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3D 生物制造载细胞水凝胶血管的开发和用于体外血管成熟的低成本桌面打印灌注室。

Development of 3D Biofabricated Cell Laden Hydrogel Vessels and a Low-Cost Desktop Printed Perfusion Chamber for In Vitro Vessel Maturation.

机构信息

Institute of Biomaterials, Department of Material Science and Engineering, Friedrich-Alexander-University Erlangen-Nuremberg, Cauerstr. 6, 91058, Erlangen, Germany.

出版信息

Macromol Biosci. 2019 Sep;19(9):e1900245. doi: 10.1002/mabi.201900245. Epub 2019 Aug 6.

DOI:10.1002/mabi.201900245
PMID:31386277
Abstract

The vascular system represents the key supply chain for nutrients and oxygen inside the human body. Engineered solutions to produce sophisticated alternatives for autologous or artificial vascular implants to sustainably replace diseased vascular tissue still remain a key challenge in tissue engineering. In this paper, cell-laden 3D bioplotted hydrogel vessel-like constructs made from alginate di-aldehyde (ADA) and gelatin (GEL) are presented. The aim is to increase the mechanical stability of fibroblast-laden ADA-GEL vessels, tailoring them for maturation under dynamic cell culture conditions. BaCl is investigated as a crosslinker for the oxidized alginate-gelatin system. Normal human dermal fibroblast (NHDF)-laden vessel constructs are optimized successfully in terms of higher stiffness by increasing ADA concentration and using BaCl , with no toxic effects observed on NHDF. Contrarily, BaCl crosslinking of ADA-GEL accelerates cell attachment, viability, and growth from 7d to 24h compared to CaCl . Moreover, alignment of cells in the longitudinal direction of the hydrogel vessels when extruding the cell-laden hydrogel crosslinked with Ba is observed. It is possible to tune the stiffness of ADA-GEL by utilizing Ba as crosslinker. In addition, a customized, low-cost 3D printed polycarbonate (PC) perfusion chamber for perfusion of vessel-like constructs is introduced.

摘要

脉管系统代表了人体内营养物质和氧气的关键供应链。工程解决方案旨在生产复杂的替代物,用于自体或人工血管植入物,以可持续地替代病变的血管组织,这仍然是组织工程中的一个关键挑战。在本文中,提出了由藻酸钠二醛(ADA)和明胶(GEL)制成的负载细胞的 3D 生物打印水凝胶管状结构。目的是增加负载成纤维细胞的 ADA-GEL 血管的机械稳定性,使其能够在动态细胞培养条件下成熟。研究了 BaCl 作为氧化藻酸盐-明胶系统的交联剂。通过增加 ADA 浓度并用 BaCl 成功优化了负载正常人皮肤成纤维细胞(NHDF)的血管构建体,以获得更高的刚度,并且在 NHDF 上未观察到毒性作用。相比之下,与 CaCl 相比,BaCl 交联的 ADA-GEL 可加速细胞附着、活力和生长,从 7d 到 24h。此外,当挤出负载细胞的水凝胶与 Ba 交联时,观察到细胞在水凝胶血管的纵向方向上对齐。可以通过利用 Ba 作为交联剂来调整 ADA-GEL 的刚度。此外,还介绍了一种定制的、低成本的 3D 打印聚碳酸酯(PC)灌注室,用于灌注管状结构。

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