{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:05:19Z","timestamp":1792004719154,"version":"4.4.0"},"reference-count":213,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01AR085141-02"],"award-info":[{"award-number":["5R01AR085141-02"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"award":["5R01AR085141-02"],"award-info":[{"award-number":["5R01AR085141-02"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["24TPA1288860"],"award-info":[{"award-number":["24TPA1288860"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"award":["24TPA1288860"],"award-info":[{"award-number":["24TPA1288860"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011781","name":"Shriners Hospitals for Children","doi-asserted-by":"publisher","award":["87300-NCA-24"],"award-info":[{"award-number":["87300-NCA-24"]}],"id":[{"id":"10.13039\/100011781","id-type":"DOI","asserted-by":"publisher"}]},{"award":["87300-NCA-24"],"award-info":[{"award-number":["87300-NCA-24"]}],"id":[{"id":"https:\/\/ror.org\/03e8tm275","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Bone regeneration remains a significant clinical challenge, particularly for large or critical-sized defects caused by trauma, disease, or congenital abnormalities. Mesenchymal stem cells (MSCs) have emerged as a promising cell source for bone tissue engineering, with their osteogenic differentiation playing a crucial role in bone repair. Biomaterials serve as scaffolds that facilitate MSC-mediated bone regeneration by providing structural support and mimicking the extracellular matrix (ECM). This review explores recent advancements in biomaterials designed to promote MSC osteogenesis through two primary approaches: biochemical and physicomechanical stimuli. Therapeutic agent-loaded scaffolds, incorporating growth factors, small molecules, gene materials, peptides, proteins, and extracellular vesicles (EVs), have been extensively studied for their ability to enhance osteogenic differentiation. However, concerns regarding toxicity, off-target effects, and regulatory limitations have led to increasing interest in biomaterials that utilize physicomechanical cues such as stiffness, viscoelasticity, topography, porosity, and dynamic forces (shear stress, compression, vibration) as alternative or complementary strategies. Furthermore, the synergistic effects of multiple physicomechanical cues are being explored to regulate MSC behavior for promoting bone regeneration. This review discusses current challenges, emerging trends, and future directions in the development of next-generation biomaterials that integrate biochemical and physicomechanical approaches for clinical applications in bone repair and regeneration.<\/jats:p>","DOI":"10.3390\/ijms27156753","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T13:07:33Z","timestamp":1785244053000},"page":"6753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Biochemical and Physicomechanical Cues of Biomaterials Guide Osteogenic Differentiation of Mesenchymal Stem Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2729-8401","authenticated-orcid":false,"given":"Bofeng","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Surgery, University of California Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Maalal","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8533-7344","authenticated-orcid":false,"given":"Dake","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California Davis, Sacramento, CA 95817, USA"},{"name":"Shriners Children\u2019s Northern California, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","first-page":"e17705","article-title":"Bone Grafts in Trauma and Orthopaedics","volume":"13","author":"Archunan","year":"2021","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1007\/s43465-024-01249-6","article-title":"Nonunion of Fractures: A Review of Epidemiology, Diagnosis, and Clinical Features in Recent Literature","volume":"58","author":"Gharu","year":"2024","journal-title":"Indian J. Orthop."},{"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":"767","DOI":"10.1007\/s12603-023-1971-4","article-title":"Sex Specific Global Burden of Osteoporosis in 204 Countries and Territories, from 1990 to 2030: An Age-Period-Cohort Modeling Study","volume":"27","author":"Zhu","year":"2023","journal-title":"J. Nutr. Health Aging"},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1046\/j.1440-1622.2001.02128.x","article-title":"Synthetic bone graft substitutes","volume":"71","author":"Moore","year":"2001","journal-title":"ANZ J. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1007\/s12018-015-9194-9","article-title":"Evolution of Bone Grafting: Bone Grafts and Tissue Engineering Strategies for Vascularized Bone Regeneration","volume":"13","author":"Griffin","year":"2015","journal-title":"Clin. Rev. Bone Miner. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"112466","DOI":"10.1016\/j.msec.2021.112466","article-title":"FDA-approved bone grafts and bone graft substitute devices in bone regeneration","volume":"130","author":"Gillman","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S561","DOI":"10.3928\/0147-7447-20020502-04","article-title":"Limitations of Autograft and Allograft: New Synthetic Solutions","volume":"25","author":"Betz","year":"2002","journal-title":"Orthopedics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1302\/0301-620X.89B5.19039","article-title":"Bone allografts: What they can offer and what they cannot","volume":"89-B","author":"Delloye","year":"2007","journal-title":"J. Bone Jt. Surg. Br. Vol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"496","DOI":"10.4103\/0970-9290.87084","article-title":"Bone allografts: A review of safety and efficacy","volume":"22","author":"Grover","year":"2011","journal-title":"Indian J. Dent. Res."},{"key":"ref_13","first-page":"65","article-title":"Manufacturing artificial bone allografts: A perspective","volume":"3","author":"Steijvers","year":"2022","journal-title":"Biomater. Transl."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Busch, A., J\u00e4ger, M., Mayer, C., and Sowislok, A. (2021). Functionalization of Synthetic Bone Substitutes. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094412"},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.biomaterials.2013.10.054","article-title":"Controlling stem cell-mediated bone regeneration through tailored mechanical properties of collagen scaffolds","volume":"35","author":"Sun","year":"2014","journal-title":"Biomaterials"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Hao, D., Swindell, H.S., Ramasubramanian, L., Liu, R., Lam, K.S., Farmer, D.L., and Wang, A. (2020). Extracellular Matrix Mimicking Nanofibrous Scaffolds Modified With Mesenchymal Stem Cell-Derived Extracellular Vesicles for Improved Vascularization. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00633"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lin, X., Patil, S., Gao, Y.-G., and Qian, A. (2020). The Bone Extracellular Matrix in Bone Formation and Regeneration. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00757"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1089\/ten.tea.2017.0026","article-title":"Extracellular Matrices for Bone Regeneration: A Literature Review","volume":"23","author":"Mansour","year":"2017","journal-title":"Tissue Eng. Part A"},{"key":"ref_20","first-page":"179","article-title":"A bioactive material with dual integrin-targeting ligands regulates specific endogenous cell adhesion and promotes vascularized bone regeneration in adult and fetal bone defects","volume":"20","author":"Hao","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kazimierczak, P., and Przekora, A. (2022). Bioengineered Living Bone Grafts\u2014A Concise Review on Bioreactors and Production Techniques In Vitro. