risk after Use of Recombinant Bone Morphogenetic Protein-2 for Spinal Arthrodesis","volume":"95","author":"Carragee","year":"2013","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.biomaterials.2010.09.008","article-title":"The Effect of Immobilization of Heparin and Bone Morphogenic Protein-2 (BMP-2) to Titanium Surfaces on Inflammation and Osteoblast Function","volume":"32","author":"Kim","year":"2011","journal-title":"Biomaterials"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"145217","DOI":"10.1016\/j.gene.2020.145217","article-title":"A Biomimetic Collagen-Bone Granule-Heparan Sulfate Combination Scaffold for BMP2 Delivery","volume":"769","author":"Lee","year":"2021","journal-title":"Gene"},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Kim, T.-H., Yun, Y.-P., Park, Y.-E., Lee, S.-H., Yong, W., Kundu, J., Jung, J.W., Shim, J.-H., Cho, D.-W., and Kim, S.E. (2014). In Vitro and in Vivo Evaluation of Bone Formation Using Solid Freeform Fabrication-Based Bone Morphogenic Protein-2 Releasing PCL\/PLGA Scaffolds. Biomed. Mater., 9.","DOI":"10.1088\/1748-6041\/9\/2\/025008"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"eabh4302","DOI":"10.1126\/sciadv.abh4302","article-title":"Engineered Bridge Protein with Dual Affinity for Bone Morphogenetic Protein-2 and Collagen Enhances Bone Regeneration for Spinal Fusion","volume":"7","author":"Briquez","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3109\/17453674.2013.773123","article-title":"Augmentation of Autologous Bone Graft by a Combination of Bone Morphogenic Protein and Bisphosphonate Increased Both Callus Volume and Strength","volume":"84","author":"Bosemark","year":"2013","journal-title":"Acta Orthop."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1002\/jor.22599","article-title":"Influence of Systemic Bisphosphonate Treatment on Mechanical Properties of BMP-Induced Calluses in a Rat Fracture Model: Comparison of Three-Point Bending and Twisting Test","volume":"32","author":"Bosemark","year":"2014","journal-title":"J. Orthop. Res."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1002\/jor.22132","article-title":"BMP-2 but Not VEGF or PDGF in Fibrin Matrix Supports Bone Healing in a Delayed-union Rat Model","volume":"30","author":"Kaipel","year":"2012","journal-title":"J. Orthop. Res."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1089\/ten.tea.2020.0382","article-title":"Regional Gene Therapy with Transduced Human Cells: The Influence of \u201cCell Dose\u201d on Bone Repair","volume":"27","author":"Ihn","year":"2021","journal-title":"Tissue Eng. Part A"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.ymthe.2022.10.007","article-title":"IL-1Ra Gene Transfer Potentiates BMP2-Mediated Bone Healing by Redirecting Osteogenesis toward Endochondral Ossification","volume":"31","author":"Panos","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.bone.2016.06.013","article-title":"The Roles of Vascular Endothelial Growth Factor in Bone Repair and Regeneration","volume":"91","author":"Hu","year":"2016","journal-title":"Bone"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.actbio.2021.11.037","article-title":"Controlled pVEGF Delivery via a Gene-Activated Matrix Comprised of a Peptide-Modified Non-Viral Vector and a Nanofibrous Scaffold for Skin Wound Healing","volume":"140","author":"He","year":"2022","journal-title":"Acta Biomater."},{"key":"ref_205","doi-asserted-by":"crossref","unstructured":"Orth, M., Fritz, T., Stutz, J., Scheuer, C., Ganse, B., Bullinger, Y., Lee, J.S., Murphy, W.L., Laschke, M.W., and Menger, M.D. (2022). Local Application of Mineral-Coated Microparticles Loaded with VEGF and BMP-2 Induces the Healing of Murine Atrophic Non-Unions. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.809397"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41536-023-00276-5","article-title":"PDGF Inhibits BMP2-Induced Bone Healing","volume":"8","author":"Novak","year":"2023","journal-title":"NPJ Regen. Med."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1177\/1071100719851468","article-title":"Recombinant Human Platelet-Derived Growth Factor BB in Combination With a Beta-Tricalcium Phosphate (rhPDGF-BB\/\u03b2-TCP)-Collagen Matrix as an Alternative to Autograft","volume":"40","author":"Daniels","year":"2019","journal-title":"Foot Ankle Int."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.2106\/JBJS.K.01422","article-title":"Recombinant Human Platelet-Derived Growth Factor-BB and Beta-Tricalcium Phosphate (rhPDGF-BB\/\u03b2-TCP): An Alternative to Autogenous Bone Graft","volume":"95","author":"DiGiovanni","year":"2013","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1002\/jor.20453","article-title":"Accelerated Fracture Healing in the Geriatric, Osteoporotic Rat with Recombinant Human Platelet-derived Growth Factor-bb and an Injectable Beta-tricalcium Phosphate\/Collagen Matrix","volume":"26","author":"Hollinger","year":"2008","journal-title":"J. Orthop. Res."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1002\/jor.25847","article-title":"A rhPDGF-BB\/Bovine Type I Collagen\/\u03b2-TCP Mixture for the Treatment of Critically Sized Non-union Tibial Defects: An in Vivo Study in Rabbits","volume":"42","author":"Nayak","year":"2024","journal-title":"J. Orthop. Res."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1007\/s00198-023-06809-4","article-title":"The Effect of Intermittent Parathyroid Hormone on Bone Lengthening: Current Evidence to Inform Future Effective Interventions","volume":"34","author":"Kitcharanant","year":"2023","journal-title":"Osteoporos. Int."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1359\/jbmr.1999.14.6.960","article-title":"Intermittent Parathyroid Hormone (1-34) Treatment Increases Callus Formation and Mechanical Strength of Healing Rat Fractures","volume":"14","author":"Andreassen","year":"1999","journal-title":"J. Bone Min. Res."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s11420-009-9109-8","article-title":"Recent Advances Toward the Clinical Application of PTH (1-34) in Fracture Healing","volume":"5","author":"Cipriano","year":"2009","journal-title":"HSS J."