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采用层层组装实现生长因子的长期控制释放以构建组织工程血管。

Long-Term Controlled Growth Factor Release Using Layer-by-Layer Assembly for the Development of Tissue-Engineered Blood Vessels.

机构信息

Tissue Regeneration Department, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Drienerlolaan 5, Zuidhorst 145, 7522 NB Enschede, The Netherlands.

Faculty of Science, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.

出版信息

ACS Appl Mater Interfaces. 2022 Jun 29;14(25):28591-28603. doi: 10.1021/acsami.2c05988. Epub 2022 Jun 13.

Abstract

The development of a well-designed tissue-engineered blood vessel (TEBV) still remains a challenge. In recent years, approaches in which the host response to implanted biomaterials is used to generate vascular constructs within the patient's body have gained increasing interest. The delivery of growth factors to these -engineered vascular grafts might enhance myofibroblast recruitment and the secretion of essential extracellular matrix proteins, thereby optimizing their functional properties. Layer-by-layer (LbL) coating has emerged as an innovative technology for the controlled delivery of growth factors in tissue engineering applications. In this study, we combined the use of surface-etched polymeric rods with LbL coatings to control the delivery of TGF-β1, PDGF-BB, and IGF-1 and steer the foreign body response toward the formation of a functional vascular graft. Results showed that the regenerated tissue is composed of elastin, glycosaminoglycans, and circumferentially oriented collagen fibers, without calcification or systemic spill of the released growth factors. Functional controlled delivery was observed, whereas myofibroblast-rich tissue capsules were formed with enhanced collagen and elastin syntheses using TGF-β1 and TGF-β1/PDGF-BB releasing rods, when compared to control rods that were solely surface-engineered by chloroform etching. By combining our optimized LbL method and surface-engineered rods in an bioreactor approach, we could regulate the fate and ECM composition of -engineered vascular grafts to create a successful vascular tissue-engineered replacement.

摘要

设计良好的组织工程血管(TEBV)的开发仍然是一个挑战。近年来,利用宿主对植入生物材料的反应在患者体内生成血管结构的方法引起了越来越多的关注。将生长因子递送到这些 -工程血管移植物中可能会增强肌成纤维细胞的募集和必需细胞外基质蛋白的分泌,从而优化其功能特性。层层(LbL)涂层已成为组织工程应用中控制生长因子递送的创新技术。在这项研究中,我们将表面蚀刻聚合物棒与 LbL 涂层结合使用,以控制 TGF-β1、PDGF-BB 和 IGF-1 的递送,并引导异物反应形成功能性血管移植物。结果表明,再生组织由弹性蛋白、糖胺聚糖和周向排列的胶原纤维组成,没有钙化或释放的生长因子的全身溢出。与仅通过氯仿蚀刻表面工程化的对照棒相比,使用 TGF-β1 和 TGF-β1/PDGF-BB 释放棒观察到功能性的控制释放,形成富含肌成纤维细胞的组织胶囊,胶原和弹性蛋白合成增强。通过在生物反应器方法中结合我们优化的 LbL 方法和表面工程化棒,我们可以调节 -工程血管移植物的命运和 ECM 组成,以创建成功的血管组织工程替代物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2823/9247980/b35fc338ab38/am2c05988_0002.jpg

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