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031765"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Liu, M., and Lv, Y. (2018). Reconstructing Bone with Natural Bone Graft: A Review of In Vivo Studies in Bone Defect Animal Model. Nanomaterials, 8.","DOI":"10.3390\/nano8120999"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6021","DOI":"10.7150\/thno.70448","article-title":"Engineered extracellular vesicles with high collagen-binding affinity present superior in situ retention and therapeutic efficacy in tissue repair","volume":"12","author":"Hao","year":"2022","journal-title":"Theranostics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/s41578-020-0204-2","article-title":"Materials design for bone-tissue engineering","volume":"5","author":"Koons","year":"2020","journal-title":"Nat. Rev. Mater."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1089\/hum.2010.173","article-title":"The Regulation of Differentiation in Mesenchymal Stem Cells","volume":"21","author":"Augello","year":"2010","journal-title":"Hum. Gene Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/s41580-021-00386-2","article-title":"Translational control of stem cell function","volume":"22","author":"Saba","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.ijbiomac.2021.02.052","article-title":"Osteogenic potential of the growth factors and bioactive molecules in bone regeneration","volume":"175","author":"Safari","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.msec.2017.04.038","article-title":"Bone regeneration: Biomaterials as local delivery systems with improved osteoinductive properties","volume":"82","author":"Martin","year":"2018","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1002\/jcb.29462","article-title":"Experimental study of the synergistic effect and network regulation mechanisms of an applied combination of BMP-2, VEGF, and TGF-\u03b21 on osteogenic differentiation","volume":"121","author":"Wang","year":"2020","journal-title":"J. Cell. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.22203\/eCM.v027a01","article-title":"VEGF and BMP-2 promote bone regeneration by facilitating bone marrow stem cell homing and differentiation","volume":"27","author":"Zhang","year":"2014","journal-title":"Eur. Cells Mater."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1002\/jcp.22698","article-title":"An update on transforming growth factor-\u03b2 (TGF-\u03b2): Sources, types, functions and clinical applicability for cartilage\/bone healing","volume":"226","author":"Patil","year":"2011","journal-title":"J. Cell. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"31612","DOI":"10.18632\/oncotarget.15779","article-title":"A novel bioactive osteogenesis scaffold delivers ascorbic acid, \u03b2-glycerophosphate, and dexamethasone in vivo to promote bone regeneration","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"126","DOI":"10.14310\/horm.2002.1339","article-title":"Statins, bone formation and osteoporosis: Hope or hype?","volume":"11","author":"Tsartsalis","year":"2012","journal-title":"Hormones"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4447","DOI":"10.1039\/D1MA00092F","article-title":"Engineering bioactive synthetic polymers for biomedical applications: A review with emphasis on tissue engineering and controlled release","volume":"2","author":"Alvarez","year":"2021","journal-title":"Mater. Adv."},{"key":"ref_35","first-page":"401","article-title":"Bioactive hydrogels for bone regeneration","volume":"3","author":"Bai","year":"2018","journal-title":"Bioact. Mater."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"120785","DOI":"10.1016\/j.biomaterials.2021.120785","article-title":"Programmed BMP-2 release from biphasic calcium phosphates for optimal bone regeneration","volume":"272","author":"Han","year":"2021","journal-title":"Biomaterials"},{"key":"ref_37","first-page":"26","article-title":"Exosome-functionalized magnesium-organic framework-based scaffolds with osteogenic, angiogenic and anti-inflammatory properties for accelerated bone regeneration","volume":"18","author":"Kang","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1002\/jbm.b.34967","article-title":"Three-dimensional cell-laden collagen scaffolds: From biochemistry to bone bioengineering","volume":"110","author":"Nogueira","year":"2022","journal-title":"J. Biomed. Mater. Res. Part B Appl. Biomater."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hsieh, M.-K., Wu, C.-J., Su, X.-C., Chen, Y.-C., Tsai, T.-T., Niu, C.-C., Lai, P.-L., and Wu, S.-C. (2019). Bone regeneration in Ds-Red pig calvarial defect using allogenic transplantation of EGFP-pMSCs\u2014A comparison of host cells and seeding cells in the scaffold. PLoS ONE, 14.","DOI":"10.1101\/599670"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.7150\/thno.84759","article-title":"Integrating physicomechanical and biological strategies for BTE: Biomaterials-induced osteogenic differentiation of MSCs","volume":"13","author":"Shi","year":"2023","journal-title":"Theranostics"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Sun, Y., Wan, B., Wang, R., Zhang, B., Luo, P., Wang, D., Nie, J.-J., Chen, D., and Wu, X. (2022). Mechanical Stimulation on Mesenchymal Stem Cells and Surrounding Microenvironments in Bone Regeneration: Regulations and Applications. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.808303"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Josephson, T.O., and Morgan, E.F. (2023). Harnessing mechanical cues in the cellular microenvironment for bone regeneration. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1232698"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2000365","DOI":"10.1002\/mabi.202000365","article-title":"Biomaterial Properties Modulating Bone Regeneration","volume":"21","author":"Zhu","year":"2021","journal-title":"Macromol. Biosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"155206","DOI":"10.1016\/j.cej.2024.155206","article-title":"Hydrogels mimicking the viscoelasticity of extracellular matrix for regenerative medicine: Design, application, and molecular mechanism","volume":"498","author":"Li","year":"2024","journal-title":"Chem. Eng. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1067\/mpr.2000.111966","article-title":"A role for surface topography in creating and maintaining bone at titanium endosseous implants","volume":"84","author":"Cooper","year":"2000","journal-title":"J. Prosthet. Dent."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4978","DOI":"10.1039\/D2BM00485B","article-title":"Interplay of matrix stiffness and stress relaxation in directing osteogenic differentiation of mesenchymal stem cells","volume":"10","author":"Feuillie","year":"2022","journal-title":"Biomater. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.jmbbm.2013.01.012","article-title":"Controlling dynamic mechanical properties and degradation of composites for bone regeneration by means of filler content","volume":"20","author":"Barbieri","year":"2013","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Hao, D., Lopez, J.