title: Syndesome Therapeutics for Enhancing Diabetic Wound Healing.
abstract: Chronic wounds represent a major healthcare and economic problem worldwide. Advanced wound dressings that incorporate bioactive compounds have great potential for improving outcomes in patients with chronic wounds but significant challenges in designing treatments that are effective in long-standing, nonhealing wounds. Here, an optimized wound healing gel was developed that delivers syndecan-4 proteoliposomes ("syndesomes") with fibroblast growth factor-2 (FGF-2) to enhance diabetic wound healing. In vitro studies demonstrate that syndesomes markedly increase migration of keratinocytes and fibroblasts isolated from both nondiabetic and diabetic donors. In addition, syndesome treatment leads to increased endocytic processing of FGF-2 that includes enhanced recycling of FGF-2 to the cell surface after uptake. The optimized syndesome formulation was incorporated into an alginate wound dressing and tested in a splinted wound model in diabetic, ob/ob mice. It was found that wounds treated with syndesomes and FGF-2 have markedly enhanced wound closure in comparison to wounds treated with only FGF-2. Moreover, syndesomes have an immunomodulatory effect on wound macrophages, leading to a shift toward the M2 macrophage phenotype and alterations in the wound cytokine profile. Together, these studies show that delivery of exogenous syndecan-4 is an effective method for enhancing wound healing in the long-term diabetic diseased state.
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, 78731, USA.
authors.forename: Subhamoy
authors.initials: S
authors.lastname: Das
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, 78731, USA.
authors.forename: Gunjan
authors.initials: G
authors.lastname: Singh
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, 78731, USA.
authors.forename: Marjan
authors.initials: M
authors.lastname: Majid
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Sherman
authors.affiliation: Division of Pharmacology and Toxicology, University of Texas at Austin, Austin, TX, 78731, USA.|Institute for Neuroscience, University of Texas at Austin, Austin, TX, 78731, USA.|Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, 78731, USA.
authors.forename: Somshuvra
authors.initials: S
authors.lastname: Mukhopadhyay
authors.affiliation: Diabetes Research Group, Department of Life Sciences and Institute for Applied Health Research, Glasgow Caledonian University, Glasgow, G4 0BA, UK.
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Wright
authors.affiliation: Diabetes Research Group, Department of Life Sciences and Institute for Applied Health Research, Glasgow Caledonian University, Glasgow, G4 0BA, UK.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Martin
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, 78731, USA.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Dunn
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, 78731, USA. abbaker@austin.utexas.edu.|Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, 78731, USA. abbaker@austin.utexas.edu.|The Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, TX, 78731, USA. abbaker@austin.utexas.edu.|Institute for Biomaterials, Drug Delivery and Regenerative Medicine, University of Texas at Austin, Austin, 78731, USA. abbaker@austin.utexas.edu.
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Baker
mesh_terms: D000818:Animals; D001458:Bandages; D048909:Diabetes Complications / Q000628:therapy*; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008820:Mice, Obese; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D016222:Fibroblast Growth Factor 2
keywords: diabetic ulcers; fibroblast growth factor-2; immunomodulation; syndecan-4; wound healing