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1097\/00003086-199909000-00033","article-title":"Parathyroid Hormone Enhances Fracture Healing. A Preliminary Report","volume":"366","author":"Holzer","year":"1999","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_215","doi-asserted-by":"crossref","unstructured":"Kumabe, Y., Lee, S.Y., Waki, T., Iwakura, T., Takahara, S., Arakura, M., Kuroiwa, Y., Fukui, T., Matsumoto, T., and Matsushita, T. (2017). Triweekly Administration of Parathyroid Hormone (1\u201334) Accelerates Bone Healing in a Rat Refractory Fracture Model. BMC Musculoskelet. Disord., 18.","DOI":"10.1186\/s12891-017-1917-2"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"e800","DOI":"10.6061\/clinics\/2019\/e800","article-title":"The Effectiveness and Safety of Parathyroid Hormone in Fracture Healing: A Meta-Analysis","volume":"74","author":"Hong","year":"2019","journal-title":"Clinics"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1007\/s00198-021-05847-0","article-title":"Effectiveness of Parathyroid Hormone (PTH) Analogues on Fracture Healing: A Meta-Analysis","volume":"32","author":"Eastman","year":"2021","journal-title":"Osteoporos. Int."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1016\/j.bmcl.2009.01.059","article-title":"Discovery of CP-533536: An EP2 Receptor Selective Prostaglandin E2 (PGE2) Agonist That Induces Local Bone Formation","volume":"19","author":"Cameron","year":"2009","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1517\/13543780902893051","article-title":"Prostaglandin EP2 and EP4 Receptor Agonists in Bone Formation and Bone Healing: In Vivo and in Vitro Evidence","volume":"18","author":"Graham","year":"2009","journal-title":"Expert. Opin. Investig. Drugs"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s00264-007-0406-x","article-title":"Prostaglandin E2 Receptors in Bone Formation","volume":"31","author":"Li","year":"2007","journal-title":"Int. Orthop."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1002\/art.30151","article-title":"Nanogel-Based Scaffold Delivery of Prostaglandin E(2) Receptor-Specific Agonist in Combination with a Low Dose of Growth Factor Heals Critical-Size Bone Defects in Mice","volume":"63","author":"Kamolratanakul","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/jgm.1148","article-title":"Retroviral-Based Gene Therapy with Cyclooxygenase-2 Promotes the Union of Bony Callus Tissues and Accelerates Fracture Healing in the Rat","volume":"10","author":"Rundle","year":"2008","journal-title":"J. Gene Med."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1021\/acsbiomaterials.4c01613","article-title":"Immunomodulation in Bone Tissue Engineering: Recent Advancements in Scaffold Design and Biological Modifications for Enhanced Regeneration","volume":"11","author":"Abedi","year":"2025","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"917","DOI":"10.2147\/IJN.S393080","article-title":"The 3D-Printed Ordered Bredigite Scaffold Promotes Pro-Healing of Critical-Sized Bone Defects by Regulating Macrophage Polarization","volume":"18","author":"Xuan","year":"2023","journal-title":"Int. J. Nanomed."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"173090","DOI":"10.1016\/j.ejphar.2020.173090","article-title":"Macrophage M1\/M2 Polarization","volume":"877","author":"Yunna","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_226","doi-asserted-by":"crossref","unstructured":"Mahon, O.R., Browe, D.C., Gonzalez-Fernandez, T., Pitacco, P., Whelan, I.T., Von Euw, S., Hobbs, C., Nicolosi, V., Cunningham, K.T., and Mills, K.H.G. (2020). Nano-Particle Mediated M2 Macrophage Polarization Enhances Bone Formation and MSC Osteogenesis in an IL-10 Dependent Manner. Biomaterials, 239.","DOI":"10.1016\/j.biomaterials.2020.119833"},{"key":"ref_227","doi-asserted-by":"crossref","unstructured":"Xiong, S., Zhang, Y., Zeng, J., Zhou, J., Liu, S., Wei, P., Liu, H., Yi, F., Wan, Z., and Xiong, L. (2024). DLP Fabrication of HA Scaffold with Customized Porous Structures to Regulate Immune Microenvironment and Macrophage Polarization for Enhancing Bone Regeneration. Mater. Today Bio, 24.","DOI":"10.1016\/j.mtbio.2023.100929"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"1807356","DOI":"10.1002\/adfm.201807356","article-title":"3D Molecularly Functionalized Cell-Free Biomimetic Scaffolds for Osteochondral Regeneration","volume":"29","author":"Li","year":"2019","journal-title":"Adv. Funct. Mater."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.bone.2015.12.052","article-title":"Combination Therapy with BMP-2 and a Systemic RANKL Inhibitor Enhances Bone Healing in a Mouse Critical-Sized Femoral Defect","volume":"84","author":"Bougioukli","year":"2016","journal-title":"Bone"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.biomaterials.2011.09.050","article-title":"Local Suppression of Pro-Inflammatory Cytokines and the Effects in BMP-2-Induced Bone Regeneration","volume":"33","author":"Ratanavaraporn","year":"2012","journal-title":"Biomaterials"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1016\/j.injury.2011.06.008","article-title":"Bioresorbability, Porosity and Mechanical Strength of Bone Substitutes: What Is Optimal for Bone Regeneration?","volume":"42","author":"Hannink","year":"2011","journal-title":"Injury"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.tibtech.2012.07.005","article-title":"Recent Advances in Bone Tissue Engineering Scaffolds","volume":"30","author":"Bose","year":"2012","journal-title":"Trends Biotechnol."},{"key":"ref_233","doi-asserted-by":"crossref","unstructured":"Eliaz, N., and Metoki, N. (2017). Calcium Phosphate Bioceramics: A Review of Their History, Structure, Properties, Coating Technologies and Biomedical Applications. Materials, 10.","DOI":"10.3390\/ma10040334"},{"key":"ref_234","doi-asserted-by":"crossref","unstructured":"Chinnasami, H., Dey, M.K., and Devireddy, R. (2023). Three-Dimensional Scaffolds for Bone Tissue Engineering. Bioengineering, 10.","DOI":"10.3390\/bioengineering10070759"},{"key":"ref_235","doi-asserted-by":"crossref","unstructured":"Farazin, A., and Darghiasi, S.F. (2025). Advanced Polymeric Scaffolds for Bone Tissue Regeneration. Explor. BioMat-X, 2.","DOI":"10.37349\/ebmx.2025.101340"},{"key":"ref_236","doi-asserted-by":"crossref","unstructured":"Filippi, M., Born, G., Chaaban, M., and Scherberich, A. (2020). Natural Polymeric Scaffolds in Bone Regeneration. