{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:35:06Z","timestamp":1787027706727,"version":"build-2736575974"},"reference-count":111,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Medical Sciences, Univerity of Kragujevac, Serbia.","award":["JP 05\/22"],"award-info":[{"award-number":["JP 05\/22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Temporomandibular joint (TMJ) disorders represent chronic degenerative musculoskeletal conditions with a high prevalence in the general population and limited regenerative treatment options. Owing to the insufficient efficacy of current conservative and surgical therapies, there is a growing clinical need for biologically based regenerative approaches. Tissue engineering (TE), particularly scaffold-based strategies, has emerged as a promising avenue for TMJ regeneration. This systematic review analyzed preclinical in vivo studies investigating scaffold-based interventions for TMJ disc and osteochondral repair. A structured literature search of PubMed and Scopus databases identified 39 eligible studies. Extracted data included scaffold composition, use of cellular and bioactive components, animal models, and reported histological, radiological, and functional outcomes. Natural scaffolds, such as decellularized extracellular matrix and collagen-based hydrogels, demonstrated favorable biocompatibility and support for fibrocartilaginous regeneration, whereas synthetic materials including polycaprolactone, poly (lactic-co-glycolic acid), and polyvinyl alcohol provided superior mechanical stability and structural tunability. Cells were used in 17\/39 studies (43%); quantitative improvements were variably reported across these studies. Bioactive molecule delivery, including transforming growth factor-\u03b2, histatin-1, and platelet-rich plasma, further enhanced tissue regeneration, while emerging drug- and gene-delivery approaches showed potential for modulating local inflammation. Despite encouraging results, the reviewed studies exhibited substantial heterogeneity in experimental design, outcome measures, and animal models, limiting direct comparison and translational interpretation. Scaffold-based approaches show preclinical promise but heterogeneity in design and incomplete quantitative reporting limit definitive conclusions. Future research should emphasize standardized methodologies, long-term functional evaluation, and the use of clinically relevant large-animal models to facilitate translation toward clinical application. However, functional and biomechanical outcomes were inconsistently reported and rarely standardized, preventing robust conclusions regarding the relationship between structural regeneration and restoration of TMJ function.<\/jats:p>","DOI":"10.3390\/bioengineering13020169","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T10:56:34Z","timestamp":1769684194000},"page":"169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Scaffolds and Stem Cells Show Promise for TMJ Regeneration: A Systematic Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7590-4014","authenticated-orcid":false,"given":"Miljana","family":"Nedeljkovic","sequence":"first","affiliation":[{"name":"Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gvozden","family":"Rosic","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-2477","authenticated-orcid":false,"given":"Dragica","family":"Selakovic","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0671-3784","authenticated-orcid":false,"given":"Jovana","family":"Milanovic","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0718-7421","authenticated-orcid":false,"given":"Aleksandra","family":"Arnaut","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1039-1028","authenticated-orcid":false,"given":"Milica","family":"Vasiljevic","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1697-8380","authenticated-orcid":false,"given":"Nemanja","family":"Jovicic","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1306-1494","authenticated-orcid":false,"given":"Lidija","family":"Veljkovic","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6430-4562","authenticated-orcid":false,"given":"Pavle","family":"Milanovic","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4665-4566","authenticated-orcid":false,"given":"Momir","family":"Stevanovic","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1053\/j.sult.2007.02.002","article-title":"Anatomy of the temporomandibular joint","volume":"28","author":"Alomar","year":"2007","journal-title":"Semin. Ultrasound CT MRI"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s11914-016-0327-y","article-title":"Recent Tissue Engineering Advances for the Treatment of Temporomandibular Joint Disorders","volume":"14","author":"Aryaei","year":"2016","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1159\/000086197","article-title":"Soft tissue mechanics of the temporomandibular joint","volume":"180","author":"Sindelar","year":"2005","journal-title":"Cells Tissues Organs"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1177\/154405910808700406","article-title":"Degenerative disorders of the temporomandibular joint: Etiology, diagnosis, and treatment","volume":"87","author":"Tanaka","year":"2008","journal-title":"J. Dent. Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Steinbaum, S., Kelso, A., Dairi, N.F., Boucher, N.S., and Yu, W. (2024). Assessment of Condylar Changes in Patients with Degenerative Joint Disease of the TMJ After Stabilizing Splint Therapy: A Retrospective CBCT Study. Diagnostics, 14.","DOI":"10.3390\/diagnostics14202331"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1177\/0022034516653922","article-title":"The Evolution of TMD Diagnosis: Past, Present, Future","volume":"95","author":"Ohrbach","year":"2016","journal-title":"J. Dent. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1111\/jgs.15354","article-title":"Temporomandibular Joint Disorders in Older Adults","volume":"66","author":"Yadav","year":"2018","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.1039\/D3BM01687K","article-title":"Applications of hydrogels in tissue-engineered repairing of temporomandibular joint diseases","volume":"12","author":"Wang","year":"2024","journal-title":"Biomater. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.tripleo.2011.04.021","article-title":"Research diagnostic criteria for temporomandibular disorders: A systematic review of axis I epidemiologic findings","volume":"112","author":"Manfredini","year":"2011","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0266-4356(94)90052-3","article-title":"Is there a role for temporomandibular joint surgery?","volume":"32","author":"Dolwick","year":"1994","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1053\/joms.2001.24288","article-title":"Discectomy as an effective treatment for painful temporomandibular joint internal derangement: A 5-year clinical and radiographic follow-up","volume":"59","author":"Eriksson","year":"2001","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s12663-014-0686-9","article-title":"Costochondral Graft as Interpositional material for TMJ Ankylosis in Children: A Clinical Study","volume":"14","author":"Sharma","year":"2015","journal-title":"J. Maxillofac. Oral Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1053\/joms.2003.50112","article-title":"Comparison of 2 temporomandibular joint total joint prosthesis systems","volume":"61","author":"Wolford","year":"2003","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.archoralbio.2017.07.013","article-title":"A review of in-vitro fibrocartilage tissue engineered therapies with a focus on the temporomandibular joint","volume":"83","author":"Lowe","year":"2017","journal-title":"Arch. Oral Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5090","DOI":"10.7150\/thno.44270","article-title":"Biomechanically, structurally and functionally meticulously tailored polycaprolactone\/silk fibroin scaffold for meniscus regeneration","volume":"10","author":"Li","year":"2020","journal-title":"Theranostics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1089\/ten.teb.2017.0429","article-title":"Scaffold-Based Temporomandibular Joint Tissue Regeneration in Experimental Animal Models: A Systematic Review","volume":"24","author":"Helgeland","year":"2018","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e336","DOI":"10.1016\/j.jormas.2021.08.003","article-title":"Systematic review of studies on drug-delivery systems for management of temporomandibular-joint osteoarthritis","volume":"123","author":"Barry","year":"2022","journal-title":"J. Stomatol. Oral Maxillofac. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"111677","DOI":"10.1016\/j.msec.2020.111677","article-title":"Cartilage tissue engineering using injectable functionalized demineralized bone matrix scaffold with glucosamine in PVA carrier, cultured in microbioreactor prior to study in rabbit model","volume":"120","author":"Dadgar","year":"2021","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"025028","DOI":"10.1088\/1758-5090\/ab779f","article-title":"Entrapped in cage (EiC) scaffolds of 3D-printed polycaprolactone and porous silk fibroin for meniscus tissue engineering","volume":"12","author":"Cengiz","year":"2020","journal-title":"Biofabrication"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.actbio.2020.12.062","article-title":"Modeling of human intervertebral disc annulus fibrosus with complex multi-fiber networks","volume":"123","author":"Ghezelbash","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Desnica, J., Vujovic, S., Stanisic, D., Ognjanovic, I., Jovicic, B., Stevanovic, M., and Rosic, G. (2023). Preclinical Evaluation of Bioactive Scaffolds for the Treatment of Mandibular Critical-Sized Bone Defects: A Systematic Review. Appl. Sci., 13.","DOI":"10.3390\/app13084668"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Socorro, M., Dong, X., Trbojevic, S., Chung, W., Brown, B.N., and Almarza, A. (2025). The goat as a model for temporomandibular joint disc replacement: Techniques for scaffold fixation. Br. J. Oral Maxillofac. Surg., 91\u201397.","DOI":"10.1016\/j.bjoms.2024.10.233"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.actbio.2022.05.008","article-title":"Three-dimensional, biomimetic electrospun scaffolds reinforced with carbon nanotubes for temporomandibular joint disc regeneration","volume":"147","author":"Gan","year":"2022","journal-title":"Acta Biomater."