title: A novel controlled drug-delivery system for growth hormone applied to healing skin wounds in diabetic rats.
abstract: Controlled release systems for drugs, hormones and growth factors can be particularly useful in tissue repair processes. These systems act as a biodegradable support containing the substance to be delivered, allowing their gradual release. In the past years, the local application of growth factors has acquired special relevance as a therapeutic option for use in subjects who show deficient tissue scarring, the hormone dose being the limiting factor for its success. In this study, the in vitro biocompatibility of a copolymer formed by vinylpyrrolidone and 2-hydroxyethyl methacrylate, used as an administration vehicle for hGH, was evaluated. The system was then tested in vivo in terms of its capacity for healing incisional wounds in healthy and diabetic rats. For the in vitro studies, polymer and hormone degradation rates were determined, and polymer biocompatibility was evaluated in fibroblast cultures. In the in vivo experiments, an incision was made in the back of the animals, and polymers discs with/without hGH, were introduced in the aperture. Morphological, immunohistochemical and morphometric evaluations were performed on wound tissue specimens 3-10 days after surgery. In vitro, the polymer was found to be biodegradable and showed no toxic effects on fibroblasts, the hormone being slowly released to the culture medium. In untreated diabetic rats, a delayed skin scarring and cell response were observed, compared to that noted in healthy animals. Skin closure, keratinisation and fibrosis occurred earlier in the presence of the polymer-hGH system. The use of this co-polymer as an administration vehicle for hGH improves the wound scarring process in the pathological setting of diabetes.
authors.affiliation: Departamento de Ciencias Morfológicas y Cirugía, Facultad de Medicina, Universidad de Alcalá, Ctra N-II, Km 33.600, 28871 Alcalá de Henares, Madrid, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Gimeno
authors.forename: F
authors.initials: F
authors.lastname: García-Esteo
authors.forename: N
authors.initials: N
authors.lastname: García-Honduvilla
authors.forename: J
authors.initials: J
authors.lastname: San Román
authors.forename: J M
authors.initials: JM
authors.lastname: Bellón
authors.forename: J
authors.initials: J
authors.lastname: Buján
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002455:Cell Division; D002478:Cells, Cultured; D048909:Diabetes Complications; D016503:Drug Delivery Systems / Q000379:methods*; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D005347:Fibroblasts; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011108:Polymers / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D011108:Polymers; D019382:Human Growth Hormone; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9