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Thiol-Rich Multifunctional Macromolecular Crosslinker for Gelatin-Norbornene-Based Bioprinting
Biomacromolecules ( IF 5.5 ) Pub Date : 2021-05-31 , DOI: 10.1021/acs.biomac.1c00421
Cailing Zhao 1 , Zejia Wu 2 , Hanyu Chu 2 , Tao Wang 3, 4 , Shuai Qiu 3 , Jing Zhou 1 , Qingtang Zhu 3, 4 , Xiaolin Liu 3 , Daping Quan 1 , Ying Bai 1, 4
Affiliation  

Extrusion-based bioprinting is an emerging and most frequently used technique for the fabrication of cell-laden constructs. A suitable hydrogel-based bioink for cell encapsulation and protection is critical for printability, structural stability, and post-printing cell viability. The thiol–ene chemistry-based gelatin-norbornene (GelNB) hydrogels have drawn much attention as a promising substitution of gelatin methacryloyl (GelMA), owing to the fast and controllable step-growth polymerization mechanism, as well as a significant reduction in reactive oxygen species (ROS) accumulation. Herein, thiolated heparin (HepSH) was synthesized and used as a macromolecular crosslinker for GelNB-based bioprinting, so that GelNB gelation became less sensitive to the thiol/ene ratio. The mechanical stability and moduli of GelNB/HepSH hydrogels were easily manipulated by the concentration and/or degree of thiol substitution. The GelNB/HepSH hydrogel allowed little intracellular ROS for encapsulated cells but provided vascular endothelial growth factor binding affinity for potential facilitation of neovascularization. Finally, the GelNB/HepSH bioink enabled a convenient printing process for both complex-structured bioscaffolds and cell-laden constructs, and resulted in good printability and high post-crosslinking cell viability. The crosslinker HepSH may serve as a multifunctional macromolecule that enables GelNB-based bioprinting in broad applications in regenerative medicine.

中文翻译:

用于基于明胶降冰片烯生物打印的富含硫醇的多功能高分子交联剂

基于挤压的生物打印是一种新兴且最常用的技术,用于制造载有细胞的结构。用于细胞封装和保护的合适的基于水凝胶的生物墨水对于可印刷性、结构稳定性和印刷后细胞活力至关重要。基于硫醇 - 烯化学的明胶 - 降冰片烯(GelNB)水凝胶作为明胶甲基丙烯酰(GelMA)的有前途的替代品引起了广泛关注,因为它具有快速可控的逐步增长聚合机制,以及活性氧的显着减少物种(ROS)积累。在此,合成了硫醇化肝素 (HepSH) 并将其用作基于 GelNB 的生物打印的大分子交联剂,因此 GelNB 凝胶化对硫醇/烯比变得不那么敏感。GelNB/HepSH 水凝胶的机械稳定性和模量很容易通过硫醇取代的浓度和/或程度来控制。GelNB/HepSH 水凝胶允许封装细胞的细胞内 ROS 很少,但提供血管内皮生长因子结合亲和力以促进新血管形成。最后,GelNB/HepSH bioink 为复杂结构的生物支架和载有细胞的构建体提供了方便的打印过程,并产生了良好的可打印性和高交联后细胞活力。交联剂 HepSH 可作为多功能大分子,使基于 GelNB 的生物打印在再生医学中的广泛应用成为可能。GelNB/HepSH 水凝胶允许封装细胞的细胞内 ROS 很少,但提供血管内皮生长因子结合亲和力以促进新血管形成。最后,GelNB/HepSH bioink 为复杂结构的生物支架和载有细胞的构建体提供了方便的打印过程,并产生了良好的可打印性和高交联后细胞活力。交联剂 HepSH 可作为多功能大分子,使基于 GelNB 的生物打印在再生医学中的广泛应用成为可能。GelNB/HepSH 水凝胶允许封装细胞的细胞内 ROS 很少,但提供血管内皮生长因子结合亲和力以促进新血管形成。最后,GelNB/HepSH bioink 为复杂结构的生物支架和载有细胞的构建体提供了方便的打印过程,并产生了良好的可打印性和高交联后细胞活力。交联剂 HepSH 可作为多功能大分子,使基于 GelNB 的生物打印在再生医学中的广泛应用成为可能。并导致良好的印刷适性和高交联后细胞活力。交联剂 HepSH 可作为多功能大分子,使基于 GelNB 的生物打印在再生医学中的广泛应用成为可能。并导致良好的印刷适性和高交联后细胞活力。交联剂 HepSH 可作为多功能大分子,使基于 GelNB 的生物打印在再生医学中的广泛应用成为可能。
更新日期:2021-06-14
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