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一种双生长因子(GFs)功能化丝胶蛋白水凝胶的生物合成,用于促进糖尿病小鼠的慢性伤口愈合。

Biosynthesis of a dual growth factors (GFs) functionalized silk sericin hydrogel to promote chronic wound healing in diabetic mice.

作者信息

Deng Hanxin, Wang Fangyu, Zhou Yujuan, Lei Hexu, Zhou Hongji, Chen Siyu, Meng Zihan, He Mengyao, Tu Ding, Wang He, Li Xian, Xia Qingyou, Li Xueming, Wang Feng

机构信息

Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing, 400715, China.

Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, Department of Radiology, West China Second University Hospital, Sichuan University, 20# South Renmin Road, Chengdu, Sichuan, China.

出版信息

Bioact Mater. 2025 Jun 18;52:511-528. doi: 10.1016/j.bioactmat.2025.06.017. eCollection 2025 Oct.

Abstract

Chronic non-healing wounds, such as diabetic foot, pressure sores and bedsores have seriously affected the life quality of patients worldwide. GFs provide a potential solution to promote chronic wound healing by promoting cell proliferation and differentiation. However, limited resource, high cost, and instability greatly hindered their clinical applications. In present study, two silk gland bioreactor silkworm stains were generated to successfully synthesize functional silk fibers incorporating high expressions of EGF and PDGF-BB. The two GFs functionalized silk raw materials were used to fabricate a dual GFs sericin hydrogel (E/P-SH) delivering system with tunable material performances for better cell adhesion and biocompatibility, sustainable release of the dual GFs to synergistically promote cell proliferation and migration, which realized the significant healing of chronic full-thickness skin wound in diabetic mice within 12 days with more organized collagen arrangement and better epithelialization degree by reducing inflammatory response and promoting vascularization. These findings demonstrated that the biosynthesized dual GFs-SH delivering system provides an opportunity to broaden the wide utility of GFs in clinical treatment of diabetic wound healing.

摘要

慢性难愈合伤口,如糖尿病足、压疮和褥疮等,已严重影响全球患者的生活质量。生长因子(GFs)通过促进细胞增殖和分化,为促进慢性伤口愈合提供了一种潜在的解决方案。然而,资源有限、成本高昂以及稳定性差等问题极大地阻碍了它们的临床应用。在本研究中,构建了两种丝腺生物反应器家蚕品系,成功合成了含有高表达表皮生长因子(EGF)和血小板源性生长因子-BB(PDGF-BB)的功能性丝纤维。将这两种生长因子功能化的丝原料用于制备具有可调材料性能的双生长因子丝胶蛋白水凝胶(E/P-SH)递送系统,以实现更好的细胞黏附及生物相容性,双生长因子的可持续释放以协同促进细胞增殖和迁移,通过减轻炎症反应和促进血管生成,在12天内实现了糖尿病小鼠慢性全层皮肤伤口的显著愈合,且胶原排列更有序,上皮化程度更高。这些研究结果表明,生物合成的双生长因子-SH递送系统为拓宽生长因子在糖尿病伤口愈合临床治疗中的广泛应用提供了契机。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c75/12212160/33d3bce8a8b6/ga1.jpg

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