{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:38:48Z","timestamp":1792795128944,"version":"4.5.0"},"reference-count":141,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:00:00Z","timestamp":1683072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\u2013NIA","award":["K99 R00 AG049958-01A1"],"award-info":[{"award-number":["K99 R00 AG049958-01A1"]}]},{"name":"NIH\u2013NIA","award":["202160339"],"award-info":[{"award-number":["202160339"]}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["K99 R00 AG049958-01A1"],"award-info":[{"award-number":["K99 R00 AG049958-01A1"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["202160339"],"award-info":[{"award-number":["202160339"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>Bone- and cartilage-related diseases, such as osteoporosis and osteoarthritis, affect millions of people worldwide, impairing their quality of life and increasing mortality. Osteoporosis significantly increases the bone fracture risk of the spine, hip, and wrist. For successful fracture treatment and to facilitate proper healing in the most complicated cases, one of the most promising methods is to deliver a therapeutic protein to accelerate bone regeneration. Similarly, in the setting of osteoarthritis, where degraded cartilage does not regenerate, therapeutic proteins hold great promise to promote new cartilage formation. For both osteoporosis and osteoarthritis treatments, targeted delivery of therapeutic growth factors, with the aid of hydrogels, to bone and cartilage is a key to advance the field of regenerative medicine. In this review article, we propose five important aspects of therapeutic growth factor delivery for bone and cartilage regeneration: (1) protection of protein growth factors from physical and enzymatic degradation, (2) targeted growth factor delivery, (3) controlling GF release kinetics, (4) long-term stability of regenerated tissues, and (5) osteoimmunomodulatory effects of therapeutic growth factors and carriers\/scaffolds.<\/jats:p>","DOI":"10.3390\/gels9050377","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T01:33:36Z","timestamp":1683164016000},"page":"377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Optimizing Delivery of Therapeutic Growth Factors for Bone and Cartilage Regeneration"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5687-2989","authenticated-orcid":false,"given":"Eri","family":"Takematsu","sequence":"first","affiliation":[{"name":"Department of Surgery, Stanford Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Murphy","sequence":"additional","affiliation":[{"name":"Blond McIndoe Laboratories, School of Biological Science, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stanford Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8098-3753","authenticated-orcid":false,"given":"Holly","family":"Steininger","sequence":"additional","affiliation":[{"name":"School of Medicine, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stanford Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7149-041X","authenticated-orcid":false,"given":"Thomas H.","family":"Ambrosi","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of California, Davis, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles K. F.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stanford Medicine, Stanford, CA 94305, USA"},{"name":"Institute for Stem Cell Biology and Regenerative Medicine, Stanford Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,3]]},"reference":[{"key":"ref_1","unstructured":"a.I.S (2023, April 01). Global Burden of Disease 2019. Disease. Available online: https:\/\/www.healthdata.org\/results\/gbd_summaries\/2019\/osteoarthritis-level-3-cause."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"46","DOI":"10.5152\/eurjrheum.2016.048","article-title":"An overview and management of osteoporosis","volume":"4","year":"2017","journal-title":"Eur. J. Rheumatol."},{"key":"ref_3","unstructured":"Atala, A., and Allickson, J.G. (2015). Translational Regenerative Medicine, Academic Press."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"295","DOI":"10.5152\/balkanmedj.2014.13265","article-title":"Fracture history in osteoporosis: Risk factors and its effect on quality of life","volume":"31","author":"Kuru","year":"2014","journal-title":"Balkan Med. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/S0140-6736(97)07226-7","article-title":"Osteoarthritis","volume":"350","author":"Creamer","year":"1997","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1002\/art.23176","article-title":"Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part II","volume":"58","author":"Lawrence","year":"2008","journal-title":"Arthritis Rheumatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S0950-3579(97)80011-8","article-title":"Economics of osteoarthritis: A global perspective","volume":"11","author":"March","year":"1997","journal-title":"Baillieres Clin. Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nrendo.2011.146","article-title":"Antiresorptive therapies for osteoporosis: A clinical overview","volume":"8","author":"Chen","year":"2011","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.drudis.2013.07.015","article-title":"Treating osteoporosis by targeting parathyroid hormone to bone","volume":"19","author":"Ponnapakkam","year":"2014","journal-title":"Drug Discov. Today"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nrrheum.2016.65","article-title":"Ageing and the pathogenesis of osteoarthritis","volume":"12","author":"Loeser","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.jhsa.2014.11.026","article-title":"Management of osteoarthrosis of the thumb joints","volume":"40","author":"Berger","year":"2015","journal-title":"J. Hand Surg. Am."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Shakoor, S., Kibble, E., and El-Jawhari, J.J. (2022). Bioengineering Approaches for Delivering Growth Factors: A Focus on Bone and Cartilage Regeneration. Bioengineering, 9.","DOI":"10.3390\/bioengineering9050223"},{"key":"ref_13","unstructured":"Hasija, Y. (2021). Translational Biotechnology, Academic Press."},{"key":"ref_14","unstructured":"Nuventra (2023, April 01). Points to Consider in Drug Development of Biologics and Small Molecules. Available online: https:\/\/www.allucent.com\/resources\/blog\/points-consider-drug-development-biologics-and-small-molecules."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"327950","DOI":"10.1155\/2014\/327950","article-title":"Next generation delivery system for proteins and genes of therapeutic purpose: Why and how?","volume":"2014","author":"Sharma","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jconrel.2010.06.011","article-title":"The effects of carrier nature and pH on rhBMP-2-induced ectopic bone formation","volume":"147","author":"Luca","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.copbio.2014.07.007","article-title":"Mammalian cell-produced therapeutic proteins: Heterogeneity derived from protein degradation","volume":"30","author":"Dorai","year":"2014","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.2174\/1389450117666151209120139","article-title":"Delivery of Therapeutic Proteins: Challenges and Strategies","volume":"17","author":"Rehman","year":"2016","journal-title":"Curr. Drug Targets"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3389\/fphar.2015.00286","article-title":"Advances and Challenges of Liposome Assisted Drug Delivery","volume":"6","author":"Sercombe","year":"2015","journal-title":"Front. Pharmacol."},{"key":"ref_20","first-page":"1155","article-title":"Liposomes containing glycocholate as potential oral insulin delivery systems: Preparation, in vitro characterization, and improved protection against enzymatic degradation","volume":"6","author":"Niu","year":"2011","journal-title":"Int. J. Nanomed."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/srep00935","article-title":"Bone regeneration by polyhedral microcrystals from silkworm virus","volume":"2","author":"Matsumoto","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13036-020-0231-y","article-title":"Heparinized chitosan stabilizes the bioactivity of BMP-2 and potentiates the osteogenic efficacy of demineralized bone matrix","volume":"14","author":"Kim","year":"2020","journal-title":"J. Biol. Eng."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1111\/j.1365-2184.2011.00788.x","article-title":"Chitosan enhances mineralization during osteoblast differentiation of human bone marrow-derived mesenchymal stem cells, by upregulating the associated genes","volume":"44","author":"Mathews","year":"2011","journal-title":"Cell Prolif."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1096\/fba.2018-00023","article-title":"Structural determinants and genetic modifications enhance BMP2 stability and extracellular secretion","volume":"1","author":"Khattar","year":"2019","journal-title":"FASEB bioAdv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nchem.1573","article-title":"A heparin-mimicking polymer conjugate stabilizes basic fibroblast growth factor","volume":"5","author":"Nguyen","year":"2013","journal-title":"Nat. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"121117","DOI":"10.1016\/j.biomaterials.2021.121117","article-title":"Enhanced bone regeneration via spatiotemporal and controlled delivery of a genetically engineered BMP-2 in a composite Hydrogel","volume":"277","author":"Chen","year":"2021","journal-title":"Biomaterials"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/B978-0-12-416039-2.00024-0","article-title":"Chapter nine\u2014Fusions of Elastin-like Polypeptides to Pharmaceutical Proteins","volume":"Volume 502","author":"Wittrup","year":"2012","journal-title":"Methods in Enzymology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.4065\/83.9.1032","article-title":"Bisphosphonates: Mechanism of action and role in clinical practice","volume":"83","author":"Drake","year":"2008","journal-title":"Mayo Clin. Proc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1023\/A:1024445903306","article-title":"Imparting Bone Affinity to Glycoproteins Through the Conjugation of Bisphosphonates","volume":"20","author":"Gittens","year":"2003","journal-title":"Pharm. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1021\/mp8002368","article-title":"Improved Bone Delivery of Osteoprotegerin by Bisphosphonate Conjugation in a Rat Model of Osteoarthritis","volume":"6","author":"Doschak","year":"2009","journal-title":"Mol. Pharm."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Katsumi, H., Sano, J.-i., Nishikawa, M., Hanzawa, K., Sakane, T., and Yamamoto, A. (2015). Molecular Design of Bisphosphonate-Modified Proteins for Efficient Bone Targeting In Vivo. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135966"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jconrel.2011.09.096","article-title":"Synthesis, characterization and evaluation of bone targeting salmon calcitonin analogs in normal and osteoporotic rats","volume":"158","author":"Bhandari","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.freeradbiomed.2014.02.002","article-title":"Extracellular superoxide dismutase suppresses hypoxia-inducible factor-1\u03b1 in pancreatic cancer","volume":"69","author":"Sibenaller","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/208787a0","article-title":"Binding of Tetracyclines to Bone","volume":"208","author":"Perrin","year":"1965","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1007\/s13346-018-0561-1","article-title":"Bone-targeted delivery of simvastatin-loaded PEG-PLGA micelles conjugated with tetracycline for osteoporosis treatment","volume":"8","author":"Xie","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"702","DOI":"10.2353\/ajpath.2007.061251","article-title":"Molecular changes in the vasculature of injured tissues","volume":"171","author":"Ruoslahti","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1161\/HYPERTENSIONAHA.120.15554","article-title":"CAR (CARSKNKDC) Peptide Modified ReNcell-Derived Extracellular Vesicles as a Novel Therapeutic Agent for Targeted Pulmonary Hypertension Therapy","volume":"76","author":"Wang","year":"2020","journal-title":"Hypertension"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.ijpharm.2014.08.067","article-title":"Poly aspartic acid peptide-linked PLGA based nanoscale particles: Potential for bone-targeting drug delivery applications","volume":"475","author":"Jiang","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1002\/term.2371","article-title":"Loading of BMP-2-related peptide onto three-dimensional nano-hydroxyapatite scaffolds accelerates mineralization in critical-sized cranial bone defects","volume":"12","author":"Sun","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5759","DOI":"10.1021\/acsnano.5b07828","article-title":"Osteoblast-Targeting-Peptide Modified Nanoparticle for siRNA\/microRNA Delivery","volume":"10","author":"Sun","year":"2016","journal-title":"ACS Nano"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1016\/j.biomaterials.2012.01.033","article-title":"Polycaprolactone electrospun mesh conjugated with an MSC affinity peptide for MSC homing in vivo","volume":"33","author":"Shao","year":"2012","journal-title":"Biomaterials"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1080\/1061186X.2018.1464011","article-title":"Recent advances in kartogenin for cartilage regeneration","volume":"27","author":"Cai","year":"2019","journal-title":"J. Drug Target."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6324","DOI":"10.1016\/j.biomaterials.2011.05.017","article-title":"Targeted delivery of non-viral vectors to cartilage in vivo using a chondrocyte-homing peptide identified by phage display","volume":"32","author":"Pi","year":"2011","journal-title":"Biomaterials"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"36938","DOI":"10.1021\/acsami.0c10458","article-title":"Chondrocyte-Targeted MicroRNA Delivery by Engineered Exosomes toward a Cell-Free Osteoarthritis Therapy","volume":"12","author":"Liang","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.copbio.2016.02.029","article-title":"Local and targeted drug delivery for bone regeneration","volume":"40","author":"Newman","year":"2016","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Lai, B.S., and Juhas, M. (2019). Recent Advances in Aptamer Discovery and Applications. Molecules, 24.","DOI":"10.3390\/molecules24050941"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/nm.3791","article-title":"Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference\u2013based bone anabolic strategy","volume":"21","author":"Liang","year":"2015","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1055\/s-2007-963409","article-title":"Aptamer-based isolation and subsequent imaging of mesenchymal stem cells in ischemic myocard by magnetic resonance