The benefits and limitations of animal models for translational research in cartilage repair

Abstract

Much research is currently ongoing into new therapies for cartilage defect repair with new biomaterials frequently appearing which purport to have significant regenerative capacity. These biomaterials may be classified as medical devices, and as such must undergo rigorous testing before they are implanted in humans. A large part of this testing involves in vitro trials and biomechanical testing. However, in order to bridge the gap between the lab and the clinic, in vivo preclinical trials are required, and usually demanded by regulatory approval bodies. This review examines the in vivo models in current use for cartilage defect repair testing and the relevance of each in the context of generated results and applicability to bringing the device to clinical practice. Some of the preclinical models currently used include murine, leporine, ovine, caprine, porcine, canine, and equine models. Each of these has advantages and disadvantages in terms of animal husbandry, cartilage thickness, joint biomechanics and ethical and licencing issues. This review will examine the strengths and weaknesses of the various animal models currently in use in preclinical studies of cartilage repair.

Bone fracture healing in mechanobiological modeling: A review of principles and methods

“…Experimental methods work with real scenarios and generally provide results attributable to clinical applications. However, experimental methods require state of the art equipment, high accuracy, controlled conditions, high cost, and are often confounded by other factors such as unknown subject backgrounds, comorbidities, and genetic variation (Lacroix et al, 2002, Moran et al, 2016). On the other hand, computational modeling and simulation of the bone healing process have been utilized to overcome the limitations associated with experimental methods (Lacroix and Prendergast, 2002).…”

Animal Models for Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS): Achievements and Future Perspectives

“…The metabolic rate and regenerative capability of small animals are hardly comparable to humans and in addition, the systemic response to surgical intervention and the concomitant inflammatory processes may not resemble that observed in humans. In general, results of small animal-based research are hard to translate correctly to either human physiology or to the clinical situation, and undoubtedly there are serious limitations to be encountered [66,67,68]. …”

Preclinical models for orthopedic research and bone tissue engineering

“…Intramuscular implantation of bone forming agents has been associated with greater bone formation compared to subcutaneous sites . This has been attributed to factors such as the blood supply and local availability of osteoprogenitor cells, however may also be due to specific growth factors (myokines) produced by the muscle tissue . Alternatively, pellets can be implanted into the paraspinal musculature .…”

“…Specific attention is given to bone models that the authors have specific experience with. Preclinical orthopedic models of osteoporotic fractures, cartilage repair, tendon damage, and osteoarthritis are not specifically explored as these have been extensively reviewed elsewhere …”