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1002\/jbm.b.34629","article-title":"Acellular matrix hydrogel for repair of the temporomandibular joint disc","volume":"108","author":"Liang","year":"2020","journal-title":"J. Biomed. Mater. Res. Part B Appl. Biomater."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.morpho.2016.06.002","article-title":"Choosing sheep (Ovis aries) as animal model for temporomandibular joint research: Morphological, histological and biomechanical characterization of the joint disc","volume":"100","author":"Angelo","year":"2016","journal-title":"Morphologie"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1002\/term.3230","article-title":"A randomized controlled preclinical trial on 3 interposal temporomandibular joint disc implants: TEMPOJIMS\u2014Phase 2","volume":"15","author":"Wang","year":"2021","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.actbio.2023.01.042","article-title":"Decellularized-disc based allograft and xenograft prosthesis for the long-term precise reconstruction of temporomandibular joint disc","volume":"159","author":"Jiang","year":"2023","journal-title":"Acta Biomater."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chung, W.L., Brown, B.N., and Almarza, A.J. (2022). Decellularized small intestine submucosa device for temporomandibular joint meniscus repair: Acute timepoint safety study. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0273336"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Moura, C., Trindade, D., Vieira, M., Francisco, L., \u00c2ngelo, D.F., and Alves, N. (2020). Multi-Material Implants for Temporomandibular Joint Disc Repair: Tailored Additive Manufacturing Production. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00342"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"025003","DOI":"10.1088\/1758-5090\/8\/2\/025003","article-title":"Micro-precise spatiotemporal delivery system embedded in 3D printing for complex tissue regeneration","volume":"25","author":"Tarafder","year":"2016","journal-title":"Biofabrication"},{"key":"ref_31","first-page":"701","article-title":"A bioinspired and high-strengthed hydrogel for regeneration of perforated temporomandibular joint disc: Construction and pleiotropic immunomodulatory effects","volume":"20","author":"Xu","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wang, K.H., Chan, W.P., Chiu, L.H., Tsai, Y.H., Fang, C.L., Yang, C.B., Chen, K.C., Tsai, H.L., and Lai, W.F. (2017). Histological and Immunohistochemical Analyses of Repair of the Disc in the Rabbit Temporomandibular Joint Using a Collagen Template. Materials, 9.","DOI":"10.20944\/preprints201707.0023.v1"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1016\/j.transproceed.2004.05.049","article-title":"MRI and histology of collagen template disc implantation and regeneration in rabbit temporomandibular joint: Preliminary report","volume":"36","author":"Chan","year":"2004","journal-title":"Transplant. Proc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.ijom.2004.05.003","article-title":"Histological analysis of regeneration of temporomandibular joint discs in rabbits by using a reconstituted collagen template","volume":"34","author":"Lai","year":"2005","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"211","DOI":"10.2485\/jhtb.24.211","article-title":"Experimental Study on In Situ Tissue Engineering of the Temporomandibular Joint Disc using Autologous Bone Marrow and Collagen Sponge Scaffold","volume":"24","author":"Kobayashi","year":"2015","journal-title":"J. Hard Tissue Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e488","DOI":"10.1016\/j.joms.2011.02.130","article-title":"Extracellular matrix as an inductive template for temporomandibular joint meniscus reconstruction: A pilot study","volume":"69","author":"Brown","year":"2011","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1016\/j.joms.2011.12.030","article-title":"Inductive, scaffold-based, regenerative medicine approach to reconstruction of the temporomandibular joint disk","volume":"70","author":"Brown","year":"2012","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"20130287","DOI":"10.1098\/rsif.2013.0287","article-title":"Autologous adipose stem cells and polylactide discs in the replacement of the rabbit temporomandibular joint disc","volume":"29","author":"Ahtiainen","year":"2013","journal-title":"J. R. Soc. Interface"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/joor.13608","article-title":"Gelatin methacryloyl hydrogel with and without dental pulp stem cells for TMJ regeneration: An in vivo study in rabbits","volume":"51","author":"Monteiro","year":"2024","journal-title":"J. Oral Rehabil."