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


METHODS
24 adult New Zealand White rabbits.


METHODS
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
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.


CONCLUSIONS
This technique may be of value for treating human patients at risk for delayed bone healing because of prior radiation therapy.
Ehrhart
Nicole P
NP
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1601, USA.
Hong
Liu
L
Morgan
Abby L
AL
Eurell
JoAnn A
JA
Jamison
Russell D
RD
D000287:Administration, Topical; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D003692:Delayed-Action Preparations; D006652:Histological Techniques / Q000662:veterinary; D020100:Hydrogels; D007091:Image Processing, Computer-Assisted; D011817:Rabbits / Q000502:physiology* / Q000601:surgery; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D014457:Ulna / Q000187:drug effects* / Q000293:injuries / Q000528:radiation effects
D003692:Delayed-Action Preparations; D020100:Hydrogels; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1