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00474"},{"key":"ref_237","doi-asserted-by":"crossref","unstructured":"Da Cunha, M.R., Maia, F.L.M., Iatecola, A., Massimino, L.C., Plepis, A.M.d.G., Martins, V.d.C.A., Da Rocha, D.N., Mariano, E.D., Hirata, M.C., and Ferreira, J.R.M. (2023). In Vivo Evaluation of Collagen and Chitosan Scaffold, Associated or Not with Stem Cells, in Bone Repair. J. Funct. Biomater., 14.","DOI":"10.3390\/jfb14070357"},{"key":"ref_238","first-page":"35","article-title":"Differential Degradation Rate and Underlying Mechanism of a Collagen\/Chitosan Complex in Subcutis, Spinal Cord and Brain Tissues of Rat","volume":"29","author":"Fu","year":"2018","journal-title":"J. Mater. Sci: Mater. Med."},{"key":"ref_239","doi-asserted-by":"crossref","unstructured":"Azaman, F.A., Brennan Fournet, M.E., Sheikh Ab Hamid, S., Zawawi, M.S.F., Da Silva Junior, V.A., and Devine, D.M. (2023). Enhancement of Scaffold In Vivo Biodegradability for Bone Regeneration Using P28 Peptide Formulations. Pharmaceuticals, 16.","DOI":"10.3390\/ph16060876"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1021\/acscentsci.8b00170","article-title":"Modulating Viscoelasticity, Stiffness, and Degradation of Synthetic Cellular Niches via Stoichiometric Tuning of Covalent versus Dynamic Noncovalent Cross-Linking","volume":"4","author":"Tan","year":"2018","journal-title":"ACS Cent. Sci."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1021\/acs.langmuir.2c02253","article-title":"Porous Hydrogels: Present Challenges and Future Opportunities","volume":"39","author":"Foudazi","year":"2023","journal-title":"Langmuir"},{"key":"ref_242","doi-asserted-by":"crossref","unstructured":"Robinson, M., Douglas, S., and Michelle Willerth, S. (2017). Mechanically Stable Fibrin Scaffolds Promote Viability and Induce Neurite Outgrowth in Neural Aggregates Derived from Human Induced Pluripotent Stem Cells. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-06570-9"},{"key":"ref_243","doi-asserted-by":"crossref","unstructured":"Sun, S., Cui, Y., Yuan, B., Dou, M., Wang, G., Xu, H., Wang, J., Yin, W., Wu, D., and Peng, C. (2023). Drug Delivery Systems Based on Polyethylene Glycol Hydrogels for Enhanced Bone Regeneration. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1117647"},{"key":"ref_244","first-page":"3692","article-title":"Modulating Degradation of Sodium Alginate\/Bioglass Hydrogel for Improving Tissue Infiltration and Promoting Wound Healing","volume":"6","author":"Zhang","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1089\/ten.tea.2011.0076","article-title":"Optimally Porous and Biomechanically Compatible Scaffolds for Large-Area Bone Regeneration","volume":"18","author":"Amini","year":"2012","journal-title":"Tissue Eng. Part A"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1089\/ten.tea.2012.0057","article-title":"Guided Bone Regeneration in Long-Bone Defects with a Structural Hydroxyapatite Graft and Collagen Membrane","volume":"19","author":"Guda","year":"2013","journal-title":"Tissue Eng. Part A"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"S72","DOI":"10.1016\/j.injury.2020.07.040","article-title":"Synthetic and Bone Tissue Engineering Graft Substitutes: What Is the Future?","volume":"52","author":"Valtanen","year":"2021","journal-title":"Injury"},{"key":"ref_248","doi-asserted-by":"crossref","unstructured":"Cabrera Pereira, A., Tovar, N., Nayak, V.V., Mijares, D.Q., Smay, J.E., Torroni, A., Flores, R.L., and Witek, L. (2024). Direct Inkjet Writing Type 1 Bovine Collagen\/\u0392-tricalcium Phosphate Scaffolds for Bone Regeneration. J. Biomed. Mater. Res., 112.","DOI":"10.1002\/jbm.b.35347"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1002\/term.2733","article-title":"Form and Functional Repair of Long Bone Using 3D-printed Bioactive Scaffolds","volume":"12","author":"Tovar","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"4830","DOI":"10.1039\/D5BM00824G","article-title":"3D Printed Bioceramic Scaffolds with Fully Interconnected Channel Networks for Enhanced Vascularized Bone Regeneration","volume":"13","author":"Zhang","year":"2025","journal-title":"Biomater. Sci."},{"key":"ref_251","doi-asserted-by":"crossref","unstructured":"Wang, X., Nie, Z., Chang, J., Lu, M.L., and Kang, Y. (2021). Multiple Channels with Interconnected Pores in a Bioceramic Scaffold Promote Bone Tissue Formation. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-00024-z"},{"key":"ref_252","first-page":"413","article-title":"3D Printed Pore Morphology Mediates Bone Marrow Stem Cell Behaviors via RhoA\/ROCK2 Signaling Pathway for Accelerating Bone Regeneration","volume":"26","author":"Lu","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1021\/acsami.3c12575","article-title":"Piezoelectrically and Topographically Engineered Scaffolds for Accelerating Bone Regeneration","volume":"16","author":"Joo","year":"2024","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"4339","DOI":"10.2147\/IJN.S378422","article-title":"The Osteogenic Role of Barium Titanate\/Polylactic Acid Piezoelectric Composite Membranes as Guiding Membranes for Bone Tissue Regeneration","volume":"17","author":"Dai","year":"2022","journal-title":"Int. J. Nanomed."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"11850","DOI":"10.1039\/D5TC00628G","article-title":"Piezoelectric Composites with BaTiO3 NPs as Guiding Membranes: Reconstructing the Bioelectric Microenvironment for Enhanced Bone Regeneration","volume":"13","author":"Tian","year":"2025","journal-title":"J. Mater. Chem. C"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"2041731418776819","DOI":"10.1177\/2041731418776819","article-title":"Bone Substitutes: A Review of Their Characteristics, Clinical Use, and Perspectives for Large Bone Defects Management","volume":"9","author":"Keller","year":"2018","journal-title":"J. Tissue Eng."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.carbpol.2014.08.008","article-title":"Three-Dimensional Electrospun Polycaprolactone (PCL)\/Alginate Hybrid Composite Scaffolds","volume":"114","author":"Kim","year":"2014","journal-title":"Carbohydr. Polym."