Temporomandibular disorders (TMDs) are among the most common maxillofacial complaints and a major cause of orofacial pain. Although current treatments provide short- and long-term relief, alternative tissue engineering solutions are in great demand. Particularly, the development of strategies, providing long-term resolution of TMD to help patients regain normal function, is a high priority. An absolute prerequisite of tissue engineering is to understand normal structure and function. The current knowledge of anatomical, mechanical, and biochemical characteristics of the temporomandibular joint (TMJ) and associated tissues will be discussed, followed by a brief description of current TMD treatments. The main focus is on recent tissue engineering developments for regenerating TMJ tissue components, with or without a scaffold. The expectation for effectively managing TMD is that tissue engineering will produce biomimetic TMJ tissues that recapitulate the normal structure and function of the TMJ.

Frequent involvement of the disc in temporomandibular joint (TMJ) disorders warrants attempts to tissue engineer TMJ disc replacements. Physiologically, a great degree of similarity is seen between humans and farm pigs (FPs), but the pig's rapid growth confers a significant challenge for in vivo experiments. Minipigs have a slower growth rate and are smaller than FPs, but minipig TMJ discs have yet to be fully characterized. The objective of this study was to determine the suitability of the minipig for TMJ studies by extensive structural and functional characterization. The properties of minipig TMJ discs closely reproduced previously reported morphological, biochemical, and biomechanical values of human and FP discs. The width/length dimension ratio of the minipig TMJ disc was 1.95 (1.69 for human and 1.94 for FP). The biochemical evaluation revealed, on average per wet weight, 24.3% collagen (22.8% for human and 24.9% for FP); 0.8% glycosaminoglycan (GAG; 0.5% for human and 0.4% for FP); and 0.03% DNA (0.008% for human and 0.02% for FP). Biomechanical testing revealed, on average, compressive relaxation modulus of 50 kPa (37 kPa for human and 32 kPa for FP), compressive instantaneous modulus of 1121 kPa (1315 kPa for human and 1134 kPa for FP), and coefficient of viscosity of 13 MPa·s (9 MPa·s for human and 3 MPa·s for FP) at 20% strain. These properties also varied topographically in accordance to those of human and FP TMJ discs. Anisotropy, quantified by bidirectional tensile testing and histology, again was analogous among minipig, human, and FP TMJ discs. The minipig TMJ's ginglymoarthrodial nature was verified through cone beam computer tomography. Collectively, the similarities between minipig and human TMJ discs support the use of minipig as a relevant model for TMJ research; considering the practical advantages conferred by its growth rate and size, the minipig may be a preferred model over FP.

Scaffold-free systems have emerged as viable approaches for engineering load-bearing tissues. However, the tensile properties of engineered tissues have remained far below the values for native tissue. Here, by using self-assembled articular cartilage as a model to examine the effects of intermittent and continuous tension stimulation on tissue formation, we show that the application of tension alone, or in combination with matrix remodelling and synthesis agents, leads to neocartilage with tensile properties approaching those of native tissue. Implantation of tension-stimulated tissues results in neotissues that are morphologically reminiscent of native cartilage. We also show that tension stimulation can be translated to a human cell source to generate anisotropic human neocartilage with enhanced tensile properties. Tension stimulation, which results in nearly sixfold improvements in tensile properties over unstimulated controls, may allow the engineering of mechanically robust biological replacements of native tissue.