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

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 cartlage 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 regeneration in the mammalian limb, and leads to the appearance of ectopic growth plate cell architecture at adjacent sites.