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Du, Y., Chen, M., Jiang, J., Wang, L., Wu, G., and Feng, J. (2023). Hst1\/Gel-MA Scaffold Significantly Promotes the Quality of Osteochondral Regeneration in the Temporomandibular Joint. J. Funct. Biomater., 14.","DOI":"10.3390\/jfb14100513"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Shi, C., Yao, Y., Wang, L., Sun, P., Feng, J., and Wu, G. (2021). Human salivary histatin-1-functionalized gelatin methacrylate hydrogels promote the regeneration of cartilage and subchondral bone in temporomandibular joints. Pharmaceuticals, 14.","DOI":"10.3390\/ph14050484"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1089\/ten.tec.2023.0093","article-title":"Regenerative Engineering of a Biphasic Patient-Fitted Temporomandibular Joint Condylar Prosthesis","volume":"29","author":"Nedrelow","year":"2023","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"20417314241260436","DOI":"10.1177\/20417314241260436","article-title":"Delivery of dental pulp stem cells by an injectable ROS-responsive hydrogel promotes temporomandibular joint cartilage repair via enhancing anti-apoptosis and regulating microenvironment","volume":"15","author":"Ma","year":"2024","journal-title":"J. Tissue Eng."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.actbio.2020.12.056","article-title":"Cell-mediated injectable blend hydrogel-BCP ceramic scaffold for in situ condylar osteochondralrepai","volume":"123","author":"Wang","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.actbio.2020.11.031","article-title":"A bilayered scaffold with segregated hydrophilicity-hydrophobicity enables reconstruction of goat hierarchical temporomandibular joint condyle cartilage","volume":"121","author":"Yu","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"112721","DOI":"10.1016\/j.colsurfb.2022.112721","article-title":"Subchondral bone-inspired hydrogel scaffold for cartilage regeneration","volume":"218","author":"Guo","year":"2022","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Yang, Y., Huang, C., Zheng, H., Meng, Z., Heng, B.C., Zhou, T., Jiang, S., and Wei, Y. (2022). Superwettable and injectable GelMA-MSC microspheres promote cartilage repair in temporomandibular joints. Front. Bioeng. Biotechnol., 20.","DOI":"10.3389\/fbioe.2022.1026911"},{"key":"ref_48","first-page":"2969","article-title":"Co-culture of bone marrow stromal cells and chondrocytes in vivo for the repair of the goat condylar cartilage defects","volume":"16","author":"Sun","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.msec.2018.02.028","article-title":"Repair of full-thickness articular cartilage defect using stem cell-encapsulated thermogel","volume":"88","author":"Zhang","year":"2018","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"015004","DOI":"10.1088\/1748-605X\/ac367f","article-title":"Therapeutic application of 3B-PEG injectable hydrogel\/Nell-1 composite system to temporomandibular joint osteoarthritis","volume":"17","author":"Wang","year":"2021","journal-title":"Biomed. Mater."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.actbio.2021.04.010","article-title":"A 3D-printed PRP-GelMA hydrogel promotes osteochondral regeneration through M2 macrophage polarization in a rabbit model","volume":"128","author":"Jiang","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.joms.2011.07.004","article-title":"Distraction osteogenesis combined with tissue-engineered cartilage in the reconstruction of condylar osteochondral defect","volume":"69","author":"Yu","year":"2011","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.joca.2011.02.015","article-title":"NEL-like molecule-1-modified bone marrow mesenchymal stem cells\/poly lactic-co-glycolic acid composite improves repair of large osteochondral defects in mandibular condyle","volume":"19","author":"Zhu","year":"2011","journal-title":"Osteoarthr. Cartil."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e50","DOI":"10.1016\/j.joms.2010.12.049","article-title":"Osteochondral interface regeneration of rabbit mandibular condyle with bioactive signal gradients","volume":"69","author":"Dormer","year":"2011","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.ijom.2007.06.007","article-title":"Regeneration of articular cartilage defects in the temporomandibular joint of rabbits by fibroblast growth factor-2: A pilot study","volume":"36","author":"Takafuji","year":"2007","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1054\/bjom.2001.0720","article-title":"Regeneration of defects in the articular cartilage in rabbit temporomandibular joints by bone morphogenetic