Recombinant human insulin‐like growth factor‐I stimulates in vitro matrix synthesis and cell proliferation in rabbit flexor tendon

Flexor tendons have an intrinsic ability for repair, with a capacity to metabolize matrix components and to proliferate. To identify factors with the potential of affecting those abilities, the effects of recombinant human insulinlike growth factor (rhIGF‐I), insulin and fetal calf serum (FCS) on the synthesis of proteoglycan, collagen, and non‐collagen protein and cell proliferation were investigated in short‐term explant cultures of the deep flexor tendon of the rabbit. Matrix synthesis and cell proliferation were stimulated dose dependently by rhIGF‐I at doses between 10 and 250 and at 10‐100 ng/ml, respectively, by insulin at 250–5,000 ng/ml, and by FCS at 2–15%. Estimated maximal stimulation (Emax) of up to three times the control value was observed with rhIGF‐I at 250 ng/ml. Maximal stimulation was observed at 5,000 ng/ml with insulin, and FCS at 15%. rhIGF‐I was more potent than insulin in stimulating protein synthesis and cell proliferation. The Emax of stimulation of proteoglycan and collagen synthesis by rhIGF‐I were two times that of FCS, and the Emax of cell proliferation by FCS was twice that of rhIGF‐I. Growth factors thus have the ability to stimulate matrix synthesis and cell proliferation in rabbit flexor tendon. This provides a rationale for further studies on the role of growth factors in flexor tendon healing in humans.