title: Controlled release of thymosin beta 4 using a collagen-chitosan sponge scaffold augments cutaneous wound healing and increases angiogenesis in diabetic rats with hindlimb ischemia.
abstract: It is important to establish an efficient vascularization for the long-term acceptance of bioengineered skin equivalents treating the cutaneous wounds of diabetic rats with hindlimb ischemia. This study investigates the possible use of a collagen-chitosan sponge scaffold encapsulated with thymosin beta 4 (CCSS-eTβ4), an angiogenic factor, to accelerate cutaneous wound healing in streptozotocin (STZ)-induced diabetic rats with hindlimb ischemia. CCSSs-eTβ4 was fabricated using a freeze-drying method. The scaffolds were analyzed by scanning electron microscopy, swelling and degradation assays, mechanical properties, and scaffolds of 50:50 collagen-chitosan were selected and applied. The controlled release of Tβ4 from the scaffolds elicited localized and prolonged effects over 12 days, as shown by an enzyme-linked immunosorbent assay (ELISA). In vivo, CCSSs-eTβ4 improved diabetic cutaneous wound healing, with faster wound reepithelialization, better dermal reorganization, and higher wound vascularization. Furthermore, CCSSs-eTβ4 downregulated inflammatory genes and upregulated angiogenic genes in the wound tissue. Significant increases in CD31-positive endothelial cells and new vessel density were also observed. In vitro, Tβ4 increased the migratory and proliferative activity of high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). Meanwhile, we found that Tβ4 could promote HG-treated HUVECs migration and improve angiogenesis by activation of the VEGF/AKT pathway. Overall, these findings demonstrated the promising potential of CCSSs-eTβ4 to promote more effective wound healing and suggest its possible application for diabetic cutaneous wound treatment.
authors.affiliation: 1 Institute of Basic Medicine Science, College of Life Science, Chinese PLA General Hospital , Beijing, China .
authors.forename: Dongdong
authors.initials: D
authors.lastname: Ti
authors.forename: Haojie
authors.initials: H
authors.lastname: Hao
authors.forename: Lei
authors.initials: L
authors.lastname: Xia
authors.forename: Chuan
authors.initials: C
authors.lastname: Tong
authors.forename: Jiejie
authors.initials: J
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
authors.forename: Shenjun
authors.initials: S
authors.lastname: Xu
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhao
authors.forename: Huiling
authors.initials: H
authors.lastname: Liu
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D001458:Bandages; D001672:Biocompatible Materials / Q000138:chemical synthesis; D048271:Chitosan / Q000737:chemistry; D003094:Collagen / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis*; D017719:Diabetic Foot / Q000628:therapy*; D004058:Diffusion; D004867:Equipment Design; D019544:Equipment Failure Analysis; D008297:Male; D008422:Materials Testing; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017768:Skin, Artificial; D013947:Thymosin / Q000008:administration & dosage* / Q000737:chemistry; D054457:Tissue Scaffolds; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*; D000099201:Thymosin beta(4)
chemical_list: D043925:Angiogenesis Inducing Agents; D001672:Biocompatible Materials; D048271:Chitosan; D003094:Collagen; D003692:Delayed-Action Preparations; D013947:Thymosin; D000099201:Thymosin beta(4)