A biodegradable copolymer for the slow release of growth hormone expedites scarring in diabetic rats.
In many diseases wound healing is impaired. This study was designed to establish whether the healing process in diabetes could be improved using a site-specific polymer delivery system containing hGH. The system was first optimized in in vitro experiments performed on cultured fibroblasts taken from healthy and diabetic rats and then tested in an incisional wound model created in the diabetic Wistar rat. In the in vitro experiments using cultured fibroblasts, cell viability, growth, and proliferation were determined, along with polymer degradation, hormone release rates and the expression of TGFbeta1 in the culture medium. For the in vivo experiments, polymer discs with/without GH were inserted through 3 cm incisions made on the backs of the animals. Wound specimens were obtained 7 and 30 days after surgery to evaluate inflammatory/apoptotic cells, metalloprotease expression and neoangiogenesis using microscopy and immunohistochemical techniques. The local administration of GH using a polymer delivery system did not affect the normal wound healing process. Conversely, when used in diabetic animals, epidermal and dermal repair was expedited. Our findings indicate that GH induces cell proliferation, enhances CD4(+) infiltration; increases extracellular matrix protein deposition; stimulates angiogenesis; and diminishes apoptosis at the diabetic wound site. These effects give rise to a comparable wound healing process to that observed in healthy animals.
García-Esteo
Francisco
F
Department of Medical Specialities, Faculty of Medicine, University of Alcala, Madrid, Spain.
Pascual
Gemma
G
Gallardo
Alberto
A
San-Román
Julio
J
Buján
Julia
J
Bellón
Juan Manuel
JM
D000818:Animals; D001672:Biocompatible Materials; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003692:Delayed-Action Preparations; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D066298:In Vitro Techniques; D008422:Materials Testing; D011102:Polyhydroxyethyl Methacrylate; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D014945:Wound Healing / Q000187:drug effects*
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D053773:Transforming Growth Factor beta1; D019382:Human Growth Hormone; D011102:Polyhydroxyethyl Methacrylate; D003094:Collagen