-M., Chen, J., Iavorovschi, A.M., Lelivelt, N.M., and Wang, A. (2022). Engineering Extracellular Microenvironment for Tissue Regeneration. Bioengineering, 9.","DOI":"10.3390\/bioengineering9050202"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"103282","DOI":"10.1016\/j.mtbio.2026.103282","article-title":"From bone replacement to regeneration. A biomaterials started journey","volume":"38","author":"Planell","year":"2026","journal-title":"Mater. Today Bio"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"121431","DOI":"10.1016\/j.biomaterials.2022.121431","article-title":"Biomaterial-induced pathway modulation for bone regeneration","volume":"283","author":"Vermeulen","year":"2022","journal-title":"Biomaterials"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Re, F., Gabusi, E., Manferdini, C., Russo, D., and Lisignoli, G. (2021). Bone Regeneration Improves with Mesenchymal Stem Cell Derived Extracellular Vesicles (EVs) Combined with Scaffolds: A Systematic Review. Biology, 10.","DOI":"10.3390\/biology10070579"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2100463","DOI":"10.1002\/adem.202100463","article-title":"How Does Scaffold Porosity Conduct Bone Tissue Regeneration?","volume":"23","author":"Mohammadi","year":"2021","journal-title":"Adv. Eng. Mater."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Tang, G., Liu, Z., Liu, Y., Yu, J., Wang, X., Tan, Z., and Ye, X. (2021). Recent Trends in the Development of Bone Regenerative Biomaterials. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.665813"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Abdelaziz, A.G., Nageh, H., Abdo, S.M., Abdalla, M.S., Amer, A.A., Abdal-hay, A., and Barhoum, A. (2023). A Review of 3D Polymeric Scaffolds for Bone Tissue Engineering: Principles, Fabrication Techniques, Immunomodulatory Roles, and Challenges. Bioengineering, 10.","DOI":"10.3390\/bioengineering10020204"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Venkataiah, V.S., Yahata, Y., Kitagawa, A., Inagaki, M., Kakiuchi, Y., Nakano, M., Suzuki, S., Handa, K., and Saito, M. (2021). Clinical Applications of Cell-Scaffold Constructs for Bone Regeneration Therapy. Cells, 10.","DOI":"10.3390\/cells10102687"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.addr.2007.03.016","article-title":"Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering","volume":"59","author":"Lee","year":"2007","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.addr.2018.06.002","article-title":"Engineered delivery strategies for enhanced control of growth factor activities in wound healing","volume":"146","author":"Niu","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"\u0141uczak, J.W., Palusi\u0144ska, M., Matak, D., Pietrzak, D., Nakielski, P., Lewicki, S., Grodzik, M., and Szyma\u0144ski, \u0141. (2024). The Future of Bone Repair: Emerging Technologies and Biomaterials in Bone Regeneration. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252312766"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"De Pace, R., Molinari, S., Mazzoni, E., and Perale, G. (2025). Bone Regeneration: A Review of Current Treatment Strategies. J. Clin. Med., 14.","DOI":"10.3390\/jcm14061838"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"102","DOI":"10.4252\/wjsc.v16.i2.102","article-title":"Crosstalk between Wnt and bone morphogenetic protein signaling during osteogenic differentiation","volume":"16","author":"Arya","year":"2024","journal-title":"World J. Stem Cells"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Yan, C.-P., Wang, X.-K., Jiang, K., Yin, C., Xiang, C., Wang, Y., Pu, C., Chen, L., and Li, Y.-L. (2022). \u03b2-Ecdysterone Enhanced Bone Regeneration Through the BMP-2\/SMAD\/RUNX2\/Osterix Signaling Pathway. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.883228"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Kowalczewski, C.J., and Saul, J.M. (2018). Biomaterials for the Delivery of Growth Factors and Other Therapeutic Agents in Tissue Engineering Approaches to Bone Regeneration. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00513"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.msec.2016.02.080","article-title":"Bone regeneration using injectable BMP-7 loaded chitosan microparticles in rat femoral defect","volume":"63","author":"Mantripragada","year":"2016","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1007\/s10856-010-4150-1","article-title":"Effect of scaffold architecture and BMP-2\/BMP-7 delivery on in vitro bone regeneration","volume":"21","author":"Yilgor","year":"2010","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.actbio.2019.10.033","article-title":"Silicon substituted hydroxyapatite\/VEGF scaffolds stimulate bone regeneration in osteoporotic sheep","volume":"101","author":"Casarrubios","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.actbio.2024.10.044","article-title":"Nanofibrous 3D scaffolds capable of individually controlled BMP and FGF release for the regulation of bone regeneration","volume":"190","author":"Rambhia","year":"2024","journal-title":"Acta Biomater."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"111913","DOI":"10.1016\/j.matdes.2023.111913","article-title":"Strategy to improve endogenous bone regeneration of 3D-printed PCL\/nano-HA composite scaffold: Collagen designs with BMP-2 and FGF-2","volume":"229","author":"Cho","year":"2023","journal-title":"Mater. Des."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6698","DOI":"10.1016\/j.biomaterials.2012.06.021","article-title":"Delivery of PDGF-B and BMP-7 by mesoporous bioglass\/silk fibrin scaffolds for the repair of osteoporotic defects","volume":"33","author":"Zhang","year":"2012","journal-title":"Biomaterials"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.actbio.2017.12.004","article-title":"Preparation of dexamethasone-loaded biphasic calcium phosphate nanoparticles\/collagen porous composite scaffolds for bone tissue engineering","volume":"67","author":"Chen","year":"2018","journal-title":"Acta Biomater."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"153662","DOI":"10.1016\/j.cej.2024.153662","article-title":"3D printed biomimetic composite scaffolds with sequential releasing of copper ions and dexamethasone for cascade regulation of angiogenesis and osteogenesis","volume":"496","author":"Song","year":"2024","journal-title":"Chem. Eng. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"212838","DOI":"10.1016\/j.bioadv.2022.212838","article-title":"Controlling sustained statins release in multi-layered composite scaffolds for healing of osteoporotic bone defects","volume":"137","author":"Liu","year":"2022","journal-title":"Biomater. Adv."},{"key":"ref_72","first-page":"3074","article-title":"Lithium chloride promotes osteogenesis and suppresses apoptosis during orthodontic tooth movement in osteoporotic model via regulating autophagy","volume":"6","author":"Huang","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"45204","DOI":"10.1038\/srep45204","article-title":"Acceleration of bone regeneration by activating Wnt\/\u03b2-catenin signalling pathway via lithium released from lithium chloride\/calcium phosphate cement in osteoporosis","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biomaterials.2017.10.025","article-title":"Porous composite scaffold incorporating osteogenic phytomolecule icariin for promoting skeletal regeneration in challenging osteonecrotic bone in rabbits","volume":"153","author":"Lai","year":"2018","journal-title":"Biomaterials"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"102886","DOI":"10.1016\/j.mtbio.2026.102886","article-title":"Biomaterial-assisted gene therapy for bone repair","volume":"37","author":"Yang","year":"2026","journal-title":"Mater. Today Bio"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Bukharova, T.B., Nedorubova, I.A., Mokrousova, V.O., Meglei, A.Y., Basina, V.P., Nedorubov, A.A., Vasilyev, A.V., Grigoriev, T.E., Zagoskin, Y.D., and Chvalun, S.N. (2023). Adenovirus-Based Gene Therapy for Bone Regeneration: A Comparative Analysis of In Vivo and Ex Vivo BMP2 Gene Delivery. Cells, 12.","DOI":"10.3390\/cells12131762"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.bone.2012.06.029","article-title":"Synthesis and inflammatory response of a novel silk fibroin scaffold containing BMP7 adenovirus for bone regeneration","volume":"51","author":"Zhang","year":"2012","journal-title":"Bone"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Lackington, W.A., Gomez-Sierra, M.A., Gonz\u00e1lez-V\u00e1zquez, A., O\u2019Brien, F.J., Stoddart, M.J., and Thompson, K. (2020). Non-viral Gene Delivery of Interleukin-1 Receptor Antagonist Using Collagen-Hydroxyapatite Scaffold Protects Rat BM-MSCs From IL-1\u03b2-Mediated Inhibition of Osteogenesis. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.582012"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"6348","DOI":"10.1007\/s12274-022-4292-8","article-title":"A novel gene-activated matrix composed of PEI\/plasmid-BMP2 complexes and hydroxyapatite\/chitosan-microspheres promotes bone regeneration","volume":"15","author":"Ding","year":"2022","journal-title":"Nano Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1089\/ten.tea.2018.0112","article-title":"An Improved, Chemically Modified RNA Encoding BMP-2 Enhances Osteogenesis In Vitro and In Vivo","volume":"25","author":"Zhang","year":"2019","journal-title":"Tissue Eng. Part A"},{"key":"ref_81","first-page":"1","article-title":"MicroRNA-activated hydrogel scaffold generated by 3D printing accelerates bone regeneration","volume":"10","author":"Pan","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1039\/C9TB02309G","article-title":"Surface modification of polymeric electrospun scaffolds via a potent and high-affinity integrin \u03b14\u03b21 ligand improved the adhesion, spreading and survival of human chorionic villus-derived mesenchymal stem cells: A new insight for fetal tissue engineering","volume":"8","author":"Hao","year":"2020","journal-title":"J. Mater. Chem. B"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1021\/acschembio.7b00118","article-title":"Discovery and Characterization of a Potent and Specific Peptide Ligand Targeting Endothelial Progenitor Cells and Endothelial Cells for Tissue Regeneration","volume":"12","author":"Hao","year":"2017","journal-title":"ACS Chem. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.actbio.2020.03.005","article-title":"Rapid endothelialization of small diameter vascular grafts by a bioactive integrin-binding ligand specifically targeting endothelial progenitor cells and endothelial cells","volume":"108","author":"Hao","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s44258-024-00037-z","article-title":"In-situ engineering of native extracellular matrix to improve vascularization and tissue regeneration at the ischemic injury site","volume":"2","author":"Hao","year":"2024","journal-title":"Med-X"},{"key":"ref_86","first-page":"467","article-title":"A bio-instructive parylene-based conformal coating suppresses thrombosis and intimal hyperplasia of implantable vascular devices","volume":"28","author":"Hao","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Hao, D., Liu, R., Gao, K., He, C., He, S., Zhao, C., Sun, G., Farmer, D.L., Panitch, A., and Lam, K.S. (2020). Developing an Injectable Nanofibrous Extracellular Matrix Hydrogel With an Integrin \u03b1v\u03b23 Ligand to Improve Endothelial Cell Survival, Engraftment and Vascularization. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00890"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13287-019-1138-8","article-title":"Potential long-term treatment of hemophilia A by neonatal co-transplantation of cord blood-derived endothelial colony-forming cells and placental mesenchymal stromal cells","volume":"10","author":"Gao","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"5089","DOI":"10.1016\/j.biomaterials.2006.05.050","article-title":"Ectopic bone formation in collagen sponge self-assembled peptide\u2013amphiphile nanofibers hybrid scaffold in a perfusion culture bioreactor","volume":"27","author":"Hosseinkhani","year":"2006","journal-title":"Biomaterials"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Goldbloom-Helzner, L., Hao, D., and Wang, A. (2019). Developing Regenerative Treatments for Developmental Defects, Injuries, and Diseases Using Extracellular Matrix Collagen-Targeting Peptides. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174072"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"130147","DOI":"10.1016\/j.cej.2021.130147","article-title":"Copper peptide-incorporated 3D-printed silk-based scaffolds promote vascularized bone regeneration","volume":"422","author":"Zhou","year":"2021","journal-title":"Chem. Eng. J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1021\/acsbiomaterials.4c02198","article-title":"Recent Advances in Peptide-Functionalized Hydrogels for Bone Tissue Engineering","volume":"11","author":"Li","year":"2025","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1111\/jcmm.12045","article-title":"Mechanotransduction at focal adhesions: From physiology to cancer development","volume":"17","author":"Seong","year":"2013","journal-title":"J. Cell. Mol. Med."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Kumar, V.B., Tiwari, O.S., Finkelstein-Zuta, G., Rencus-Lazar, S., and Gazit, E. (2023). Design of Functional RGD Peptide-Based Biomaterials for Tissue Engineering. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020345"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1093\/rb\/rbx011","article-title":"The use of bioactive peptides to modify materials for bone tissue repair","volume":"4","author":"Wang","year":"2017","journal-title":"Regen. Biomater."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"9917","DOI":"10.1016\/j.biomaterials.2013.09.002","article-title":"Umbilical cord and bone marrow mesenchymal stem cell seeding on macroporous calcium phosphate for bone regeneration in rat cranial defects","volume":"34","author":"Chen","year":"2013","journal-title":"Biomaterials"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2203131","DOI":"10.1002\/adhm.202203131","article-title":"Sustained Release of BMSC-EVs from 3D Printing Gel\/HA\/nHAP Scaffolds for Promoting Bone Regeneration in Diabetic Rats","volume":"12","author":"Yang","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"45622","DOI":"10.1038\/srep45622","article-title":"Extracellular Vesicle-functionalized Decalcified Bone Matrix Scaffolds with Enhanced Pro-angiogenic and Pro-bone Regeneration Activities","volume":"7","author":"Xie","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_99","first-page":"175","article-title":"Bioengineered extracellular vesicle-loaded bioscaffolds for therapeutic applications in regenerative medicine","volume":"2","author":"Lazar","year":"2021","journal-title":"Extracell. Vesicles Circ. Nucl. Acids"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"174942","DOI":"10.1155\/2012\/174942","article-title":"Scaffolds for Growth Factor Delivery as Applied to Bone Tissue Engineering","volume":"2012","author":"Blackwood","year":"2012","journal-title":"Int. J. Polym. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1016\/j.injury.2005.07.034","article-title":"Clinical applications of BMPs","volume":"36","author":"Biase","year":"2005","journal-title":"Injury"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/ten.teb.2015.0357","article-title":"A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2","volume":"22","author":"James","year":"2016","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"dmm033084","DOI":"10.1242\/dmm.033084","article-title":"Animal models for bone tissue engineering and modelling disease","volume":"11","author":"McGovern","year":"2018","journal-title":"Dis. Models Mech."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1089\/ten.teb.2009.0658","article-title":"The Design and Use of Animal Models for Translational Research in Bone Tissue Engineering and Regenerative Medicine","volume":"16","author":"Muschler","year":"2010","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1186\/s13018-026-06697-4","article-title":"Animal models for critical-sized long-bone defects and long-bone non-union: A scoping review","volume":"21","author":"Maai","year":"2026","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"18124","DOI":"10.1039\/C9RA02765C","article-title":"Mimicking growth factors: Role of small molecule scaffold additives in promoting tissue regeneration and repair","volume":"9","author":"Goonoo","year":"2019","journal-title":"RSC Adv."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Park, S.-Y., Kim, K.-H., Kim, S., Lee, Y.-M., and Seol, Y.-J. (2019). BMP-2 Gene Delivery-Based Bone Regeneration in Dentistry. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11080393"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Ross, A., Sauce-Guevara, M.A., Alarcon, E.I., and Mendez-Rojas, M.A. (2022). Peptide Biomaterials for Tissue Regeneration. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.893936"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"101978","DOI":"10.1016\/j.scr.2020.101978","article-title":"Strategies for scalable manufacturing and translation of MSC-derived extracellular vesicles","volume":"48","author":"Adlerz","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1515\/mr-2024-0023","article-title":"Biophysical stimuli for promoting bone repair and regeneration","volume":"5","author":"Bai","year":"2025","journal-title":"Med. Rev."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"139883","DOI":"10.1016\/j.ijbiomac.2025.139883","article-title":"Antibacterial and osteogenic properties of chitosan-polyethylene glycol nanofibre-coated 3D printed scaffold with vancomycin and insulin-like growth factor-1 release for bone repair","volume":"298","author":"Salehi","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_112","first-page":"56623","article-title":"Sustained Release of Dexamethasone from 3D-Printed Scaffolds Modulates Macrophage Activation and Enhances Osteogenic Differentiation","volume":"15","author":"Majrashi","year":"2023","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e375","DOI":"10.1097\/BPO.0000000000000859","article-title":"Complication Rates After Bone Morphogenetic Protein (BMP) Use in Orthopaedic Surgery in Children: A Concise Multicenter Retrospective Cohort Study","volume":"37","author":"Garg","year":"2017","journal-title":"J. Pediatr. Orthop."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"635","DOI":"10.3171\/2014.8.PEDS13665","article-title":"Bone morphogenetic protein\u2013associated complications in pediatric spinal fusion in the early postoperative period: An analysis of 4658 patients and review of the literature: Clinical article","volume":"14","author":"Rocque","year":"2014","journal-title":"J. Neurosurg. Pediatr."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"324","DOI":"10.7150\/ijbs.10567","article-title":"Optimization of pre-transplantation conditions to enhance the efficacy of mesenchymal stem cells","volume":"11","author":"Haque","year":"2015","journal-title":"Int. J. Biol. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"748","DOI":"10.4252\/wjsc.v11.i10.748","article-title":"Enhancing survival, engraftment, and osteogenic potential of mesenchymal stem cells","volume":"11","year":"2019","journal-title":"World J. Stem Cells"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s41467-019-14000-9","article-title":"Integrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities","volume":"11","author":"Clark","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/mabi.200900107","article-title":"Vascularization in Bone Tissue Engineering: Physiology, Current Strategies, Major Hurdles and Future Challenges","volume":"10","author":"Santos","year":"2010","journal-title":"Macromol. Biosci."},{"key":"ref_119","first-page":"492","article-title":"The PCK2-glycolysis axis assists three-dimensional-stiffness maintaining stem cell osteogenesis","volume":"18","author":"Li","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"tkaa029","DOI":"10.1093\/burnst\/tkaa029","article-title":"Stiffness-mediated mesenchymal stem cell fate decision in 3D-bioprinted hydrogels","volume":"8","author":"Liu","year":"2020","journal-title":"Burns Trauma"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"111223","DOI":"10.1016\/j.compositesb.2024.111223","article-title":"Bioinspired semi-flexible hydrogel with anti-inflammatory potential for natural tissue-mimicking bone regeneration","volume":"273","author":"Lee","year":"2024","journal-title":"Compos. Part B Eng."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1039\/D1MH00244A","article-title":"Microscopic local stiffening in a supramolecular hydrogel network expedites stem cell mechanosensing in 3D and bone regeneration","volume":"8","author":"Yuan","year":"2021","journal-title":"Mater. Horiz."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.actbio.2016.06.034","article-title":"A newly identified mechanism involved in regulation of human mesenchymal stem cells by fibrous substrate stiffness","volume":"42","author":"Yuan","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1901407","DOI":"10.1002\/adfm.201901407","article-title":"3D Superelastic Scaffolds Constructed from Flexible Inorganic Nanofibers with Self-Fitting Capability and Tailorable Gradient for Bone Regeneration","volume":"29","author":"Wang","year":"2019","journal-title":"Adv. Funct. Mater."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/wrr.13154","article-title":"Development of pro-angiogenic skin substitutes for wound healing","volume":"32","author":"Song","year":"2024","journal-title":"Wound Repair Regen."},{"key":"ref_126","first-page":"167","article-title":"A bioactive compliant vascular graft modulates macrophage polarization and maintains patency with robust vascular remodeling","volume":"19","author":"Stahl","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/nmat4489","article-title":"Hydrogels with tunable stress relaxation regulate stem cell fate and activity","volume":"15","author":"Chaudhuri","year":"2016","journal-title":"Nat. Mater."