Regeneration of growth plate cartilage induced in the neonatal rat hindlimb by reamputation

Abstract

Following primary hindlimb amputations dividing the lower femur or the central tibiofibula, the neonatal rat innately regenerates the distal growth plate(s) with a frequency of about 20-30%. One or two reamputation procedures were performed in an effort to increase the frequency of physeal regeneration, noting that such procedures, and related forms of tissue stimulation, have been repeatedly shown to induce regenerative growth at limb amputation sites of some amphibians that display little innate regenerative capacity. The present reamputation sequences divided the skeletal stump through the cartilaginous mass arising at its distal end. Following first reamputation an approximate three fold increase in the frequency of growth plate cartilage regeneration was observed at transfemoral and transtibiofibular sites. Only after second reamputation, however, did tibiofibular physeal cartilage regeneration equal in frequency that observed after first reamputation through the lower femur. Ectopic growth plate cell architecture was identified in cartilaginous extensions arising from the side of the distal femoral shaft, and also within the regrown secondary cartilage body, which unites the lower tibia and fibula in the shank of the rat. Moreover, among 3 of 11 femoral amputees that had sustained reamputations, regrowth of the distal femoral condylar mass and profile were achieved to varying degrees. It is concluded that a regimen of reamputation, known to induce regenerative growth in the amphibian limb, also induces skeletal regneration in the mammalian limb, and lead to the appearance of ectopic growth plate cell architecture at adjacent sites.

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

“…These models have limited potential in the determination of the clinical potential of new biomaterials as repair processes that are successful in restoring such small diameter defects may not be applicable in larger defect (Chu et al 2010a ). Rodents also have open growth plates throughout their maturity (Libbin & Rivera 1989 ) and therefore may have the increased intrinsic healing capacity of a juvenile. Additionally, the gait pattern and biomechanical loading environment in rodents varies significantly to that in humans.…”

Animal Models for Cartilage Regeneration and Repair

“…32 The thin cartilage is likely easier to damage, and may also be easier to repair than human articular cartilage. Although longitudinal assessment technologies may be limited for joints of this size, Watrin-Pinzano et al were able to evaluate spontaneous cartilage repair in rat patella with an 8.5 T magnetic resonance imaging (MRI) system.…”

In Vitro Effects of Bupivacaine on the Viability and Mechanics of Native and Engineered Cartilage Grafts

“…22 However, unlike humans, rodents can exhibit spontaneous articular cartilage repair because of lifelong open growth plates and thinner cartilage. 27,41 Another reason for the skepticism regarding the chondrotoxicity of anesthetics is that the majority of studies examining the toxic effects have been performed on monolayer culture, which does not adequately simulate in vivo conditions of chondrocytes embedded within the hyaline extracellular matrix (ECM). Some studies have suggested that an intact ECM may confer a protective effect against the toxicity of these agents.…”