Tailored design of electrospun composite nanofibers with staged release of multiple angiogenic growth factors for chronic wound healing
Journal
Acta Biomaterialia
Journal Volume
10
Journal Issue
10
Pages
4156-4166
Date Issued
2014
Author(s)
Abstract
The objective of this research study is to develop a collagen (Col) and hyaluronic acid (HA) inter-stacking nanofibrous skin equivalent substitute with the programmable release of multiple angiogenic growth factors (vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and endothelial growth factor (EGF)) either directly embedded in the nanofibers or encapsulated in the gelatin nanoparticles (GNs) by electrospinning technology. The delivery of EGF and bFGF in the early stage is expected to accelerate epithelialization and vasculature sprouting, while the release of PDGF and VEGF in the late stage is with the aim of inducing blood vessels maturation. The physiochemical characterizations indicate that the Col-HA-GN nanofibrous membrane possesses mechanical properties similar to human native skin. The design of a particle-in-fiber structure allows growth factors for slow controlled release up to 1 month. Cultured on biodegradable Col-HA membrane with four kinds of growth factors (Col-HA w/4GF), endothelial cells not only increase in growth rate but also form a better network with a thread-like tubular structure. The therapeutic effect of Col-HA w/4GF membrane on streptozotocin (STZ)-induced diabetic rats reveals an accelerated wound closure rate, together with elevated collagen deposition and enhanced maturation of vessels, as revealed by Masson's trichrome stain and immunohistochemical analysis, respectively. From the above, the electrospun Col-HA-GN composite nanofibrous skin substitute with a stage-wise release pattern of multiple angiogenic factors could be a promising bioengineered construct for chronic wound healing in skin tissue regeneration. ? 2014 Acta Materialia Inc.
SDGs
Other Subjects
Biomechanics; Blood vessels; Cell culture; Cell engineering; Collagen; Electrospinning; Endothelial cells; Hyaluronic acid; Tissue; Tissue regeneration; Angiogenic growth factors; Basic fibroblast growth factor; Chronic wounds; Controlled release; Gelatin nanoparticles; Nano-fibrous; Platelet-derived growth factors; Skin tissue engineering; Vascular endothelial growth factor; Wound healing; Nanofibers; collagen; endothelial growth factor; fibroblast growth factor 2; gelatin; growth factor; hyaluronic acid; molecular scaffold; nanocomposite; nanofiber; nanoparticle; platelet derived growth factor; unclassified drug; vasculotropin; angiogenic factor; delayed release formulation; gelatin; nanocomposite; nanofiber; angiogenesis; animal experiment; animal model; animal tissue; Article; blood vessel; cell growth; chronic wound; confocal microscopy; controlled drug release; controlled study; drug delivery system; electrospinning; endothelium cell; epithelization; gene expression; growth rate; histology; human; human cell; in vitro study; male; membrane; nanoencapsulation; nonhuman; rat; scanning electron microscopy; scar formation; skin capillary; skin scar; streptozotocin-induced diabetes mellitus; tissue engineering; tissue regeneration; vascularization; wound closure; wound healing; animal; chemistry; chronic disease; delayed release formulation; Diabetes Complications; Diabetes Mellitus, Experimental; drug effects; injuries; metabolism; pathology; pharmacology; skin; Sprague Dawley rat; wound healing; Wounds and Injuries; Angiogenesis Inducing Agents; Animals; Chronic Disease; Delayed-Action Preparations; Diabetes Complications; Diabetes Mellitus, Experimental; Gelatin; Humans; Male; Nanocomposites; Nanofibers; Nanoparticles; Neovascularization, Physiologic; Rats; Rats, Sprague-Dawley; Skin; Wound Healing; Wounds and Injuries
Publisher
Elsevier Ltd
Type
journal article