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载质粒 bFGF 的电纺纤维促进糖尿病大鼠皮肤伤口愈合。

Electrospun fibers with plasmid bFGF polyplex loadings promote skin wound healing in diabetic rats.

机构信息

Key Laboratory of Advanced Technologies of Materials, Ministry of Education of China, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China.

出版信息

Mol Pharm. 2012 Jan 1;9(1):48-58. doi: 10.1021/mp200246b. Epub 2011 Nov 28.

DOI:10.1021/mp200246b
PMID:22091745
Abstract

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.

摘要

深层或慢性皮肤创面由于缺乏支架来引导细胞生长和内源性生长因子水平和活性降低,难以自发愈合。乳剂静电纺丝工艺与 DNA 凝聚技术相结合显示出逐渐释放 DNA 的潜力,但尚未尝试阐明其在促进组织再生和创面恢复方面的优势。在这项研究中,碱性成纤维细胞生长因子(pbFGF)编码质粒的聚阳离子复合物(pbFGF)与聚(亚乙基亚胺)一起被纳入具有核壳结构的静电纺纤维中,并且聚乙二醇被包含在纤维鞘中,以允许 pbFGF 持续释放长达 4 周。对小鼠胚胎成纤维细胞的体外测试表明,pbFGF 负载的纤维垫通过自分泌 bFGF 增强了细胞增殖,并且有效的细胞转染持续了 28 天以上。在糖尿病大鼠背部区域制造皮肤创面,并用 pbFGF 负载的纤维垫覆盖,以评估体内皮肤再生。逐渐释放 pbFGF 显示出更高的创面恢复率,伴随着更好的血管生成、增强的胶原蛋白沉积和成熟、完全的再上皮化以及皮肤附属物的形成。上述结果表明,pbFGF 负载的静电纺纤维垫有可能加速糖尿病患者皮肤溃疡的愈合。

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