Journal
TISSUE ENGINEERING PART A
Volume 21, Issue 3-4, Pages 541-549Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/ten.tea.2013.0750
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Funding
- National Basic Science and Development Program [2012CB518103, 2012CB518105]
- 863 Projects of Ministry of Science and Technology of China [2013AA020105, 2012AA020502]
- National Natural Science Foundation of China [81121004, 81230041]
- Key Sciences and Technology Project in Hainan province [ZDZX2013003]
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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-eT beta 4), an angiogenic factor, to accelerate cutaneous wound healing in streptozotocin (STZ)-induced diabetic rats with hindlimb ischemia. CCSSs-eT beta 4 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 T beta 4 from the scaffolds elicited localized and prolonged effects over 12 days, as shown by an enzyme-linked immunosorbent assay (ELISA). In vivo, CCSSs-eT beta 4 improved diabetic cutaneous wound healing, with faster wound reepithelialization, better dermal reorganization, and higher wound vascularization. Furthermore, CCSSs-eT beta 4 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, T beta 4 increased the migratory and proliferative activity of high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). Meanwhile, we found that T beta 4 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-eT beta 4 to promote more effective wound healing and suggest its possible application for diabetic cutaneous wound treatment.
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