protein-2","volume":"40","author":"Suzuki","year":"2002","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1089\/ten.tec.2009.0564","article-title":"In vivo ultrasound-assisted tissue-engineered mandibular condyle: A pilot study in rabbits","volume":"16","author":"Uludag","year":"2010","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S1010-5182(02)00187-7","article-title":"The use of polylactic acid\/polyglycolic acid copolymer and gelatin sponge complex containing human recombinant bone morphogenetic protein-2 following condylectomy in rabbits","volume":"31","author":"Ueki","year":"2003","journal-title":"J. Cranio-Maxillofac. Surg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/549762","article-title":"Mesenchymal stem cells and platelet gel improve bone deposition within CAD-CAM custom-made ceramic HA scaffolds for condyle substitution","volume":"2013","author":"Ciocca","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1016\/j.actbio.2012.06.031","article-title":"Intra-articular controlled release of anti-inflammatory siRNA with biodegradable polymer microparticles ameliorates temporomandibular joint inflammation","volume":"8","author":"Mountziaris","year":"2012","journal-title":"Acta Biomater."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11160","DOI":"10.1038\/s41598-019-47486-w","article-title":"Improved efficacy of naproxen-loaded NLC for temporomandibular joint administration","volume":"9","author":"Guilherme","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"022003","DOI":"10.1088\/1748-605X\/abc0b3","article-title":"Click chemistry-based biopolymeric hydrogels for regenerative medicine","volume":"16","author":"Li","year":"2021","journal-title":"Biomed. Mater."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1080\/17435889.2025.2466414","article-title":"Smart self-healing hydrogel wound dressings for diabetic wound treatment","volume":"20","author":"Hu","year":"2025","journal-title":"Nanomedicine"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1039\/D3TB02355A","article-title":"Recent advances of hydrogels as smart dressings for diabetic wounds","volume":"12","author":"Wang","year":"2024","journal-title":"J. Mater. Chem. B."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1016\/j.biomaterials.2011.01.057","article-title":"An overview of tissue and whole organ decellularization processes","volume":"32","author":"Crapo","year":"2011","journal-title":"Biomaterials"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s10561-023-10112-1","article-title":"An overview of the production of tissue extracellular matrix and decellularization process","volume":"25","author":"Dehghani","year":"2024","journal-title":"Cell Tissue Bank"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ymeth.2015.03.005","article-title":"Methods of tissue decellularization used for preparation of biologic scaffolds and in vivo relevance","volume":"84","author":"Keane","year":"2015","journal-title":"Methods"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Nathan, K.G., Genasan, K., and Kamarul, T. (2023). Polyvinyl Alcohol-Chitosan Scaffold for Tissue Engineering and Regenerative Medicine Application: A Review. Mar. Drugs, 21.","DOI":"10.3390\/md21050304"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.matbio.2016.11.005","article-title":"Expression of adipokines in osteoarthritis osteophytes and their effect on osteoblasts","volume":"62","author":"Junker","year":"2017","journal-title":"Matrix Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.matbio.2015.06.003","article-title":"The extracellular matrix: Tools and insights for the \u201comics\u201d era","volume":"49","author":"Naba","year":"2016","journal-title":"Matrix Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"303","DOI":"10.5435\/JAAOS-21-05-303","article-title":"Cartilage regeneration","volume":"21","author":"Tuan","year":"2013","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"101336","DOI":"10.1016\/j.gendis.2024.101336","article-title":"Notch1 signaling regulates Sox9 and VEGFA expression and governs BMP2-induced endochondral ossification of mesenchymal stem cells","volume":"12","author":"Zou","year":"2024","journal-title":"Genes Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2303794","DOI":"10.1002\/adhm.202303794","article-title":"Intra-Articular Injectable Biomaterials for Cartilage Repair and Regeneration","volume":"13","author":"Kalairaj","year":"2024","journal-title":"Adv. Healthc. Mater."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1242\/dmm.016881","article-title":"Targets, models and challenges in osteoarthritis research","volume":"8","author":"Thysen","year":"2015","journal-title":"Dis. Model. Mech."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s40824-018-0138-6","article-title":"Injectable hydrogels delivering therapeutic agents for disease treatment and tissue engineering","volume":"22","author":"Lee","year":"2018","journal-title":"Biomater. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41413-021-00147-z","article-title":"Subchondral bone microenvironment in osteoarthritis and pain","volume":"9","author":"Hu","year":"2021","journal-title":"Bone Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1136\/annrheumdis-2020-218089","article-title":"Microenvironment in subchondral bone: Predominant regulator for the treatment of osteoarthritis","volume":"80","author":"Hu","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/nrrheum.2012.130","article-title":"Bone remodelling in osteoarthritis","volume":"8","author":"Burr","year":"2012","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.cden.2017.06.003","article-title":"Biomaterials for Craniofacial Bone Regeneration","volume":"61","author":"Thrivikraman","year":"2017","journal-title":"Dent. Clin. N. Am."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1089\/ten.tea.2011.0503","article-title":"Restoration of critical-size defects in the rabbit mandible using porous nanohydroxyapatite-polyamide scaffolds","volume":"18","author":"Guo","year":"2012","journal-title":"Tissue Eng. Part A"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1038\/nature04957","article-title":"The stem-cell niche as an entity of action","volume":"441","author":"Scadden","year":"2006","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1210\/endo.139.2.5751","article-title":"Interspecies differences in bone composition, density, and quality: Potential implications for in vivo bone research","volume":"139","author":"Aerssens","year":"1998","journal-title":"Endocrinology"},{"key":"ref_83","first-page":"416","article-title":"Effect of sex steroids on peak bone density of growing rabbits","volume":"255","author":"Gilsanz","year":"1988","journal-title":"Am. J. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s00256-005-0022-z","article-title":"Bone mineral measurements of subchondral and trabecular bone in healthy and osteoporotic rabbits","volume":"35","author":"Largo","year":"2006","journal-title":"Skelet. Radiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1177\/0022034510381501","article-title":"An interspecies comparison of the temporomandibular joint disc","volume":"90","author":"Kalpakci","year":"2011","journal-title":"J. Dent. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/0278-2391(94)90051-5","article-title":"An animal model for studying mechanisms in human temporomandibular joint disc derangement","volume":"52","author":"Mills","year":"1994","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1089\/ten.teb.2017.0341","article-title":"Preclinical Animal Models for Temporomandibular Joint Tissue Engineering","volume":"24","author":"Almarza","year":"2018","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1186\/s13018-019-1292-9","article-title":"The minipig as a potential model for pedicle screw fixation: Morphometry and mechanics","volume":"14","author":"Harper","year":"2019","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/0003-9969(86)90009-9","article-title":"Gross anatomy of the mandibular joint and masticatory muscles in the domestic pig (Sus scrofa)","volume":"31","author":"Strom","year":"1986","journal-title":"Arch. Oral Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1089\/ten.tec.2017.0149","article-title":"The Yucatan Minipig Temporomandibular Joint Disc Structure-Function Relationships Support Its Suitability for Human Comparative Studies","volume":"23","author":"Vapniarsky","year":"2017","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.11607\/jomi.6278","article-title":"Vertical Bone Augmentation Using Ring Technique with Three Different Materials in the Sheep Mandible Bone","volume":"33","author":"Jinno","year":"2018","journal-title":"Int. J. Oral Maxillofac. Implant."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.bjoms.2020.03.016","article-title":"Systematic scoping review of mandibular bone tissue engineering","volume":"58","author":"Basyuni","year":"2020","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Stevanovic, M., Selakovic, D., Vasovic, M., Ljujic, B., Zivanovic, S., Papic, M., Zivanovic, M., Milivojevic, N., Mijovic, M., and Tabakovic, S.Z. (2022). Comparison of Hydroxyapatite\/Poly(lactide-co-glycolide) and Hydroxyapatite\/Polyethyleneimine Composite Scaffolds in Bone Regeneration of pigs Mandibular Critical Size Defects: In Vivo Study. Molecules, 27.","DOI":"10.3390\/molecules27051694"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/jop.12113","article-title":"Articular cartilage degeneration in the contralateral non-surgical temporomandibular joint in mice with a unilateral partial discectomy","volume":"43","author":"Cohen","year":"2014","journal-title":"J. Oral Pathol. Med."