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"108161","DOI":"10.1016\/j.matdes.2019.108161","article-title":"Material-Based Therapy for Bone Nonunion","volume":"183","author":"Leng","year":"2019","journal-title":"Mater. Des."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.1039\/D3TB00097D","article-title":"Degradation Products of Crosslinked Silk Fibroin Scaffolds Modulate the Immune Response but Not Cell Toxicity","volume":"11","author":"Sapudom","year":"2023","journal-title":"J. Mater. Chem. B"},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/jor.25658","article-title":"Optimal Delivery of Endothelial Progenitor Cells in a Rat Model of Critical-size Bone Defects","volume":"42","author":"Godbout","year":"2024","journal-title":"J. Orthop. Res."},{"key":"ref_261","first-page":"954","article-title":"Bone Mesenchymal Stem Cells Co-Expressing VEGF and BMP-6 Genes to Combat Avascular Necrosis of the Femoral Head","volume":"15","author":"Liao","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"4300","DOI":"10.1016\/j.biomaterials.2008.07.030","article-title":"Porous Collagen-Apatite Nanocomposite Foams as Bone Regeneration Scaffolds","volume":"29","author":"Pek","year":"2008","journal-title":"Biomaterials"},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1097\/BOT.0000000000002711","article-title":"Tibial Plateau Fracture Surgical Care Using Standardized Protocols Over Time: A Single Center\u2019s Longitudinal View","volume":"37","author":"Schwartz","year":"2023","journal-title":"J. Orthop. Trauma."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1021\/bp010070p","article-title":"Degradation of Partially Oxidized Alginate and Its Potential Application for Tissue Engineering","volume":"17","author":"Bouhadir","year":"2001","journal-title":"Biotechnol. Prog."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1089\/ten.tec.2015.0452","article-title":"Biofabrication of 3D Alginate-Based Hydrogel for Cancer Research: Comparison of Cell Spreading, Viability, and Adhesion Characteristics of Colorectal HCT116 Tumor Cells","volume":"22","author":"Ivanovska","year":"2016","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"5241","DOI":"10.1016\/j.biomaterials.2011.03.063","article-title":"Effects of Protein Dose and Delivery System on BMP-Mediated Bone Regeneration","volume":"32","author":"Boerckel","year":"2011","journal-title":"Biomaterials"},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"4390","DOI":"10.1016\/j.actbio.2014.06.015","article-title":"Oxidized Alginate Hydrogels for Bone Morphogenetic Protein-2 Delivery in Long Bone Defects","volume":"10","author":"Priddy","year":"2014","journal-title":"Acta Biomater."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.addr.2012.03.016","article-title":"Silk Constructs for Delivery of Musculoskeletal Therapeutics","volume":"64","author":"Meinel","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"1706754","DOI":"10.1002\/adma.201706754","article-title":"Tissue Mimicry in Morphology and Composition Promotes Hierarchical Matrix Remodeling of Invading Stem Cells in Osteochondral and Meniscus Scaffolds","volume":"30","author":"Stuckensen","year":"2018","journal-title":"Adv. Mater."},{"key":"ref_270","doi-asserted-by":"crossref","unstructured":"Deininger, C., Wagner, A., Heimel, P., Salzer, E., Vila, X.M., Wei\u00dfenbacher, N., Grillari, J., Redl, H., Wichlas, F., and Freude, T. (2021). Enhanced BMP-2-Mediated Bone Repair Using an Anisotropic Silk Fibroin Scaffold Coated with Bone-like Apatite. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010283"},{"key":"ref_271","doi-asserted-by":"crossref","unstructured":"Feng, Y., Guo, W., Hu, L., Yi, X., and Tang, F. (2022). Application of Hydrogels as Sustained-Release Drug Carriers in Bone Defect Repair. Polymers, 14.","DOI":"10.3390\/polym14224906"},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.jsps.2019.08.001","article-title":"Thermo-Sensitive Hydrogels for Delivering Biotherapeutic Molecules: A Review","volume":"27","author":"Huang","year":"2019","journal-title":"Saudi Pharm. J."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"878","DOI":"10.7150\/thno.22072","article-title":"Sustained Release of Immunosuppressant by Nanoparticle-Anchoring Hydrogel Scaffold Improved the Survival of Transplanted Stem Cells and Tissue Regeneration","volume":"8","author":"Li","year":"2018","journal-title":"Theranostics"},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1080\/09205063.2020.1800907","article-title":"Design and Investigation of Salecan\/Chitosan Hydrogel Formulations with Improved Antibacterial Performance and 3D Cell Culture Function","volume":"31","author":"Fan","year":"2020","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_275","doi-asserted-by":"crossref","unstructured":"Whitehead, J., Griffin, K.H., Gionet-Gonzales, M., Vorwald, C.E., Cinque, S.E., and Leach, J.K. (2021). Hydrogel Mechanics Are a Key Driver of Bone Formation by Mesenchymal Stromal Cell Spheroids. Biomaterials, 269.","DOI":"10.1016\/j.biomaterials.2020.120607"},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1089\/ten.tec.2022.0040","article-title":"Viscoelastic Biomaterials for Tissue Regeneration","volume":"28","author":"Wu","year":"2022","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_277","doi-asserted-by":"crossref","unstructured":"Li, J., Wang, W., Li, M., Song, P., Lei, H., Gui, X., Zhou, C., and Liu, L. (2021). Biomimetic Methacrylated Gelatin Hydrogel Loaded With Bone Marrow Mesenchymal Stem Cells for Bone Tissue Regeneration. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.770049"},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1007\/s00109-019-01822-9","article-title":"Bone Allografts Combined with Adipose-Derived Stem Cells in an Optimized Cell\/Volume Ratio Showed Enhanced Osteogenesis and Angiogenesis in a Murine Femur Defect Model","volume":"97","author":"Wagner","year":"2019","journal-title":"J. Mol. Med."