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基于可见光交联生物墨水形成多长度网络的负载基质细胞的人工角膜的 3D 生物打印。

3D bioprinting of stromal cells-laden artificial cornea based on visible light-crosslinkable bioinks forming multilength networks.

机构信息

Department of Biomaterials Science (BK21 Four Program), Pusan National University, Miryang 50463, Republic of Korea.

Department of Textile and Fibre Engineering, Indian Institute of Technology, Delhi 110016, India.

出版信息

Biofabrication. 2024 Apr 5;16(3). doi: 10.1088/1758-5090/ad35eb.

DOI:10.1088/1758-5090/ad35eb
PMID:38507802
Abstract

3D bioprinting has the potential for the rapid and precise engineering of hydrogel constructs that can mimic the structural and optical complexity of a healthy cornea. However, the use of existing light-activated bioinks for corneal printing is limited by their poor cytocompatibility, use of cytotoxic photoinitiators (PIs), low photo-crosslinking efficiency, and opaque/colored surface of the printed material. Herein, we report a fast-curable, non-cytotoxic, optically transparent bioprinting system using a new water-soluble benzoyl phosphinate-based PI and photocrosslinkable methacrylated hyaluronic acid (HAMA). Compared with commercially available PIs, the newly developed PI, lithium benzoyl (phenyl) phosphinate (BP), demonstrated increased photoinitiation efficiency under visible light and low cytotoxicity. Using a catalytic amount of BP, the HA-based bioinks quickly formed 3D hydrogel constructs under low-energy visible-light irradiation (405 nm, <1 J cm). The mechanical properties and printability of photocurable bioinks were further improved by blending low (10 kDa) and high (100 kDa) molecular weight (MW) HAMA by forming multilength networks. For potential applications as corneal scaffolds, stromal cell-laden dome-shaped constructs were fabricated using MW-blended HAMA/BP bioink and a digital light processing printer. The HA-based photocurable bioinks exhibited good cytocompatibility (80%-95%), fast curing kinetics (<5 s), and excellent optical transparency (>90% in the visible range), potentially making them suitable for corneal tissue engineering.

摘要

3D 生物打印具有快速精确地工程化水凝胶结构的潜力,这些结构可以模拟健康角膜的结构和光学复杂性。然而,现有的用于角膜打印的光激活生物墨水由于其较差的细胞相容性、使用细胞毒性光引发剂 (PIs)、低光交联效率以及打印材料的不透明/有色表面而受到限制。在此,我们报告了一种使用新型水溶性苯甲酰膦酸盐基 PI 和光交联性甲基丙烯酰化透明质酸 (HAMA) 的快速固化、非细胞毒性、光学透明的生物打印系统。与市售的 PI 相比,新开发的 PI,即锂苯甲酰 (苯基) 膦酸盐 (BP),在可见光下表现出更高的光引发效率和更低的细胞毒性。使用催化量的 BP,基于 HA 的生物墨水在低能量可见光照射(405nm,<1Jcm)下快速形成 3D 水凝胶结构。通过形成多长度网络,将低(10kDa)和高分子量(100kDa)HAMA 混合,可以进一步改善光固化生物墨水的机械性能和可打印性。为了将其潜在应用于角膜支架,使用 MW 混合 HAMA/BP 生物墨水和数字光处理打印机制造了负载间质细胞的穹顶状结构。基于 HA 的光固化生物墨水具有良好的细胞相容性(80%-95%)、快速固化动力学(<5s)和出色的光学透明度(>90%在可见光范围内),可能使其适用于角膜组织工程。

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