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Effect of sustained-release PDGF and TGF-beta on cyclophosphamide-induced impaired wound healing
Azra Ashraf1, Peter H U Lee, Kyoung Kim
1Chicago, Ill.; Boston and Worcester, Mass.; Los Angeles, Calif.; Ithaca, N.Y.; and Providence, R.I. From the Craniofacial Biology and Tissue Engineering Laboratory, Chicago Center for Plastic and Reconstructive Surgery, the Caritas Saint Elizabeth's Medical Center, Department of General Surgery, Tufts University Medical School, the Department of Biomedical Engineering and Mechanical and Aerospace Engineering, Cornell University, the University of Massachusetts Medical School, Center for Tissue Engineering, and Myomics.
Background:
Proper wound healing is pivotal to successful surgical outcomes. Previous studies have shown that growth factors can be used to enhance tissue repair under impaired healing conditions. However, because of limited delivery methods, the growth factors in these studies were delivered either topically or as a single local administration.
Methods:
Sixty Sprague-Dawley rats were divided equally into five groups and served as untreated normal controls or were implanted subcutaneously with a novel sustained-release drug delivery system through a dorsal incisional wound. This system delivered either transforming growth factor (TGF)-beta alone, platelet-derived growth factor (PDGF) alone, or TGF-beta and PDGF in combination, or served as unloaded sham controls. Wound healing was impaired in all treated rats by the administration of cyclophosphamide on days 1, 3, and 5. Wound tensile breaking strength was determined on days 4, 7, and 14.
Results:
Sustained release of either TGF-beta or PDGF alone not only failed to improve the healing of cyclophosphamide-induced impaired wound healing but resulted in a paradoxical decrease in wound tensile breaking strength by day 7. However, the combined delivery of both TGF-beta and PDGF improved wound healing and significantly increased wound tensile breaking strength by day 7.
Conclusions:
Sustained-release delivery of TGF-beta and PDGF in combination, but not separately, by a subcutaneously implanted drug delivery system significantly improves cyclophosphamide-induced impaired wound healing in rats.