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"120607","DOI":"10.1016\/j.biomaterials.2020.120607","article-title":"Hydrogel mechanics are a key driver of bone formation by mesenchymal stromal cell spheroids","volume":"269","author":"Whitehead","year":"2021","journal-title":"Biomaterials"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"21020","DOI":"10.1021\/acsnano.2c08699","article-title":"Bone ECM-like 3D Printing Scaffold with Liquid Crystalline and Viscoelastic Microenvironment for Bone Regeneration","volume":"16","author":"Liu","year":"2022","journal-title":"ACS Nano"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1126\/science.abh3602","article-title":"Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury","volume":"374","author":"Sasselli","year":"2021","journal-title":"Science"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1126\/science.34.870.279","article-title":"On the Stereotropism of Embryonic Cells","volume":"34","author":"Harrison","year":"1911","journal-title":"Science"},{"key":"ref_132","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_133","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.biomaterials.2015.05.030","article-title":"Surface topography enhances differentiation of mesenchymal stem cells towards osteogenic and adipogenic lineages","volume":"61","author":"Abagnale","year":"2015","journal-title":"Biomaterials"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"8858","DOI":"10.1021\/acsami.8b21393","article-title":"Controlled Nanoscale Topographies for Osteogenic Differentiation of Mesenchymal Stem Cells","volume":"11","author":"Pedrosa","year":"2019","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.actbio.2018.04.030","article-title":"The role of the micro-pattern and nano-topography of hydroxyapatite bioceramics on stimulating osteogenic differentiation of mesenchymal stem cells","volume":"73","author":"Zhao","year":"2018","journal-title":"Acta Biomater."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"eabg3089","DOI":"10.1126\/sciadv.abg3089","article-title":"Biomaterials with structural hierarchy and controlled 3D nanotopography guide endogenous bone regeneration","volume":"7","author":"Chen","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_137","first-page":"460","article-title":"Bioactive extracellular matrix scaffolds engineered with proangiogenic proteoglycan mimetics and loaded with endothelial progenitor cells promote neovascularization and diabetic wound healing","volume":"10","author":"He","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Song, H., Gao, K., Hao, D., Li, A., Liu, R., Anggito, B., Yin, B., Jin, Q., Dartora, V., and Lam, K.S. (2023). Engineered multi-functional, pro-angiogenic collagen-based scaffolds loaded with endothelial cells promote large deep burn wound healing. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1125209"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"19468","DOI":"10.1038\/srep19468","article-title":"Design and Fabrication of 3D printed Scaffolds with a Mechanical Strength Comparable to Cortical Bone to Repair Large Bone Defects","volume":"6","author":"Newman","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1700401","DOI":"10.1002\/advs.201700401","article-title":"3D Printing of Lotus Root-Like Biomimetic Materials for Cell Delivery and Tissue Regeneration","volume":"4","author":"Feng","year":"2017","journal-title":"Adv. Sci."},{"key":"ref_141","first-page":"278","article-title":"3D bioactive composite scaffolds for bone tissue engineering","volume":"3","author":"Turnbull","year":"2018","journal-title":"Bioact. Mater."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"He, S., Zhu, J., Jing, Y., Long, S., Tang, L., Cheng, L., and Shi, Z. (2024). Effect of 3D-Printed Porous Titanium Alloy Pore Structure on Bone Regeneration: A Review. Coatings, 14.","DOI":"10.3390\/coatings14030253"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Yong, K.W., Choi, J.R., Choi, J.Y., and Cowie, A.C. (2020). Recent Advances in Mechanically Loaded Human Mesenchymal Stem Cells for Bone Tissue Engineering. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165816"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.snb.2015.05.073","article-title":"Effect of mechanical stress on differentiation of mouse mesenchymal stem cells seeded into an octacalcium phosphate\u2013gelatin scaffold","volume":"220","author":"Yamada","year":"2015","journal-title":"Sens. Actuators B Chem."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"143","DOI":"10.4248\/IJOS.09021","article-title":"Expression of Bone-related Genes in Bone Marrow MSCs after Cyclic Mechanical Strain: Implications for Distraction Osteogenesis","volume":"1","author":"Qi","year":"2009","journal-title":"Int. J. Oral Sci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"20417314211019375","DOI":"10.1177\/20417314211019375","article-title":"Induction of osteogenic differentiation of bone marrow stromal cells on 3D polyester-based scaffolds solely by subphysiological fluidic stimulation in a laminar flow bioreactor","volume":"12","author":"Yamada","year":"2021","journal-title":"J. Tissue Eng."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"12944","DOI":"10.1038\/s41598-019-49422-4","article-title":"Design, construction and characterisation of a novel nanovibrational bioreactor and cultureware for osteogenesis","volume":"9","author":"Campsie","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1002\/jbm.a.36267","article-title":"Hydrostatic pressure in combination with topographical cues affects the fate of bone marrow-derived human mesenchymal stem cells for bone tissue regeneration","volume":"106","author":"Reinwald","year":"2018","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"e2039","DOI":"10.1002\/term.2635","article-title":"Biomimetic fetal rotation bioreactor for engineering bone tissues\u2014Effect of cyclic strains on upregulation of osteogenic gene expression","volume":"12","author":"Ravichandran","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"rbae136","DOI":"10.1093\/rb\/rbae136","article-title":"Viscoelastic hydrogel combined with dynamic compression promotes osteogenic differentiation of bone marrow mesenchymal stem cells and bone repair in rats","volume":"12","author":"Yang","year":"2025","journal-title":"Regen. Biomater."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1002\/elsc.202200029","article-title":"Assessing the combined effect of surface topography and substrate rigidity in human bone marrow stem cell cultures","volume":"22","author":"Ribeiro","year":"2022","journal-title":"Eng. Life Sci."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1021\/acs.nanolett.9b04761","article-title":"Surface Roughness and Substrate Stiffness Synergize to Drive Cellular Mechanoresponse","volume":"20","author":"Hou","year":"2019","journal-title":"Nano Lett."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Wang, Z., Sun, Q., Li, Q., Li, S., and Li, X. (2023). Dynamic Hydrogels with Viscoelasticity and Tunable Stiffness for the Regulation of Cell Behavior and Fate. Materials, 16.","DOI":"10.3390\/ma16145161"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.apmt.2019.02.017","article-title":"The design and in vivo testing of a locally stiffness-matched porous scaffold","volume":"15","author":"Ghouse","year":"2019","journal-title":"Appl. Mater. Today"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.actbio.2015.10.048","article-title":"High-strength porous biomaterials for bone replacement: A strategy to assess the interplay between cell morphology, mechanical properties, bone ingrowth and manufacturing constraints","volume":"30","author":"Arabnejad","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.cell.2006.06.044","article-title":"Matrix Elasticity Directs Stem Cell Lineage Specification","volume":"126","author":"Engler","year":"2006","journal-title":"Cell"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2301081","DOI":"10.1002\/adhm.202301081","article-title":"Convergence of Calcium Channel Regulation and Mechanotransduction in Skeletal Regenerative Biomaterial Design","volume":"12","author":"LaGuardia","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_158","first-page":"323","article-title":"Cellular modulation by the mechanical cues from biomaterials for tissue engineering","volume":"2","author":"Wei","year":"2021","journal-title":"Biomater. Transl."