Widespread and early tracheal cartilage regeneration by synchronous slow release of b-FGF and BMP-2.

Our previous studies have demonstrated that slow release of basic fibroblast growth factor (b-FGF) or bone morphogenetic protein 2 (BMP-2) induces cartilage regeneration. In the present study, we investigated whether synchronous slow release of b-FGF and BMP-2 would induce more widespread and earlier cartilage regeneration than that induced by each growth factor alone. A 1-cm defect was made in the mid-ventral portion of each of 10 consecutive tracheal rings. In four controls, the defect was left untreated. In the gelatin group (n = 4), empty gelatin sponge was implanted. In the b-FGF + BMP-2 group (n = 5), two gelatin sponges containing 100 microg of b-FGF or BMP-2 solution were implanted. After various periods, we euthanatized the dogs, and examined the implant sites. In the b-FGF + BMP-2 group, regenerated fibrous cartilage connected the host cartilage stumps and completely filled the defect between them at 1, 2, 3, and 12 months. Regenerated cartilage was covered by regenerated perichondrium originating from the host perichondrium, and showed neovascularization in the extracellular matrix. We succeeded in inducing more widespread and earlier cartilage regeneration using synchronous slow release of b-FGF and BMP-2 than that induced by release of each growth factor alone.