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"5051","DOI":"10.1016\/j.biomaterials.2010.03.024","article-title":"The Effect of 3D Hydrogel Scaffold Modulus on Osteoblast Differentiation and Mineralization Revealed by Combinatorial Screening","volume":"31","author":"Chatterjee","year":"2010","journal-title":"Biomaterials"},{"key":"ref_280","doi-asserted-by":"crossref","unstructured":"McBeth, C., Lauer, J., Ottersbach, M., Campbell, J., Sharon, A., and Sauer-Budge, A.F. (2017). 3D Bioprinting of GelMA Scaffolds Triggers Mineral Deposition by Primary Human Osteoblasts. Biofabrication, 9.","DOI":"10.1088\/1758-5090\/aa53bd"},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1111\/j.1538-7836.2010.04164.x","article-title":"A Local Increase in Red Blood Cell Aggregation Can Trigger Deep Vein Thrombosis: Evidence Based on Quantitative Cellular Ultrasound Imaging","volume":"9","author":"Yu","year":"2011","journal-title":"J. Thromb. Haemost."},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.biomaterials.2015.08.045","article-title":"Synthesis, Properties, and Biomedical Applications of Gelatin Methacryloyl (GelMA) Hydrogels","volume":"73","author":"Yue","year":"2015","journal-title":"Biomaterials"},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1016\/j.ijbiomac.2020.08.093","article-title":"Doubly Crosslinked Biodegradable Hydrogels Based on Gellan Gum and Chitosan for Drug Delivery and Wound Dressing","volume":"164","author":"Zhang","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.msec.2018.12.014","article-title":"Injectable Hydrogels from Enzyme-Catalyzed Crosslinking as BMSCs-Laden Scaffold for Bone Repair and Regeneration","volume":"96","author":"Zhang","year":"2019","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_285","doi-asserted-by":"crossref","unstructured":"Liu, X., Sun, S., Wang, N., Kang, R., Xie, L., and Liu, X. (2022). Therapeutic Application of Hydrogels for Bone-Related Diseases. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.998988"},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.reth.2023.12.010","article-title":"Advancements in Drug-Loaded Hydrogel Systems for Bone Defect Repair","volume":"25","author":"Shi","year":"2023","journal-title":"Regen. Ther."},{"key":"ref_287","doi-asserted-by":"crossref","unstructured":"Zheng, S., Zhong, H., Cheng, H., Li, X., Zeng, G., Chen, T., Zou, Y., Liu, W., and Sun, C. (2022). Engineering Multifunctional Hydrogel With Osteogenic Capacity for Critical-Size Segmental Bone Defect Repair. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.899457"},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1097\/BLO.0b013e31802e7e8f","article-title":"Will Mesenchymal Stem Cells Differentiate into Osteoblasts on Allograft?","volume":"457","author":"Rust","year":"2007","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_289","doi-asserted-by":"crossref","unstructured":"Rasch, A., Naujokat, H., Wang, F., Seekamp, A., Fuchs, S., and Kl\u00fcter, T. (2019). Evaluation of Bone Allograft Processing Methods: Impact on Decellularization Efficacy, Biocompatibility and Mesenchymal Stem Cell Functionality. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0218404"},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13287-020-1578-1","article-title":"Influence of Inflammatory Conditions Provided by Macrophages on Osteogenic Ability of Mesenchymal Stem Cells","volume":"11","author":"Bensiamar","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"37498","DOI":"10.52965\/001c.37498","article-title":"Stem Cells: A Comprehensive Review of Origins and Emerging Clinical Roles in Medical Practice","volume":"14","author":"Poliwoda","year":"2022","journal-title":"Orthop. Rev."},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1016\/j.injury.2010.09.027","article-title":"Treatment of Chondral Defects of the Knee with One Step Matrix-Assisted Technique Enhanced by Autologous Concentrated Bone Marrow: In Vitro Characterisation of Mesenchymal Stem Cells from Iliac Crest and Subchondral Bone","volume":"41","author":"Bertolini","year":"2010","journal-title":"Injury"},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1080\/14653240500319234","article-title":"Clarification of the Nomenclature for MSC: The International Society for Cellular Therapy Position Statement","volume":"7","author":"Horwitz","year":"2005","journal-title":"Cytotherapy"},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1111\/jcmm.14891","article-title":"Identification of Differentially Expressed Genes by Single-Cell Transcriptional Profiling of Umbilical Cord and Synovial Fluid Mesenchymal Stem Cells","volume":"24","author":"Jia","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"373","DOI":"10.5507\/bp.2013.078","article-title":"Comparison of Human Mesenchymal Stem Cells Derived from Dental Pulp, Bone Marrow, Adipose Tissue, and Umbilical Cord Tissue by Gene Expression","volume":"158","author":"Stanko","year":"2014","journal-title":"Biomed. Pap. Med. Fac. Univ. Palacky. Olomouc Czech Repub."},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13619-020-00047-3","article-title":"Effectiveness of Mesenchymal Stem Cell-Conditioned Medium in Bone Regeneration in Animal and Human Models: A Systematic Review and Meta-Analysis","volume":"9","author":"Linero","year":"2020","journal-title":"Cell Regen."},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1302\/2046-3758.57.2000587","article-title":"Mesenchymal Stem Cell Implantation in Atrophic Nonunion of the Long Bones: A Translational Study","volume":"5","author":"Ismail","year":"2016","journal-title":"Bone Jt. Res."},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"839","DOI":"10.4252\/wjsc.v14.i12.839","article-title":"Optimal Concentration of Mesenchymal Stem Cells for Fracture Healing in a Rat Model with Long Bone Fracture","volume":"14","author":"Kim","year":"2022","journal-title":"World J. Stem Cells"},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1089\/ten.tea.2009.0058","article-title":"Locally Applied Osteogenic Predifferentiated Progenitor Cells Are More Effective Than Undifferentiated Mesenchymal Stem Cells in the Treatment of Delayed Bone Healing","volume":"15","author":"Peters","year":"2009","journal-title":"Tissue Eng. Part A"},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/978-1-0716-2839-3_7","article-title":"Adipose-Derived Stromal Cells: Isolation, Expansion, and Differentiation","volume":"2598","author":"Buchert","year":"2023","journal-title":"Methods Mol. Biol."