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Effect of transforming growth factor-β1 on bone regeneration in critical-sized bone defects after irradiation of host tissues

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  • 1 Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1601.
  • | 2 Department of Facial and Reconstructive Surgery, College of Medicine, University of Illinois, Chicago, IL 60612.
  • | 3 Department of Material Sciences and Engineering, College of Engineering, University of Illinois, Urbana, IL 61802.
  • | 4 Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.
  • | 5 Department of Material Sciences and Engineering, College of Engineering, University of Illinois, Urbana, IL 61802.

Abstract

Objective—To determine whether sustained release of transforming growth factor (TGF)-β1 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 µg of adsorbed recombinant-human (rh) TGF-β1 was placed in the defect of 12 rabbits (6 irradiated and 6 nonirradiated), and the other 12 rabbits received hydrogel without rhTGF-β1. 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-β1–treated rabbits than in rabbits treated with hydrogel carrier alone. Local delivery of rhTGF-β1 via a hydrogel carrier in irradiated defects resulted in amounts of bone formation similar to those for nonirradiated defects treated by use of rhTGF-β1.

Conclusions and Clinical Relevance—Local delivery of TGF-β1 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. (Am J Vet Res 2005;66:1039–1045)

Abstract

Objective—To determine whether sustained release of transforming growth factor (TGF)-β1 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 µg of adsorbed recombinant-human (rh) TGF-β1 was placed in the defect of 12 rabbits (6 irradiated and 6 nonirradiated), and the other 12 rabbits received hydrogel without rhTGF-β1. 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-β1–treated rabbits than in rabbits treated with hydrogel carrier alone. Local delivery of rhTGF-β1 via a hydrogel carrier in irradiated defects resulted in amounts of bone formation similar to those for nonirradiated defects treated by use of rhTGF-β1.

Conclusions and Clinical Relevance—Local delivery of TGF-β1 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. (Am J Vet Res 2005;66:1039–1045)