Continuous infusion of insulin-like growth factor-I into the epiphysis of the tibia

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Abstract
We have developed a method to promote longitudinal bone growth at the level of a specific growth-plate (GP) in young rabbits. Insulin-like growth factor-I (IGF-I) was continuously infused by means of an osmotic pump into the bone marrow cavity of the proximal epiphysis of the tibia. Radiological measurement showed a 2-mm overgrowth of the tibia after 4 weeks of treatment, while histological analysis demonstrated a 15% increase in the thickness of the selected GP. The local infusion of IGF-I increased the numbers of both proliferative and hypertrophic chondrocytes and promoted hyperplasia of bony trabeculae within the epiphysis. The distribution of material infused locally into the epiphysis was simulated by the infusion of Indian ink using the same methodology (osmotic pump) as that for IGF-I. Most of the dye remained within the bone marrow cavity of the epiphysis, but a portion infiltrated into the GP, reaching the deep layer of the physeal chondrocytes and primary spongiosa of the metaphysis. These results suggest that the method reported here is a valid one for delivering cytokines or growth factors to the selected GP and for controlling the growth and differentiation of physeal chondrocytes.