Polymer Chemistry & Biomaterials Group - Centre of Macromolecular Chemistry (CMaC) - Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281, S4-Bis, 9000 Ghent, Belgium; Brussels Photonics (B-PHOT) - Department of Applied Physics and Photonics, Vrije Universiteit Brussel and Flanders Make, Pleinlaan 2, 1050 Brussels, Belgium.
Research Group 3D Printing and Biofabrication, Institute of Materials Science and Technology, TU Wien, Getreidemarkt 9, 1060 Vienna, Austria.
Acta Biomater. 2019 Oct 1;97:46-73. doi: 10.1016/j.actbio.2019.07.035. Epub 2019 Jul 22.
Over the recent decades gelatin has proven to be very suitable as an extracellular matrix mimic for biofabrication and tissue engineering applications. However, gelatin is prone to dissolution at typical cell culture conditions and is therefore often chemically modified to introduce (photo-)crosslinkable functionalities. These modifications allow to tune the material properties of gelatin, making it suitable for a wide range of biofabrication techniques both as a bioink and as a biomaterial ink (component). The present review provides a non-exhaustive overview of the different reported gelatin modification strategies to yield crosslinkable materials that can be used to form hydrogels suitable for biofabrication applications. The different crosslinking chemistries are discussed and classified according to their mechanism including chain-growth and step-growth polymerization. The step-growth polymerization mechanisms are further classified based on the specific chemistry including different (photo-)click chemistries and reversible systems. The benefits and drawbacks of each chemistry are also briefly discussed. Furthermore, focus is placed on different biofabrication strategies using either inkjet, deposition or light-based additive manufacturing techniques, and the applications of the obtained 3D constructs. STATEMENT OF SIGNIFICANCE: Gelatin and more specifically gelatin-methacryloyl has emerged to become one of the gold standard materials as an extracellular matrix mimic in the field of biofabrication. However, also other modification strategies have been elaborated to take advantage of a plethora of crosslinking chemistries. Therefore, a review paper focusing on the different modification strategies and processing of gelatin is presented. Particular attention is paid to the underlying chemistry along with the benefits and drawbacks of each type of crosslinking chemistry. The different strategies were classified based on their basic crosslinking mechanism including chain- or step-growth polymerization. Within the step-growth classification, a further distinction is made between click chemistries as well as other strategies. The influence of these modifications on the physical gelation and processing conditions including mechanical properties is presented. Additionally, substantial attention is put to the applied photoinitiators and the different biofabrication technologies including inkjet, deposition or light-based technologies.
在最近几十年中，明胶已被证明非常适合作为生物制造和组织工程应用的细胞外基质模拟物。然而，明胶在典型的细胞培养条件下容易溶解，因此经常进行化学修饰以引入（光）可交联官能团。这些修饰可以调整明胶的材料性能，使其适合广泛的生物制造技术，既可以作为生物墨水，也可以作为生物材料墨水（组分）。本综述提供了对不同报道的明胶修饰策略的非详尽概述，这些策略可产生可交联的材料，可用于形成适合生物制造应用的水凝胶。讨论并根据其机制（包括链增长和逐步聚合）对不同的交联化学进行了分类。逐步聚合机制进一步根据特定的化学分类，包括不同的（光）点击化学和可逆系统。还简要讨论了每种化学的优缺点。此外，重点放在使用喷墨、沉积或基于光的添加剂制造技术的不同生物制造策略上，以及获得的 3D 结构的应用。
明胶，特别是明胶-甲基丙烯酰，已成为生物制造领域细胞外基质模拟物的黄金标准材料之一。然而，还制定了其他修饰策略来利用多种交联化学。因此，提出了一篇专注于明胶的不同修饰策略和加工的综述文章。特别注意每种交联化学的基础化学以及每种类型交联化学的优缺点。根据其基本交联机制（包括链增长或逐步聚合）对不同策略进行了分类。在逐步聚合分类中，进一步区分了点击化学以及其他策略。介绍了这些修饰对物理凝胶化和加工条件（包括机械性能）的影响。此外，还特别关注应用的光引发剂和不同的生物制造技术，包括喷墨、沉积或基于光的技术。