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1111\/joa.12243","article-title":"Mechanical regulation of mesenchymal stem cell differentiation","volume":"227","author":"Steward","year":"2015","journal-title":"J. Anat."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"21258","DOI":"10.1073\/pnas.2006765117","article-title":"Nuclear mechanosensing controls MSC osteogenic potential through HDAC epigenetic remodeling","volume":"117","author":"Killaars","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"e49631","DOI":"10.7554\/eLife.49631","article-title":"Stimulation of Piezo1 by mechanical signals promotes bone anabolism","volume":"8","author":"Li","year":"2019","journal-title":"eLife"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Steinecker-Frohnwieser, B., Lohberger, B., Toegel, S., Windhager, R., Glanz, V., Kratschmann, C., Leithner, A., and Weigl, L. (2023). Activation of the Mechanosensitive Ion Channels Piezo1 and TRPV4 in Primary Human Healthy and Osteoarthritic Chondrocytes Exhibits Ion Channel Crosstalk and Modulates Gene Expression. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24097868"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2415185","DOI":"10.1002\/adfm.202415185","article-title":"Calcium-Capturing Hydrogel with Self-Reinforced Multi-Dynamic Networks for Effective Periodontal Bone Regeneration in Three-Dimension","volume":"35","author":"Zhang","year":"2025","journal-title":"Adv. Funct. Mater."},{"key":"ref_164","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_165","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.cytogfr.2005.01.009","article-title":"BMP receptor signaling: Transcriptional targets, regulation of signals, and signaling cross-talk","volume":"16","author":"Miyazono","year":"2005","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Raman, N., Imran, S.A.M., Ahmad Amin Noordin, K.B., Zaman, W.S.W.K., and Nordin, F. (2022). Mechanotransduction in Mesenchymal Stem Cells (MSCs) Differentiation: A Review. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094580"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/scrt318","article-title":"Mechanically induced osteogenic lineage commitment of stem cells","volume":"4","author":"Chen","year":"2013","journal-title":"Stem Cell Res. Ther."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"eadv8804","DOI":"10.1126\/sciadv.adv8804","article-title":"Architecture mechanics mediated osteogenic progression in bone regeneration of artificial scaffolds","volume":"11","author":"Long","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2300326","DOI":"10.1002\/adhm.202300326","article-title":"Dynamic Stiffening Hydrogel with Instructive Stiffening Timing Modulates Stem Cell Fate In Vitro and Enhances Bone Remodeling In Vivo","volume":"12","author":"Li","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.biocel.2015.10.011","article-title":"Overcoming translational challenges\u2014The delivery of mechanical stimuli in vivo","volume":"69","author":"Markides","year":"2015","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"e12046","DOI":"10.1002\/bmm2.12046","article-title":"Advanced strategies of scaffolds design for bone regeneration","volume":"1","author":"Song","year":"2023","journal-title":"BMEMat"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Nguyen, T.T., Wang, B., Alas, H., Jones, Q., Clark, C., Lazar, S., Malik, S., Graham, J., Talaat, Y., and Shin, C. (2025). Prosthesis Embodiment in Lower Extremity Limb Loss: A Narrative Review. Appl. Sci., 15.","DOI":"10.3390\/app15094952"},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Nicksic, P.J., Donnelly, D.A.T., Hesse, M., Bedi, S., Verma, N., Seitz, A.J., Shoffstall, A.J., Ludwig, K.A., Dingle, A.M., and Poore, S.O. (2022). Electronic Bone Growth Stimulators for Augmentation of Osteogenesis in In Vitro and In Vivo Models: A Narrative Review of Electrical Stimulation Mechanisms and Device Specifications. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.793945"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"2100073","DOI":"10.1002\/anbr.202100073","article-title":"(Bio)manufactured Solutions for Treatment of Bone Defects with an Emphasis on US-FDA Regulatory Science Perspective","volume":"2","author":"Ghelich","year":"2022","journal-title":"Adv. NanoBiomed Res."},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Riester, O., Borgolte, M., Csuk, R., and Deigner, H.-P. (2021). Challenges in Bone Tissue Regeneration: Stem Cell Therapy, Biofunctionality and Antimicrobial Properties of Novel Materials and Its Evolution. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010192"},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Han, D., Liu, W., Gong, J., Ma, Y., and Sun, Z. (2025). Challenges and future perspectives in using mesenchymal stem cells for efficient bone fracture healing. Front. Bioeng. Biotechnol., 13.","DOI":"10.3389\/fbioe.2025.1568914"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Gupta, D.K., Tiwari, A., Yadav, Y., Soni, P., and Joshi, M. (2024). Ensuring safety and efficacy in combination products: Regulatory challenges and best practices. Front. Med. Technol., 6.","DOI":"10.3389\/fmedt.2024.1377443"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/scrt158","article-title":"Mechanical control of tissue-engineered bone","volume":"4","author":"Hung","year":"2013","journal-title":"Stem Cell Res. Ther."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s10439-014-1104-7","article-title":"A Perspective on the Clinical Translation of Scaffolds for Tissue Engineering","volume":"43","author":"Webber","year":"2015","journal-title":"Ann. Biomed. Eng."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.biomaterials.2017.12.025","article-title":"Mesenchymal stem cell-macrophage crosstalk and bone healing","volume":"196","author":"Pajarinen","year":"2019","journal-title":"Biomaterials"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"4079","DOI":"10.2147\/JIR.S310831","article-title":"Nrf2 Regulates CHI3L1 to Suppress Inflammation and Improve Post-Traumatic Osteoarthritis","volume":"14","author":"Song","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41580-020-00279-w","article-title":"Mechanisms of bone development and repair","volume":"21","author":"Salhotra","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_183","first-page":"34","article-title":"Crosstalk between macrophages and mesenchymal stem cells shape patterns of osteogenesis and immunomodulation in mineralized collagen scaffolds","volume":"44","author":"Kolliopoulos","year":"2025","journal-title":"Bioact. Mater."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.it.2023.10.004","article-title":"Macrophage phenotypes and functions: Resolving inflammation and restoring homeostasis","volume":"44","author":"Franklin","year":"2023","journal-title":"Trends Immunol."},{"key":"ref_185","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_186","doi-asserted-by":"crossref","first-page":"9695239","DOI":"10.1155\/2019\/9695239","article-title":"Hypoxic Preconditioning Enhances Survival and Proangiogenic Capacity of Human First Trimester Chorionic Villus-Derived Mesenchymal Stem Cells for Fetal Tissue Engineering","volume":"2019","author":"Hao","year":"2019","journal-title":"Stem Cells Int."