imaging","volume":"Volume 179","author":"Wiskirchen","year":"2007","journal-title":"R\u00f6Fo-Fortschritte auf dem Gebiet der R\u00f6ntgenstrahlen und der Bildgebenden Verfahren"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8707","DOI":"10.2147\/IJN.S223164","article-title":"Novel Aptamer-Functionalized Nanoparticles Enhances Bone Defect Repair By Improving Stem Cell Recruitment","volume":"14","author":"Wang","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1089\/nat.2012.0349","article-title":"Identification of an Aptamer Binding to Human Osteogenic-Induced Progenitor Cells","volume":"23","author":"Ardjomandi","year":"2013","journal-title":"Nucleic Acid Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1007\/s10895-011-0903-6","article-title":"DNA Aptamer Beacon Assay for C-Telopeptide and Handheld Fluorometer to Monitor Bone Resorption","volume":"21","author":"Bruno","year":"2011","journal-title":"J. Fluoresc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"eabf7820","DOI":"10.1126\/sciadv.abf7820","article-title":"Genetically engineered cell membrane\u2013coated nanoparticles for targeted delivery of dexamethasone to inflamed lungs","volume":"7","author":"Park","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2208781","DOI":"10.1002\/adma.202208781","article-title":"Stem Cell Membrane-Coated Microribbon Scaffolds Induce Regenerative Innate and Adaptive Immune Responses in a Critical-Size Cranial Bone Defect Model","volume":"35","author":"Su","year":"2023","journal-title":"Adv. Mater."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1002\/jbm.a.34974","article-title":"Acceleration of bone formation during fracture healing by injectable collagen powder and human basic fibroblast growth factor containing a collagen-binding domain from Clostridium histolyticum collagenase","volume":"102","author":"Saito","year":"2014","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1089\/ten.teb.2016.0280","article-title":"Design and Use of Chimeric Proteins Containing a Collagen-Binding Domain for Wound Healing and Bone Regeneration","volume":"23","author":"Addi","year":"2017","journal-title":"Tissue Eng. B Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.ymthe.2019.01.017","article-title":"Cartilage-Targeted IGF-1 Treatment to Promote Longitudinal Bone Growth","volume":"27","author":"Lui","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ferrari, M., Onuoha, S.C., Fossati-Jimack, L., Nerviani, A., Alves, P.L., Pagani, S., Deantonio, C., Colombo, F., Santoro, C., and Sblattero, D. (2021). Novel Bispecific Antibody for Synovial-Specific Target Delivery of Anti-TNF Therapy in Rheumatoid Arthritis. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.640070"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.biomaterials.2016.01.048","article-title":"Mesenchymal cells condensation-inducible mesh scaffolds for cartilage tissue engineering","volume":"85","author":"Kim","year":"2016","journal-title":"Biomaterials"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.1021\/bm3010897","article-title":"Growth factor binding on heparin mimetic peptide nanofibers","volume":"13","author":"Mammadov","year":"2012","journal-title":"Biomacromolecules"},{"key":"ref_60","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_61","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.reth.2020.10.002","article-title":"Heparin-conjugated collagen as a potent growth factor-localizing and stabilizing scaffold for regenerative medicine","volume":"15","author":"Ikegami","year":"2020","journal-title":"Regen. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/jbm.a.36212","article-title":"Dual growth factor-immobilized asymmetrically porous membrane for bone-to-tendon interface regeneration on rat patellar tendon avulsion model","volume":"106","author":"Kim","year":"2018","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.colsurfb.2016.12.041","article-title":"Improving osteogenesis of three-dimensional porous scaffold based on mineralized recombinant human-like collagen via mussel-inspired polydopamine and effective immobilization of BMP-2-derived peptide","volume":"152","author":"Zhou","year":"2017","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"620","DOI":"10.3389\/fbioe.2020.00620","article-title":"Immobilization of Growth Factors for Cell Therapy Manufacturing","volume":"8","author":"Brunck","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"977","DOI":"10.3390\/ma8030977","article-title":"Fibrin Hydrogel Based Bone Substitute Tethered with BMP-2 and BMP-2\/7 Heterodimers","volume":"8","author":"Siegenthaler","year":"2015","journal-title":"Materials"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1002\/jbm.a.32899","article-title":"TGF-\u03b23 immobilized PLGA-gelatin\/chondroitin sulfate\/hyaluronic acid hybrid scaffold for cartilage regeneration","volume":"95","author":"Fan","year":"2010","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e435","DOI":"10.1038\/am.2017.171","article-title":"Novel biomaterial strategies for controlled growth factor delivery for biomedical applications","volume":"9","author":"Wang","year":"2017","journal-title":"NPG Asia Mater."