Electrospun Fibers with Plasmid bFGF Polyplex Loadings Promote Skin Wound Healing in Diabetic Rats
Electrospun Fibers with Plasmid bFGF Polyplex Loadings Promote Skin Wound Healing in Diabetic Rats
复制标题
含有质粒 bFGF 复合物的电纺纤维促进糖尿病大鼠皮肤伤口愈合
DOI：
10.1021/mp200246b
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发表时间：
2012-01-01
影响因子：
4.9
通讯作者：
Li, Xiaohong
中科院分区：
文献类型：
--
作者：
Yang, Ye;Xia, Tian;Li, Xiaohong
由于缺乏引导细胞生长的支架，以及内源性生长因子水平和活性降低，深部或慢性皮肤创面很难自发愈合。结合DNA缩合技术的乳液电纺技术显示了逐步释放DNA的潜力，但在促进组织再生和伤口愈合方面的优势尚未得到阐明。在本研究中，将碱性成纤维细胞生长因子编码质粒(PbFGF)与聚乙二亚胺的复合体引入具有核-鞘结构的电纺纤维中，并在纤维鞘中加入聚乙二醇，使pbFGF得以持续释放4周。体外小鼠胚胎成纤维细胞实验表明，pbFGF纤维垫可通过自分泌bFGF促进细胞增殖，有效的细胞转染期超过28d。在糖尿病大鼠背部制造皮肤创面，用于体内评估被pbFGF负载的纤维垫覆盖后的皮肤再生。逐渐释放的pbFGF可显著提高创面愈合率，促进血管形成、胶原沉积和成熟、完全上皮化和皮肤附件的形成。以上结果表明，负载pbFGF的电纺纤维垫有可能用于促进糖尿病患者皮肤溃疡的愈合。
Deep or chronic skin wounds are difficult to heal spontaneously due to the lack of scaffold to guide cell growth and reduced levels and activities of endogenous growth factors. Emulsion electrospinning process integrated with DNA condensation techniques indicated potentials to gradually release DNA, but no attempt has been made to clarify the advantages in promoting tissue regeneration and wound recovery. In this study, polyplexes of basic fibroblast growth factor-encoding plasmid (pbFGF) with poly(ethylene imine) were incorporated into electrospun fibers with a core-sheath structure, and poly(ethylene glycol) was included into the fiber sheath to allow a sustained release of pbFGF for 4 weeks. In vitro tests on mouse embryo fibroblasts indicated that pbFGF-loaded fibrous mats enhanced cell proliferation by the autocrine bFGF, and an effective cell transfection proceeded for over 28 days. Skin wounds were created in the dorsal area of diabetic rats for in vivo evaluation of skin regeneration after being covered with pbFGF-loaded fibrous mats. The gradual pbFGF release revealed significantly higher wound recovery rate with improved vascularization, enhanced collagen deposition and maturation, complete re-epithelialization and formation of skin appendages. The above results demonstrate the potential use of pbFGF-loaded electrospun fibrous mats to accelerate the healing of skin ulcers for patients with diabetic mellitus.