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Sillmann, Y.M., Eber, P., Orbeta, E., Wilde, F., Gross, A.J., and Guastaldi, F.P.S. (2025). Milestones in Mandibular Bone Tissue Engineering: A Systematic Review of Large Animal Models and Critical-Sized Defects. J. Clin. Med., 14.","DOI":"10.3390\/jcm14082717"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e1801236","DOI":"10.1002\/adhm.201801236","article-title":"Tissue Engineering for the Temporomandibular Joint","volume":"8","author":"Acri","year":"2019","journal-title":"Adv. Healthc. Mater."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s44174-024-00183-3","article-title":"A Review of Additive Manufacturing in Tissue Engineering and Regenerative Medicine","volume":"3","author":"Culbreath","year":"2024","journal-title":"Biomed. Mater. Devices"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12938-025-01381-w","article-title":"Advances in 3D-printed scaffold technologies for bone defect repair: Materials, biomechanics, and clinical prospects","volume":"24","author":"Sun","year":"2025","journal-title":"Biomed. Eng. OnLine"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"6470","DOI":"10.1021\/acsabm.4c01923","article-title":"Redefining Medical Applications with Safe and Sustainable 3D Printing","volume":"8","author":"Khan","year":"2025","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1016\/j.jcms.2014.03.023","article-title":"Self-repair capability of surgically created incisions in TMJ disc: An experimental study on goats","volume":"42","author":"Lin","year":"2014","journal-title":"J. Craniomaxillofac. Surg."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0901-5027(05)80012-8","article-title":"Effect of experimental disc perforation in sheep temporomandibular joints","volume":"20","author":"Bosanquet","year":"1991","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/0278-2391(88)90335-7","article-title":"Osteoarthrosis of the temporomandibular joint following experimental disc perforation in Macaca fascicularis","volume":"46","author":"Helmy","year":"1988","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_103","first-page":"349","article-title":"Effect of disc perforation on the temporomandibular joint: An experimental study and review of the literature on a canine model","volume":"16","author":"Miyamoto","year":"2003","journal-title":"Jpn. J. Oral Diagn.\/Oral Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1089\/ten.tea.2021.0137","article-title":"Photoreactive Hydrogel Stiffness Influences Volumetric Muscle Loss Repair","volume":"28","author":"Basurto","year":"2022","journal-title":"Tissue Eng. Part A"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"7070","DOI":"10.1021\/acsabm.1c00688","article-title":"Highly Efficient Soluble Blue Delayed Fluorescent and Hyperfluorescent Organic Light-Emitting Diodes by Host Engineering","volume":"4","author":"Lee","year":"2021","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Patel, J.C., Shukla, M., and Shukla, M. (2025). From bench to bedside: Translating mesenchymal stem cell therapies through preclinical and clinical evidence. Front. Bioeng. Biotechnol., 13.","DOI":"10.3389\/fbioe.2025.1639439"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"103427","DOI":"10.1016\/j.ebiom.2021.103427","article-title":"Mesenchymal stem\/stromal cell-based therapy for the treatment of rheumatoid arthritis: An update on preclinical studies","volume":"69","author":"Bueren","year":"2021","journal-title":"EBioMedicine"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"122720","DOI":"10.1016\/j.biomaterials.2024.122720","article-title":"Efficiently directing differentiation and homing of mesenchymal stem cells to boost cartilage repair in osteoarthritis via a nanoparticle and peptide dual-engineering strategy","volume":"312","author":"Wu","year":"2025","journal-title":"Biomaterials"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/j.jcms.2018.11.025","article-title":"Bone marrow nucleated cell concentrate autograft in temporomandibular joint degenerative disorders: 1-year results of a randomized clinical trial","volume":"47","author":"Vaira","year":"2019","journal-title":"J. Cranio-Maxillofac. Surg."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.tips.2020.06.009","article-title":"Mesenchymal stem cell immunomodulation: Mechanisms and therapeutic potential","volume":"41","author":"Song","year":"2020","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Cesnik, A.B., and Svajger, U. (2024). The issue of heterogeneity of MSC-Based advanced therapy medicinal products\u2014A review. Front. Cell. Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1400347"}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/2\/169\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T11:13:12Z","timestamp":1769685192000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/2\/169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,29]]},"references-count":111,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["bioengineering13020169"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering13020169","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,29]]}}}