},{"key":"ref_68","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_69","doi-asserted-by":"crossref","first-page":"940860","DOI":"10.1155\/2014\/940860","article-title":"Immobilization of Murine Anti-BMP-2 Monoclonal Antibody on Various Biomaterials for Bone Tissue Engineering","volume":"2014","author":"Ansari","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"146311","DOI":"10.1016\/j.apsusc.2020.146311","article-title":"Surface functionalization of dual growth factor on hydroxyapatite-coated nanofibers for bone tissue engineering","volume":"520","author":"Udomluck","year":"2020","journal-title":"Appl. Surf. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1039\/C3TB20853B","article-title":"Chemical strategies for the presentation and delivery of growth factors","volume":"2","author":"Huskens","year":"2014","journal-title":"J. Mater. Chem. B"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Oliveira, \u00c9.R., Nie, L., Podstawczyk, D., Allahbakhsh, A., Ratnayake, J., Brasil, D.L., and Shavandi, A. (2021). Advances in Growth Factor Delivery for Bone Tissue Engineering. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020903"},{"key":"ref_73","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. B Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1038\/s41467-022-30103-2","article-title":"Transmembrane stem cell factor protein therapeutics enhance revascularization in ischemia without mast cell activation","volume":"13","author":"Takematsu","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.biomaterials.2011.10.007","article-title":"Chondrogenesis of hMSC in affinity-bound TGF-beta scaffolds","volume":"33","author":"Ruvinov","year":"2012","journal-title":"Biomaterials"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3260","DOI":"10.1016\/j.biomaterials.2008.04.025","article-title":"The effect of sulfation of alginate hydrogels on the specific binding and controlled release of heparin-binding proteins","volume":"29","author":"Freeman","year":"2008","journal-title":"Biomaterials"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1021\/acs.biomac.1c00241","article-title":"A Biomimetic Macroporous Hybrid Scaffold with Sustained Drug Delivery for Enhanced Bone Regeneration","volume":"22","author":"Lee","year":"2021","journal-title":"Biomacromolecules"},{"key":"ref_78","first-page":"148","article-title":"Controlled release of injectable liposomal in situ gel loaded with recombinant human bone morphogenetic protein-2 for the repair of alveolar bone clefts in rabbits","volume":"26","author":"Hassan","year":"2016","journal-title":"J. Liposome Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"878930","DOI":"10.1155\/2013\/878930","article-title":"Evaluation of a Thiolated Chitosan Scaffold for Local Delivery of BMP-2 for Osteogenic Differentiation and Ectopic Bone Formation","volume":"2013","author":"Bae","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1002\/term.2664","article-title":"Bone morphogenetic protein-2 release profile modulates bone formation in phosphorylated hydrogel","volume":"12","author":"Olthof","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1002\/mabi.201500245","article-title":"Long-Term Controlled Protein Release from Poly(Ethylene Glycol) Hydrogels by Modulating Mesh Size and Degradation","volume":"15","author":"Tong","year":"2015","journal-title":"Macromol. Biosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"791","DOI":"10.2147\/IJN.S152698","article-title":"Guided osteoporotic bone regeneration with composite scaffolds of mineralized ECM\/heparin membrane loaded with BMP2-related peptide","volume":"13","author":"Sun","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1002\/term.3070","article-title":"An easy long-acting BMP7 release system based on biopolymer nanoparticles for inducing osteogenic differentiation of adipose mesenchymal stem cells","volume":"14","author":"Chen","year":"2020","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1007\/s10439-020-02522-z","article-title":"Nanoparticle-Mediated TGF-\u03b2 Release from Microribbon-Based Hydrogels Accelerates Stem Cell-Based Cartilage Formation In Vivo","volume":"48","author":"Barati","year":"2020","journal-title":"Ann. Biomed. Eng."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jconrel.2014.11.003","article-title":"Release and bioactivity of bone morphogenetic protein-2 are affected by scaffold binding techniques in vitro and in vivo","volume":"197","author":"Suliman","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Minardi, S., Fernandez-Moure, J.S., Fan, D., Murphy, M.B., Yazdi, I.K., Liu, X., Weiner, B.K., and Tasciotti, E. (2020). Biocompatible PLGA-Mesoporous Silicon Microspheres for the Controlled Release of BMP-2 for Bone Augmentation. