A biodegradable copolymer for the slow release of growth hormone expedites scarring in diabetic rats

Abstract

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.

Administration of the insulin into the scaffold atelocollagen for tissue‐engineered cartilage

“…Especially, we used the pellets without chondrocytes for this analysis, which might have yielded a difference in the insulin release. The usefulness of the collagen hydrogel for the carrier of drugs was shown in the applications for IFN‐α,29 IL‐2,30, 31 NGF,32–34 bFGF2, 35–38 and hGH 39. The present report has first showed that the atelocollagen hydrogel also works as the control release of insulin.…”

Peptide Hormone Regulation of Angiogenesis

“…The proangiogenic effects of GH have also been demonstrated in vivo. Treatment with GH increases the number of cerebral cortical arterioles in aging rats (515), augments VEGF expression and angiogenesis in the rat myocardium after infarction (302,468), stimulates wound angiogenesis in diabetic rats (191) and in mice (553), and may enhance vascularization by promoting mobilization ACTH 263 Adrenomedullin 460 Angiotensin II 236 Bradykinin 236 Calcitonin 89 Endothelin 218 Erythropoietin 23 Gastrin 212 Gonadotropins 457 Growth hormone/prolactin/placental lactogen 109 Growth hormone-releasing hormone 274 Insulin 270 IGF-I 129 Leptin 233 Neuropeptide Y 300 Oxytocin 79 Parathyroid hormone 389 Relaxin 202 Thrombopoietin 17 Thyroid-stimulating hormone 457 Vasopressin 13 of bone marrow-derived endothelial progenitor cells into the bloodstream (134,554). Consistent with these findings, the skin of adult, GH-deficient patients shows reduced capillary density and permeability that improves after treatment with GH (418), and GH-deficient adults and children have reduced retinal vascularization (238,239).…”

Human Growth Hormone Promotes Corneal Epithelial Cell Migration in Vitro

“…21 rHGH has been shown to be effective in closing cutaneous defects of the epithelium, accelerating wound healing, 21-23 activating epidermal and epithelial cell migration in burn victims, and assisting wound healing in diabetic rats. 24, 25 However, it is not known whether these effects of GH are mediated by IGF-1, and conflicting data have been reported regarding the roles of GH versus IGF-1 on the mechanism of increased cutaneous healing. For example, GH was reported to enhance human keratinocyte migration, promote human foreskin fibroblast expression of IGF-1 and stimulate fibroblast proliferation in vitro.…”