title: Tailored design of electrospun composite nanofibers with staged release of multiple angiogenic growth factors for chronic wound healing.
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 1month. 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.
authors.affiliation: Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Huan-Ju
authors.initials: HJ
authors.lastname: Lai
authors.affiliation: Department of Plastic Surgery, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan.
authors.forename: Chen-Hsiang
authors.initials: CH
authors.lastname: Kuan
authors.affiliation: Department of Material Engineering, Tatung University, Taipei, Taiwan.
authors.forename: Hsi-Chin
authors.initials: HC
authors.lastname: Wu
authors.affiliation: Department of Material Engineering, Tatung University, Taipei, Taiwan.
authors.forename: Jui-Che
authors.initials: JC
authors.lastname: Tsai
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Tim-Mo
authors.initials: TM
authors.lastname: Chen
authors.affiliation: Sunmax Biotechnology Co. Ltd, Tainan, Taiwan.
authors.forename: Dar-Jen
authors.initials: DJ
authors.lastname: Hsieh
authors.affiliation: Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu, Taiwan; Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan. Electronic address: twwang@mx.nthu.edu.tw.
authors.forename: Tzu-Wei
authors.initials: TW
authors.lastname: Wang
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002908:Chronic Disease; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D048909:Diabetes Complications / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D005780:Gelatin / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008297:Male; D053761:Nanocomposites / Q000737:chemistry*; D057139:Nanofibers / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000293:injuries / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D043925:Angiogenesis Inducing Agents; D003692:Delayed-Action Preparations; D005780:Gelatin
keywords: Angiogenic growth factors; Controlled release; Electrospinning; Nanofiber; Skin tissue engineering