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12020118"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8465","DOI":"10.2147\/IJN.S272571","article-title":"Creation of Bony Microenvironment with Extracellular Matrix Doped-Bioactive Ceramics to Enhance Osteoblast Behavior and Delivery of Aspartic Acid-Modified BMP-2 Peptides","volume":"15","author":"Zhou","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ijpharm.2013.02.056","article-title":"A cell-free nanofiber composite scaffold regenerated osteochondral defects in miniature pigs","volume":"447","author":"Litvinec","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_89","first-page":"1417","article-title":"Effects of sequentially released BMP-2 and BMP-7 from PELA microcapsule-based scaffolds on the bone regeneration","volume":"7","author":"Li","year":"2015","journal-title":"Am. J. Transl. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ejpb.2016.12.021","article-title":"New scaffolds encapsulating TGF-\u03b23\/BMP-7 combinations driving strong chondrogenic differentiation","volume":"114","author":"Borrajo","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1038\/s41591-020-1013-2","article-title":"Articular cartilage regeneration by activated skeletal stem cells","volume":"26","author":"Murphy","year":"2020","journal-title":"Nat. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1359\/jbmr.2002.17.7.1219","article-title":"Melatonin at Pharmacologic Doses Increases Bone Mass by Suppressing Resorption Through Down-Regulation of the RANKL-Mediated Osteoclast Formation and Activation","volume":"17","author":"Koyama","year":"2002","journal-title":"J. Bone Miner. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"10063","DOI":"10.3390\/ijms140510063","article-title":"Melatonin Effects on Hard Tissues: Bone and Tooth","volume":"14","author":"Liu","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"120489","DOI":"10.1016\/j.ijpharm.2021.120489","article-title":"Scaffold-based osteogenic dual delivery system with melatonin and BMP-2 releasing PLGA microparticles","volume":"600","author":"Jarrar","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jconrel.2011.07.006","article-title":"Sequential release kinetics of two (gentamicin and BMP-2) or three (gentamicin, IGF-I and BMP-2) substances from a one-component polymeric coating on implants","volume":"156","author":"Strobel","year":"2011","journal-title":"J. Control. Release"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1359\/jbmr.2001.16.6.1004","article-title":"Expression of Osteoprotegerin, Receptor Activator of NF-\u03baB Ligand (Osteoprotegerin Ligand) and Related Proinflammatory Cytokines During Fracture Healing","volume":"16","author":"Kon","year":"2001","journal-title":"J. Bone Miner. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.biomaterials.2014.10.015","article-title":"Controlled dual delivery of BMP-2 and dexamethasone by nanoparticle-embedded electrospun nanofibers for the efficient repair of critical-sized rat calvarial defect","volume":"37","author":"Li","year":"2015","journal-title":"Biomaterials"},{"key":"ref_98","first-page":"182","article-title":"Alendronate promotes osteoblast differentiation and bone formation in ovariectomy-induced osteoporosis through interferon-\u03b2\/signal transducer and activator of transcription 1 pathway","volume":"15","author":"Ma","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/s41598-020-80608-3","article-title":"Sequential dual-drug delivery of BMP-2 and alendronate from hydroxyapatite-collagen scaffolds for enhanced bone regeneration","volume":"11","author":"Lee","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/S0142-9612(03)00564-7","article-title":"In vitro effects of combined and sequential delivery of two bone growth factors","volume":"25","author":"Raiche","year":"2004","journal-title":"Biomaterials"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.biomaterials.2016.08.023","article-title":"Sequential and sustained release of SDF-1 and BMP-2 from silk fibroin-nanohydroxyapatite scaffold for the enhancement of bone regeneration","volume":"106","author":"Shen","year":"2016","journal-title":"Biomaterials"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"206","DOI":"10.5966\/sctm.2015-0115","article-title":"Controlled Dual Growth Factor Delivery from Microparticles Incorporated within Human Bone Marrow-Derived Mesenchymal Stem Cell Aggregates for Enhanced Bone Tissue Engineering via Endochondral Ossification","volume":"5","author":"Dang","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.joca.2006.07.006","article-title":"Degradable hydrogel scaffolds for in vivo delivery of single and dual growth factors in cartilage repair","volume":"15","author":"Holland","year":"2007","journal-title":"Osteoarthr. Cartil."