Effect of transforming growth factor-beta1 on bone regeneration in critical-sized bone defects after irradiation of host tissues

Abstract

Objective: To determine whether sustained release of transforming growth factor (TGF)-beta1 from a gelatin hydrogel would enhance bone regeneration in critical-sized long-bone defects and overcome inhibitory effects of preoperative irradiation.

Animals: 24 adult New Zealand White rabbits.

Procedure: Rabbits were allocated to 2 groups. Twelve rabbits received localized megavoltage radiation to the right ulna by use of a cobalt 60 teletherapy unit, and 12 rabbits received no irradiation. Then, a 1.5-cm defect was aseptically created in the right ulna of each rabbit. Gelatin hydrogel that contained 5 microg of adsorbed recombinant-human (rh)TGF-beta1 was placed in the defect of 12 rabbits (6 irradiated and 6 nonirradiated), and the other 12 rabbits received hydrogel without rhTGF-beta1. Rabbits were euthanatized 10 weeks after surgery. New bone formation within the defect was analyzed by use of nondecalcified histomorphometric methods. A 1-way ANOVA was used to compare differences among groups.

Results: New bone formation within the defect was significantly greater in TGF-beta1-treated rabbits than in rabbits treated with hydrogel carrier alone. Local delivery of rhTGF-beta1 via a hydrogel carrier in irradiated defects resulted in amounts of bone formation similar to those for nonirradiated defects treated by use of rhTGF-beta1.

Conclusions and clinical relevance: Local delivery of TGF-beta1 by use of a hydrogel carrier appears to have therapeutic potential for enhancing bone formation in animals after radiation treatments.

Impact for human medicine: This technique may be of value for treating human patients at risk for delayed bone healing because of prior radiation therapy.