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"776","DOI":"10.4252\/wjsc.v13.i7.776","article-title":"Exosomal microRNAs from mesenchymal stem\/stromal cells: Biology and applications in neuroprotection","volume":"13","author":"Nasirishargh","year":"2021","journal-title":"World J. Stem Cells"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1522236","DOI":"10.1080\/20013078.2018.1522236","article-title":"Engineering mesenchymal stem cells to improve their exosome efficacy and yield for cell-free therapy","volume":"7","author":"Phan","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"2100924","DOI":"10.1002\/adfm.202100924","article-title":"Engineering Bioactive M2 Macrophage-Polarized Anti-Inflammatory, Antioxidant, and Antibacterial Scaffolds for Rapid Angiogenesis and Diabetic Wound Repair","volume":"31","author":"Tu","year":"2021","journal-title":"Adv. Funct. Mater."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"8835156","DOI":"10.1155\/2021\/8835156","article-title":"The Crosstalk between Mesenchymal Stem Cells and Macrophages in Bone Regeneration: A Systematic Review","volume":"2021","author":"Shin","year":"2021","journal-title":"Stem Cells Int."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/rb\/rbaa006","article-title":"Osteoimmunomodulatory effects of biomaterial modification strategies on macrophage polarization and bone regeneration","volume":"7","author":"Xie","year":"2020","journal-title":"Regen. Biomater."},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Kaur, H., and Ghorai, S.M. (2022). Role of Cytokines as Immunomodulators. Immunomodulators and Human Health, Springer Nature.","DOI":"10.1007\/978-981-16-6379-6_13"},{"key":"ref_193","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_194","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41413-025-00471-8","article-title":"Biomaterial-mediated macrophage polarization remodeling and sequential regulation: A potential strategy in bone infections treatment","volume":"13","author":"Shi","year":"2025","journal-title":"Bone Res."},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Yang, T., Fang, Z., Zhang, J., and Zheng, S. (2025). Physical cues in biomaterials modulate macrophage polarization for bone regeneration: A review. Front. Bioeng. Biotechnol., 13.","DOI":"10.3389\/fbioe.2025.1640560"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.actbio.2018.02.015","article-title":"Macrophage involvement affects matrix stiffness-related influences on cell osteogenesis under three-dimensional culture conditions","volume":"71","author":"He","year":"2018","journal-title":"Acta Biomater."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"2405097","DOI":"10.1002\/adhm.202405097","article-title":"Matrix Viscoelasticity Orchestrates Osteogenesis via Mechanotransduction Mediated Metabolic Switch in Macrophages","volume":"14","author":"Tao","year":"2025","journal-title":"Adv. Healthc. Mater."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"100466","DOI":"10.1016\/j.apmt.2019.100466","article-title":"Pore size-mediated macrophage M1-to-M2 transition influences new vessel formation within the compartment of a scaffold","volume":"18","author":"Yin","year":"2020","journal-title":"Appl. Mater. Today"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"2208639","DOI":"10.1002\/adfm.202208639","article-title":"Bone Repair Biomaterials: A Perspective from Immunomodulation","volume":"32","author":"Wang","year":"2022","journal-title":"Adv. Funct. Mater."},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"Halloran, D., Durbano, H.W., and Nohe, A. (2020). Bone Morphogenetic Protein-2 in Development and Bone Homeostasis. J. Dev. Biol., 8.","DOI":"10.3390\/jdb8030019"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.spinee.2011.04.023","article-title":"A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: Emerging safety concerns and lessons learned","volume":"11","author":"Carragee","year":"2011","journal-title":"Spine J."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1177\/154405910308201111","article-title":"Regulating Bone Formation via Controlled Scaffold Degradation","volume":"82","author":"Alsberg","year":"2003","journal-title":"J. Dent. Res."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"6162","DOI":"10.1016\/j.biomaterials.2010.04.028","article-title":"Relationships between degradability of silk scaffolds and osteogenesis","volume":"31","author":"Park","year":"2010","journal-title":"Biomaterials"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.actbio.2016.08.039","article-title":"Effect of the biodegradation rate controlled by pore structures in magnesium phosphate ceramic scaffolds on bone tissue regeneration in vivo","volume":"44","author":"Kim","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"7690","DOI":"10.1039\/C9TB02072A","article-title":"The long-term behaviors and differences in bone reconstruction of three polymer-based scaffolds with different degradability","volume":"7","author":"Huang","year":"2019","journal-title":"J. Mater. Chem. B"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.actbio.2020.07.028","article-title":"Fibrinogen and magnesium combination biomaterials modulate macrophage phenotype, NF-kB signaling and crosstalk with mesenchymal stem\/stromal cells","volume":"114","author":"Silva","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_207","first-page":"244","article-title":"Modulating macrophage activities to promote endogenous bone regeneration: Biological mechanisms and engineering approaches","volume":"6","author":"Niu","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Negut, I., and Bita, B. (2023). Exploring the Potential of Artificial Intelligence for Hydrogel Development\u2014A Short Review. Gels, 9.","DOI":"10.3390\/gels9110845"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"e70016","DOI":"10.1111\/srt.70016","article-title":"Recent advances in artificial intelligent strategies for tissue engineering and regenerative medicine","volume":"30","author":"Gharibshahian","year":"2024","journal-title":"Ski. Res. Technol."},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Goebel, S., Verna, V., Marty, C., and Neadle, S.W. (2023). General overview of global combination product regulatory landscape. The Combination Products Handbook, CRC Press.","DOI":"10.1201\/9781003300298-17"},{"key":"ref_211","first-page":"003","article-title":"Strategic approaches for selecting regulatory pathways in drug-device combination products: A comprehensive review","volume":"15","author":"Kumar","year":"2025","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1002\/jbm.a.34115","article-title":"Beta-tricalcium phosphate particles as a controlled release carrier of osteogenic proteins for bone tissue engineering","volume":"100A","author":"Hu","year":"2012","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1089\/ten.teb.2012.0727","article-title":"Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering\u2014Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery","volume":"19","author":"Santo","year":"2013","journal-title":"Tissue Eng. Part B Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6753\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:22:20Z","timestamp":1785385340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":213,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156753"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156753","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]}}}