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.biomaterials.2017.11.011","article-title":"Rapid initiation of guided bone regeneration driven by spatiotemporal delivery of IL-8 and BMP-2 from hierarchical MBG-based scaffold","volume":"196","author":"Lin","year":"2019","journal-title":"Biomaterials"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3283","DOI":"10.1016\/j.actbio.2012.05.014","article-title":"Simultaneous regeneration of articular cartilage and subchondral bone induced by spatially presented TGF-beta and BMP-4 in a bilayer affinity binding system","volume":"8","author":"Witte","year":"2012","journal-title":"Acta Biomater."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"035021","DOI":"10.1088\/1748-605X\/abd1ba","article-title":"Gradient scaffold with spatial growth factor profile for osteochondral interface engineering","volume":"16","author":"Dorcemus","year":"2021","journal-title":"Biomed. Mater."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1042\/EBC20200130","article-title":"Strategies for inclusion of growth factors into 3D printed bone grafts","volume":"65","author":"Longoni","year":"2021","journal-title":"Essays Biochem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"6603","DOI":"10.1038\/s41598-017-06911-8","article-title":"BMP2-modified injectable hydrogel for osteogenic differentiation of human periodontal ligament stem cells","volume":"7","author":"Park","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.biotechadv.2016.12.006","article-title":"The bioink: A comprehensive review on bioprintable materials","volume":"35","author":"Hospodiuk","year":"2017","journal-title":"Biotechnol. Adv."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1159\/000313399","article-title":"Hypertrophy in mesenchymal stem cell chondrogenesis: Effect of TGF-beta isoforms and chondrogenic conditioning","volume":"192","author":"Mueller","year":"2010","journal-title":"Cells Tissues Organs"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"6425","DOI":"10.1016\/j.biomaterials.2011.05.033","article-title":"Enhanced MSC chondrogenesis following delivery of TGF-\u03b23 from alginate microspheres within hyaluronic acid hydrogels in vitro and in vivo","volume":"32","author":"Bian","year":"2011","journal-title":"Biomaterials"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.joca.2010.03.001","article-title":"Bone Morphogenetic Proteins and articular cartilage: To serve and protect or a wolf in sheep clothing\u2019s?","volume":"18","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e64513","DOI":"10.7554\/eLife.64513","article-title":"Chondrocytes in the resting zone of the growth plate are maintained in a Wnt-inhibitory environment","volume":"10","author":"Hallett","year":"2021","journal-title":"eLife"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/labinvest.2015.142","article-title":"Wnt signaling in cartilage development and diseases: Lessons from animal studies","volume":"96","author":"Usami","year":"2016","journal-title":"Lab. Investig."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Miyatake, K., Kumagai, K., Imai, S., Yamaguchi, Y., and Inaba, Y. (2020). Sclerostin inhibits interleukin-1\u03b2-induced late stage chondrogenic differentiation through downregulation of Wnt\/\u03b2-catenin signaling pathway. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0239651"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1152\/physrev.00031.2015","article-title":"Parathyroid Hormone-Related Protein, Its Regulation of Cartilage and Bone Development, and Role in Treating Bone Diseases","volume":"96","author":"Martin","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"257","DOI":"10.3109\/03008207.2014.925885","article-title":"Indian Hedgehog, a critical modulator in osteoarthritis, could be a potential therapeutic target for attenuating cartilage degeneration disease","volume":"55","author":"Zhou","year":"2014","journal-title":"Connect. Tissue Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1242\/dev.018044","article-title":"Indian hedgehog signals independently of PTHrP to promote chondrocyte hypertrophy","volume":"135","author":"Mak","year":"2008","journal-title":"Development"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13075-019-1895-x","article-title":"Ipriflavone attenuates the degeneration of cartilage by blocking the Indian hedgehog pathway","volume":"21","author":"Guo","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Yang, H., Zhang, M., Liu, Q., Zhang, H., Zhang, J., Lu, L., Xie, M., Chen, D., and Wang, M. (2019). Inhibition of Ihh Reverses Temporomandibular Joint Osteoarthritis via a PTH1R Signaling Dependent Mechanism. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153797"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"8372","DOI":"10.1038\/s41598-020-65448-5","article-title":"The effect of bone inhibitors on periosteum-guided cartilage regeneration","volume":"10","author":"Hsiao","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.actbio.2018.06.027","article-title":"Suppressing mesenchymal stem cell hypertrophy and endochondral ossification in 3D cartilage regeneration with nanofibrous poly(l-lactic acid) scaffold and matrilin-3","volume":"76","author":"Liu","year":"2018","journal-title":"Acta Biomater."