},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"4428","DOI":"10.1016\/j.biomaterials.2013.02.053","article-title":"Critical Size Bone Defect Reconstruction by an Autologous 3D Osteogenic-like Tissue Derived from Differentiated Adipose MSCs","volume":"34","author":"Schubert","year":"2013","journal-title":"Biomaterials"},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1002\/stem.103","article-title":"Regenerative Effects of Transplanted Mesenchymal Stem Cells in Fracture Healing","volume":"27","author":"Weis","year":"2009","journal-title":"Stem Cells"},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"725","DOI":"10.7150\/thno.39167","article-title":"Mesenchymal Stem Cell-Loaded Thermosensitive Hydroxypropyl Chitin Hydrogel Combined with a Three-Dimensional-Printed Poly(\u03b5-Caprolactone)\/Nano-Hydroxyapatite Scaffold to Repair Bone Defects via Osteogenesis, Angiogenesis and Immunomodulation","volume":"10","author":"Ji","year":"2020","journal-title":"Theranostics"},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"2041731420981672","DOI":"10.1177\/2041731420981672","article-title":"Decellularized Pulp Matrix as Scaffold for Mesenchymal Stem Cell Mediated Bone Regeneration","volume":"11","author":"Lee","year":"2020","journal-title":"J. Tissue Eng."},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/jbm.b.31805","article-title":"Calcium Phosphate Combination Biomaterials as Human Mesenchymal Stem Cell Delivery Vehicles for Bone Repair","volume":"97B","author":"Park","year":"2011","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_306","first-page":"1","article-title":"Utilizing Autologous Multipotent Mesenchymal Stromal Cells And\u03b2-Tricalcium Phosphate Scaffold in Human Bone Defects: A Prospective, Controlled Feasibility Trial","volume":"2016","author":"Filip","year":"2016","journal-title":"BioMed Res. Int."},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s13770-018-0129-7","article-title":"Mesenchymal Stem Cells of Different Origin-Seeded Bioceramic Construct in Regeneration of Bone Defect in Rabbit","volume":"15","author":"Maiti","year":"2018","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_308","first-page":"79","article-title":"Isolation, Proliferation, Characterization and in Vivo Osteogenic Potential of Bone-Marrow Derived Mesenchymal Stem Cells (rBMSC) in Rabbit Model","volume":"55","author":"Ninu","year":"2017","journal-title":"Indian. J. Exp. Biol."},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.7150\/ijms.31966","article-title":"Synthesis and Evaluation of BMMSC-Seeded BMP-6\/nHAG\/GMS Scaffolds for Bone Regeneration","volume":"16","author":"Li","year":"2019","journal-title":"Int. J. Med. Sci."},{"key":"ref_310","doi-asserted-by":"crossref","first-page":"8414715","DOI":"10.1155\/2016\/8414715","article-title":"Comparison of Osteogenesis between Adipose-Derived Mesenchymal Stem Cells and Their Sheets on Poly-\u03b5-Caprolactone\/\u03b2-Tricalcium Phosphate Composite Scaffolds in Canine Bone Defects","volume":"2016","author":"Kim","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"e12359","DOI":"10.1111\/cpr.12359","article-title":"Stem Cell-derived Exosomes: A Promising Strategy for Fracture Healing","volume":"50","author":"Hao","year":"2017","journal-title":"Cell Prolif."},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"318","DOI":"10.4252\/wjsc.v14.i5.318","article-title":"Mesenchymal Stem Cell-Derived Exosomes: A Novel and Potential Remedy for Cutaneous Wound Healing and Regeneration","volume":"14","author":"Hu","year":"2022","journal-title":"World J. Stem Cells"},{"key":"ref_313","doi-asserted-by":"crossref","unstructured":"Qin, Y., Wang, L., Gao, Z., Chen, G., and Zhang, C. (2016). Bone Marrow Stromal\/Stem Cell-Derived Extracellular Vesicles Regulate Osteoblast Activity and Differentiation In Vitro and Promote Bone Regeneration In Vivo. Sci. Rep., 6.","DOI":"10.1038\/srep21961"},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"3808674","DOI":"10.1155\/2016\/3808674","article-title":"Hijacking the Cellular Mail: Exosome Mediated Differentiation of Mesenchymal Stem Cells","volume":"2016","author":"Narayanan","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nbt.2816","article-title":"Mesenchymal stem cells: Immune evasive, not immune privileged","volume":"32","author":"Ankrum","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_316","doi-asserted-by":"crossref","unstructured":"Sanabria-de la Torre, R., Qui\u00f1ones-Vico, M.I., Fern\u00e1ndez-Gonz\u00e1lez, A., S\u00e1nchez-D\u00edaz, M., Montero-V\u00edlchez, T., Sierra-S\u00e1nchez, \u00c1., and Arias-Santiago, S. (2021). Alloreactive Immune Response Associated to Human Mesenchymal Stromal Cells Treatment: A Systematic Review. J. Clin. Med., 10.","DOI":"10.3390\/jcm10132991"},{"key":"ref_317","doi-asserted-by":"crossref","unstructured":"Corcoran, K.E., Trzaska, K.A., Fernandes, H., Bryan, M., Taborga, M., Srinivas, V., Packman, K., Patel, P.S., and Rameshwar, P. (2008). Mesenchymal Stem Cells in Early Entry of Breast Cancer into Bone Marrow. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002563"},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s12943-017-0597-8","article-title":"Mesenchymal Stem Cells: Key Players in Cancer Progression","volume":"16","author":"Ridge","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1007\/s11914-018-0459-3","article-title":"Recent Advances and Future of Gene Therapy for Bone Regeneration","volume":"16","author":"Shapiro","year":"2018","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.trsl.2021.04.009","article-title":"Gene Therapy for Bone Healing: Lessons Learned and New Approaches","volume":"236","author":"Panos","year":"2021","journal-title":"Transl. Res."},{"key":"ref_321","doi-asserted-by":"crossref","unstructured":"Watson-Levings, R.S., Palmer, G.D., Levings, P.P., Dacanay, E.A., Evans, C.H., and Ghivizzani, S.C. (2022). Gene Therapy in Orthopaedics: Progress and Challenges in Pre-Clinical Development and Translation. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.901317"},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1208\/s12248-009-9143-y","article-title":"Nonviral Gene Delivery: Principle, Limitations, and Recent Progress","volume":"11","author":"Gao","year":"2009","journal-title":"AAPS J."},{"key":"ref_323","doi-asserted-by":"crossref","first-page":"eaal3128","DOI":"10.1126\/scitranslmed.aal3128","article-title":"In Situ Bone Tissue Engineering via Ultrasound-Mediated Gene Delivery to Endogenous Progenitor Cells in Mini-Pigs","volume":"9","author":"Bez","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_324","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/s41596-019-0125-y","article-title":"Nonviral Ultrasound-Mediated Gene Delivery in Small and Large Animal Models","volume":"14","author":"Bez","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_325","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1089\/hgtb.2013.113","article-title":"Sonoporation Increases Therapeutic Efficacy of Inducible and Constitutive BMP2\/7 In Vivo Gene Delivery","volume":"25","author":"Feichtinger","year":"2014","journal-title":"Hum. Gene Ther. Methods"},{"key":"ref_326","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1038\/mt.2009.315","article-title":"Mesenchymal Stem Cells Expressing Osteogenic and Angiogenic Factors Synergistically Enhance Bone Formation in a Mouse Model of Segmental Bone Defect","volume":"18","author":"Kumar","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_327","doi-asserted-by":"crossref","first-page":"6505","DOI":"10.1016\/j.biomaterials.2011.05.059","article-title":"The Role of Adipose-Derived Stem Cells Engineered with the Persistently Expressing Hybrid Baculovirus in the Healing of Massive Bone Defects","volume":"32","author":"Lin","year":"2011","journal-title":"Biomaterials"},{"key":"ref_328","doi-asserted-by":"crossref","unstructured":"Sarkar, A., Gallo, M.C., Bell, J.A., Mayfield, C.K., Ball, J.R., Ayad, M., Lechtholz-Zey, E., Chang, S.W., Sugiyama, O., and Evseenko, D. (2025). Ex Vivo Regional Gene Therapy Compared to Recombinant BMP-2 for the Treatment of Critical-Size Bone Defects: An In Vivo Single-Cell RNA-Sequencing Study. Bioengineering, 12.","DOI":"10.3390\/bioengineering12010029"},{"key":"ref_329","first-page":"249","article-title":"Gene Therapy, Early Promises, Subsequent Problems, and Recent Breakthroughs","volume":"3","author":"Baradaran","year":"2013","journal-title":"Adv. Pharm. Bull."},{"key":"ref_330","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/sj.gt.3301166","article-title":"Genetic Enhancement of Fracture Repair: Healing of an Experimental Segmental Defect by Adenoviral Transfer of the BMP-2 Gene","volume":"7","author":"Baltzer","year":"2000","journal-title":"Gene Ther."},{"key":"ref_331","doi-asserted-by":"crossref","first-page":"96","DOI":"10.22203\/eCM.v018a09","article-title":"Use of Genetically Modified Muscle and Fat Grafts to Repair Defects in Bone and Cartilage","volume":"18","author":"Evans","year":"2009","journal-title":"Eur. Cell Mater."},{"key":"ref_332","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1038\/mt.2011.2","article-title":"Same Day\u201d Ex-Vivo Regional Gene Therapy: A Novel Strategy to Enhance Bone Repair","volume":"19","author":"Virk","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_333","doi-asserted-by":"crossref","first-page":"115032","DOI":"10.1016\/j.bone.2019.08.005","article-title":"Ex Vivo Gene Therapy Using Human Bone Marrow Cells Overexpressing BMP-2: \u201cNext-Day\u201d Gene Therapy versus Standard \u201cTwo Step\u201d Approach","volume":"128","author":"Bougioukli","year":"2019","journal-title":"Bone"},{"key":"ref_334","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/gt.2009.117","article-title":"PDGF-B Gene Therapy Accelerates Bone Engineering and Oral Implant Osseointegration","volume":"17","author":"Chang","year":"2010","journal-title":"Gene Ther."},{"key":"ref_335","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/nm1190","article-title":"Remodeling of Cortical Bone Allografts Mediated by Adherent rAAV-RANKL and VEGF Gene Therapy","volume":"11","author":"Ito","year":"2005","journal-title":"Nat. Med."},{"key":"ref_336","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1172\/JCI15153","article-title":"Synergistic Enhancement of Bone Formation and Healing by Stem Cell-Expressed VEGF and Bone Morphogenetic Protein-4","volume":"110","author":"Peng","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_337","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3171\/spi.1999.90.1.0109","article-title":"Percutaneous Spinal Fusion Using Bone Morphogenetic Protein-2 Gene Therapy","volume":"90","author":"Alden","year":"1999","journal-title":"J. Neurosurg. Spine"},{"key":"ref_338","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/sj.gt.3302176","article-title":"Simple and Effective Osteoinductive Gene Therapy by Local Injection of a Bone Morphogenetic Protein-2-Expressing Recombinant Adenoviral Vector and FK506 Mixture in Rats","volume":"11","author":"Kaihara","year":"2004","journal-title":"Gene Ther."},{"key":"ref_339","doi-asserted-by":"crossref","first-page":"118","DOI":"10.22203\/eCM.v030a09","article-title":"Rapid and Reliable Healing of Critical Size Bone Defects with Genetically Modified Sheep Muscle","volume":"30","author":"Liu","year":"2015","journal-title":"Eur. Cell Mater."},{"key":"ref_340","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.ymthe.2020.01.001","article-title":"Immune Responses to Viral Gene Therapy Vectors","volume":"28","author":"Shirley","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_341","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1089\/10430349950017220","article-title":"In Vivo Endochondral Bone Formation Using a Bone Morphogenetic Protein 2 Adenoviral Vector","volume":"10","author":"Alden","year":"1999","journal-title":"Hum. Gene Ther."},{"key":"ref_342","doi-asserted-by":"crossref","first-page":"160","DOI":"10.22203\/eCM.v040a10","article-title":"Effects of FK506 on the Healing of Diaphyseal, Critical Size Defects in the Rat Femur","volume":"40","author":"RE","year":"2020","journal-title":"Eur. Cell Mater."