Biomechanical properties of skin in massive weight loss patients.

BACKGROUND: The aim of this study is to assess skin strength in MWL patients relative to control cosmetic abdominoplasty patients biophysically, biochemically, and histologically. Growing success of weight loss programs has brought about an increase in the MWL population. Skin quality is thought to be impaired by MWL, but there are no compelling studies that have fully addressed the structural mechanisms involved. METHODS: Skin from the medial and lateral abdomen was harvested fresh from patients undergoing cosmetic abdominoplasty (n = 6) or abdominal panniculectomy for MWL (n = 35), and burst strength was tested in the horizontal and vertical directions. Collagen content was measured, and histological studies were performed to assess epidermal and dermal thickness, vascularity as well as the morphology and density of the collagen fibers. RESULTS: In all groups, skin stretched horizontally was stronger than skin stretched vertically (p < 0.001). The skin of MWL patients was stronger medially compared to the skin of cosmetic patients. (p = 0.047) Newly formed collagen was diminished in MWL than that in the control group, but the results were not statistically significant. Epidermal thickness was significantly higher medially in MWL (p = 0.049). Elastin fibers were decreased in the MWL group, while dermal vascularity was higher in the MWL group. CONCLUSIONS: The skin of MWL patients demonstrated stronger mechanical parameters than that of cosmetic patients in the medial part of the abdomen; however, the decrease in elastic fibers associated with a decrease in newly formed collagen seemingly provides a contradiction. Skin changes with MWL merits further study to understand it more completely.

Age-dependent impairment of HIF-1alpha expression in diabetic mice: Correction with electroporation-facilitated gene therapy increases wound healing, angiogenesis, and circulating angiogenic cells.

Wound healing is impaired in elderly patients with diabetes mellitus. We hypothesized that age-dependent impairment of cutaneous wound healing in db/db diabetic mice: (a) would correlate with reduced expression of the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha) as well as its downstream target genes; and (b) could be overcome by HIF-1alpha replacement therapy. Wound closure, angiogenesis, and mRNA expression in excisional skin wounds were analyzed and circulating angiogenic cells (CACs) were quantified in db/db mice that were untreated or received electroporation-facilitated HIF-1alpha gene therapy. HIF-1alpha mRNA levels in wound tissue were significantly reduced in older (4-6 months) as compared to younger (1.5-2 months) db/db mice. Expression of mRNAs encoding the angiogenic cytokines vascular endothelial growth factor (VEGF), angiopoietin 1 (ANGPT1), ANGPT2, platelet-derived growth factor B (PDGF-B), and placental growth factor (PLGF) was also impaired in wounds of older db/db mice. Intradermal injection of plasmid gWIZ-CA5, which encodes a constitutively active form of HIF-1alpha, followed by electroporation, induced increased levels of HIF-1alpha mRNA at the injection site on day 3 and increased levels of VEGF, PLGF, PDGF-B, and ANGPT2 mRNA on day 7. CACs in peripheral blood increased 10-fold in mice treated with gWIZ-CA5. Wound closure was significantly accelerated in db/db mice treated with gWIZ-CA5 as compared to mice treated with empty vector. Thus, HIF-1alpha gene therapy corrects the age-dependent impairment of HIF-1alpha expression, angiogenic cytokine expression, and CACs that contribute to the age-dependent impairment of wound healing in db/db mice.