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1089\/ten.tea.2017.0232","article-title":"The Immunomodulatory Role of BMP-2 on Macrophages to Accelerate Osteogenesis","volume":"24","author":"Wei","year":"2017","journal-title":"Tissue Eng. A"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"52294","DOI":"10.18632\/oncotarget.10561","article-title":"TGF-\u03b2 induces M2-like macrophage polarization via SNAIL-mediated suppression of a pro-inflammatory phenotype","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/j.bone.2010.12.023","article-title":"RANKL-independent human osteoclast formation with APRIL, BAFF, NGF, IGF I and IGF II","volume":"48","author":"Hemingway","year":"2011","journal-title":"Bone"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"110046","DOI":"10.1016\/j.msec.2019.110046","article-title":"Osteoinductive and anti-inflammatory properties of chitosan-based scaffolds for bone regeneration","volume":"105","author":"Fasolino","year":"2019","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1007\/s12274-020-2783-z","article-title":"Mesoporous silica rods with cone shaped pores modulate inflammation and deliver BMP-2 for bone regeneration","volume":"13","author":"Xu","year":"2020","journal-title":"Nano Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"4014","DOI":"10.1016\/j.bioactmat.2021.04.008","article-title":"Implantable blood clot loaded with BMP-2 for regulation of osteoimmunology and enhancement of bone repair","volume":"6","author":"Fan","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_129","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_130","doi-asserted-by":"crossref","first-page":"19408","DOI":"10.1039\/C9NR03975A","article-title":"Stimulation of bone formation by monocyte-activator functionalized graphene oxide in vivo","volume":"11","author":"Bordoni","year":"2019","journal-title":"Nanoscale"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Li, Y., Xu, C., and Lei, C. (2023). The Delivery and Activation of Growth Factors Using Nanomaterials for Bone Repair. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15031017"},{"key":"ref_132","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_133","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3389\/fcell.2019.00189","article-title":"A Revised Perspective of Skeletal Stem Cell Biology","volume":"7","author":"Ambrosi","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cell.2014.12.002","article-title":"Identification and Specification of the Mouse Skeletal Stem Cell","volume":"160","author":"Chan","year":"2015","journal-title":"Cell"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.cell.2018.07.029","article-title":"Identification of the Human Skeletal Stem Cell","volume":"175","author":"Chan","year":"2018","journal-title":"Cell"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.mce.2008.02.017","article-title":"Skeletal stem cells: Phenotype, biology and environmental niches informing tissue regeneration","volume":"288","author":"Tare","year":"2008","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1093\/rb\/rby013","article-title":"Bone tissue engineering via growth factor delivery: From scaffolds to complex matrices","volume":"5","author":"Zadpoor","year":"2018","journal-title":"Regen. Biomater."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"6097","DOI":"10.2147\/IJN.S249829","article-title":"Growth Factor and Its Polymer Scaffold-Based Delivery System for Cartilage Tissue Engineering","volume":"15","author":"Chen","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"6995","DOI":"10.1073\/pnas.1810692116","article-title":"Age-related inflammation triggers skeletal stem\/progenitor cell dysfunction","volume":"116","author":"Josephson","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s11914-017-0413-9","article-title":"Effects of Aging on Fracture Healing","volume":"15","author":"Clark","year":"2017","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/s41586-021-03795-7","article-title":"Aged skeletal stem cells generate an inflammatory degenerative niche","volume":"597","author":"Ambrosi","year":"2021","journal-title":"Nature"}],"container-title":["Gels"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2310-2861\/9\/5\/377\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:28:50Z","timestamp":1760124530000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2310-2861\/9\/5\/377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,3]]},"references-count":141,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["gels9050377"],"URL":"https:\/\/doi.org\/10.3390\/gels9050377","relation":{},"ISSN":["2310-2861"],"issn-type":[{"value":"2310-2861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,3]]}}}