Scaffold-Based Temporomandibular Joint Tissue Regeneration in Experimental Animal Models: A Systematic Review

Reconstruction of degenerated temporomandibular joint (TMJ) structures remains a clinical challenge. Tissue engineering (TE) is a promising alternative to current treatment options, where the TMJ is either left without functional components, or replaced with autogenous, allogeneic, or synthetic grafts. The objective of this systematic review was to answer the focused question: in experimental animal models, does the implantation of biomaterial scaffolds loaded with cells and/or growth factors (GFs) enhance regeneration of the discal or osteochondral TMJ tissues, compared with scaffolds alone, without cells, or GFs? Following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analysis) guidelines, electronic databases were searched for relevant controlled preclinical in vivo studies. Thirty studies reporting TMJ TE strategies in both small (rodents, rabbits; n = 25) and large animals (dogs, sheep, goats; n = 5) reporting histological and/or radiographic outcomes were included. Twelve studies reported ectopic (subcutaneous) implantation models in rodents, whereas 18 studies reported orthotopic, surgically induced defect models in large animals. On average, studies presented with an unclear-to-high risk of bias. In most studies, mesenchymal stem cells or chondrocytes were used in combination with either natural or synthetic polymer scaffolds, aiming for either TMJ disc or condyle regeneration. In summary, the overall preclinical evidence (ectopic [n = 6] and orthotopic TMJ models [n = 6]) indicate that addition of chondrogenic and/or osteogenic cells to biomaterial scaffolds enhances the potential for TMJ tissue regeneration. Standardization of animal models and quantitative outcome evaluations (biomechanical, biochemical, histomorphometric, and radiographic) in future studies, would allow more reliable comparisons and increase the validity of the results.