Preclinical Animal Models for Temporomandibular Joint Tissue Engineering

Abstract

There is a paucity of in vivo studies that investigate the safety and efficacy of temporomandibular joint (TMJ) tissue regeneration approaches, in part due to the lack of established animal models. Review of disease models for study of TMJ is presented herein with an attempt to identify relevant preclinical animal models for TMJ tissue engineering, with emphasis on the disc and condyle. Although degenerative joint disease models have been mainly performed on mice, rats, and rabbits, preclinical regeneration approaches must employ larger animal species. There remains controversy regarding the preferred choice of larger animal models between the farm pig, minipig, goat, sheep, and dog. The advantages of the pig and minipig include their well characterized anatomy, physiology, and tissue properties. The advantages of the sheep and goat are their easier surgical access, low cost per animal, and its high tissue availability. The advantage of the dog is that the joint space is confined, so migration of interpositional devices should be less likely. However, each species has limitations as well. For example, the farm pig has continuous growth until about 18 months of age, and difficult surgical access due to the zygomatic arch covering the lateral aspect of joint. The minipig is not widely available and somewhat costly. The sheep and the goat are herbivores, and their TMJs mainly function in translation. The dog is a carnivore, and the TMJ is a hinge joint that can only rotate. Although no species provides the gold standard for all preclinical TMJ tissue engineering approaches, the goat and sheep have emerged as the leading options, with the minipig as the choice when cost is less of a limitation; and with the dog and farm pig serving as acceptable alternatives. Finally, naturally occurring TMJ disorders in domestic species may be harnessed on a preclinical trial basis as a clinically relevant platform for translation.

Evidence of vasculature and chondrocyte to osteoblast transdifferentiation in craniofacial synovial joints: Implications for osteoarthritis diagnosis and therapy

“…Therapies are directed toward either symptom management or highly invasive joint replacement surgeries with high failure rates . Here we show for the first time that the TMJ disk and condylar cartilage are vascularized in miniature pigs, a well‐established large animal that emulates human TMJ physiology and anatomy, and also in osteoarthritic human TMJ tissues. In osteoarthritic joints the vasculature architecture changes and is coupled with increased bone and evidence of cartilage to bone transformation, a phenomenon only shown until now in the TMJs of healthy growing rodents .…”

Temporomandibular Joint Hypofunction Secondary to Unilateral Partial Discectomy Attenuates Degeneration in Murine Mandibular Condylar Cartilage

“…Formative preclinical evaluation of novel therapeutics necessitates the utilization of preclinical animal models that encompass the unique mechanical and metabolic considerations of TMJ-OA 1,2,5) . The surgical instability, unilateral partial discectomy (UPD) murine model produces degenerative changes in the mandibular condylar cartilage that closely match their clinical presentation in humans 17,24,25) .…”

Remaining Hurdles for Tissue-Engineering the Temporomandibular Joint Disc

“…Signals such as biochemical and mechanical stimuli for mechanical improvement of the TMJ disc (Table 1) are also discussed. This section also examines small animal models that have been used for examining the performance of these implants [36,[39][40][41][42][43].…”

“…However, their small TMJ disc size limits studies to simple subcutaneous implantation as opposed to orthotopic studies in larger animals such as rabbits [43]. Moving toward orthotopic studies, rabbits allow for additional biochemical and histological analysis, and reliable mechanical testing [42], but present substantial differences from human size and loading conditions [43]. This motivates the use of large animal models that more closely resemble human anatomies and conditions [42].…”