},{"key":"ref_343","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1038\/s41434-023-00415-z","article-title":"Biodistribution of Lentiviral Transduced Adipose-Derived Stem Cells for \u201cEx-Vivo\u201d Regional Gene Therapy for Bone Repair","volume":"30","author":"Bell","year":"2023","journal-title":"Gene Ther."},{"key":"ref_344","doi-asserted-by":"crossref","first-page":"115524","DOI":"10.1016\/j.bone.2020.115524","article-title":"Ex Vivo Regional Gene Therapy with Human Adipose-Derived Stem Cells for Bone Repair","volume":"138","author":"Vakhshori","year":"2020","journal-title":"Bone"},{"key":"ref_345","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1089\/hum.2018.054","article-title":"Lentiviral Gene Therapy for Bone Repair Using Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells","volume":"30","author":"Bougioukli","year":"2019","journal-title":"Hum. Gene Ther."},{"key":"ref_346","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1002\/jor.20229","article-title":"In Vivo Molecular Imaging of Adenoviral versus Lentiviral Gene Therapy in Two Bone Formation Models","volume":"24","author":"Feeley","year":"2006","journal-title":"J. Orthop. Res."},{"key":"ref_347","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1089\/1043034041361208","article-title":"Osteoinduction by Bone Morphogenetic Protein 2-Expressing Adenoviral Vector: Application of Biomaterial to Mask the Host Immune Response","volume":"15","author":"Sonobe","year":"2004","journal-title":"Hum. Gene Ther."},{"key":"ref_348","doi-asserted-by":"crossref","unstructured":"Bauso, L.V., La Fauci, V., Longo, C., and Calabrese, G. (2024). Bone Tissue Engineering and Nanotechnology: A Promising Combination for Bone Regeneration. Biology, 13.","DOI":"10.3390\/biology13040237"},{"key":"ref_349","doi-asserted-by":"crossref","first-page":"e70030","DOI":"10.1002\/nano.70030","article-title":"Integrating Nanotechnology With 3D Printing for Drug Delivery: Bone Regeneration and Beyond","volume":"6","author":"Siqueira","year":"2025","journal-title":"Nano Select"},{"key":"ref_350","doi-asserted-by":"crossref","unstructured":"Cui, Y., Li, N., Wu, J., Wang, X., Zhou, P., Bai, J., and Liu, Y. (2025). Navigating the Landscape of Materials-Based RNA Delivery Systems in Bone Healing. Adv. Funct. Mater., e09383.","DOI":"10.1002\/adfm.202509383"},{"key":"ref_351","doi-asserted-by":"crossref","first-page":"159","DOI":"10.59249\/HSYL8000","article-title":"Epigenetic Regulation of Bone Healing: Implications for Fracture Repair and Clinical Treatment Strategies","volume":"98","author":"Iyer","year":"2025","journal-title":"Yale J. Biol. Med."},{"key":"ref_352","doi-asserted-by":"crossref","unstructured":"Park, S.-Y., Lee, J.-K., Lee, S.-H., Kim, D.-S., Jung, J.-W., Kim, J.H., Baek, S.-W., You, S., Hwang, D.-Y., and Han, D.K. (2024). Multifunctional Vitamin D-Incorporated PLGA Scaffold with BMP\/VEGF-Overexpressed Tonsil-Derived MSC via CRISPR\/Cas9 for Bone Tissue Regeneration. Mater. Today Bio, 28.","DOI":"10.1016\/j.mtbio.2024.101254"},{"key":"ref_353","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s44174-023-00142-4","article-title":"Machine Learning Approaches to 3D Models for Drug Screening","volume":"2","author":"Sharma","year":"2024","journal-title":"Biomed. Mater. Devices"},{"key":"ref_354","doi-asserted-by":"crossref","unstructured":"Degenhart, C., Engelhardt, L., Niemeyer, F., Erne, F., Braun, B., Gebhard, F., and Sch\u00fctze, K. (2023). Computer-Based Mechanobiological Fracture Healing Model Predicts Non-Union of Surgically Treated Diaphyseal Femur Fractures. J. Clin. Med., 12.","DOI":"10.3390\/jcm12103461"},{"key":"ref_355","doi-asserted-by":"crossref","unstructured":"Donie, C., Reumann, M.K., Hartung, T., Braun, B.J., Histing, T., Endo, S., and Hirche, S. (2024, January 15\u201319). Predictive Model Development to Identify Failed Healing in Patients after Non-Union Fracture Surgery. Proceedings of the 2024 46th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Orlando, FL, USA.","DOI":"10.1109\/EMBC53108.2024.10782650"},{"key":"ref_356","doi-asserted-by":"crossref","unstructured":"Yu, H., Mu, Q., Wang, Z., Guo, Y., Zhao, J., Wang, G., Wang, Q., Meng, X., Dong, X., and Wang, S. (2025). A Study on Early Diagnosis for Fracture Non-Union Prediction Using Deep Learning and Bone Morphometric Parameters. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1547588"},{"key":"ref_357","doi-asserted-by":"crossref","first-page":"e1161","DOI":"10.1002\/ctm2.1161","article-title":"Prognostic and Therapeutic Potential of microRNAs for Fracture Healing Processes and Non-Union Fractures: A Systematic Review","volume":"13","author":"Breulmann","year":"2023","journal-title":"Clin. Transl. Med."},{"key":"ref_358","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1080\/1354750X.2021.1985171","article-title":"Predicting Fracture Healing with Blood Biomarkers: The Potential to Assess Patient Risk of Fracture Nonunion","volume":"26","author":"Chitwood","year":"2021","journal-title":"Biomarkers"},{"key":"ref_359","doi-asserted-by":"crossref","unstructured":"Ribitsch, I., Baptista, P.M., Lange-Consiglio, A., Melotti, L., Patruno, M., Jenner, F., Schnabl-Feichter, E., Dutton, L.C., Connolly, D.J., and van Steenbeek, F.G. (2020). Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00972"},{"key":"ref_360","first-page":"1345","article-title":"BMP-2 gene modified tissue-engineered bone repairing segmental tibial bone defects in goats","volume":"83","author":"Dai","year":"2003","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"ref_361","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.2106\/00004623-200310000-00010","article-title":"Allogeneic Mesenchymal Stem Cells Regenerate Bone in a Critical-Sized Canine Segmental Defect","volume":"85","author":"Arinzeh","year":"2003","journal-title":"J. Bone Jt. Surg. Am."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/11\/1457\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T11:01:57Z","timestamp":1762858917000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/11\/1457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,11]]},"references-count":361,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["pharmaceutics17111457"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17111457","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,11]]}}}