Riga Stradins University, Department of Pharmaceutical Chemistry, Riga, LV-1007, Latvia.
Baltic Biomaterials Centre of Excellence, Headquarters at Riga Technical University, Riga, LV-1048, Latvia.
Biomacromolecules. 2023 Jul 10;24(7):2957-2981. doi: 10.1021/acs.biomac.3c00098. Epub 2023 Jun 23.
Over the past two decades, hydrogels have come to the forefront of tissue engineering and regenerative medicine due to their biocompatibility, tunable degradation and low immunogenicity. Due to their porosity and polymeric network built up, it is possible to incorporate inside drugs, bioactive molecules, or other biochemically active monomers. Among biopolymers used for the fabrication of functional hydrogels, silk fibroin (SF) has received considerable research attention owing to its known biocompatibility and tunable range of mechanical properties. However, its relatively simple structure limits the potential usability. One of the emerging strategies is a chemical functionalization of SF, allowing for the introduction of methacrylate groups. This allows the versatile processing capability, including photo-cross-linking, which makes SF a useful polymer as a bioink for 3D printing. The methacrylation reaction has been done using numerous monomers such as methacrylic anhydride (MA), 2-isocyanatoethyl methacrylate (IEM), or glycidyl methacrylate (GMA). In this Review, we summarize the chemical functionalization strategies of SF materials and their resulting physicochemical properties. More specifically, a brief explanation of the different functionalization methods, the cross-linking principles, possibilities, and limitations of methacrylate compound functionalization are provided. In addition, we describe types of functional SF hydrogels and link their design principles to the performance in applications in the broad fields of biofabrication, tissue engineering, and regenerative medicine. We anticipate that the provided guidelines will contribute to the future development of SF hydrogels and their composites by providing the rational design of new mechanisms linked to the successful realization of targeted biomedical application.
在过去的二十年中，由于水凝胶的生物相容性、可调节的降解性和低免疫原性，它们已经成为组织工程和再生医学的前沿领域。由于其多孔性和聚合物网络结构，可以将药物、生物活性分子或其他生物化学活性单体掺入其中。在用于制造功能性水凝胶的生物聚合物中，丝素蛋白（SF）由于其已知的生物相容性和可调节的机械性能范围而受到了相当多的研究关注。然而，其相对简单的结构限制了其潜在的可用性。一种新兴的策略是对 SF 进行化学功能化，允许引入甲基丙烯酰基。这允许多功能的处理能力，包括光交联，这使得 SF 成为 3D 打印生物墨水的有用聚合物。已经使用了许多单体如甲基丙烯酰酐（MA）、2-异氰酸根合乙基甲基丙烯酸酯（IEM）或甲基丙烯酸缩水甘油酯（GMA）对 SF 进行了甲基丙烯酰化反应。在这篇综述中，我们总结了 SF 材料的化学功能化策略及其所得的物理化学性质。更具体地说，简要解释了不同的功能化方法、交联原理、可能性和局限性的甲基丙烯酰化合物的功能化。此外，我们还描述了功能性 SF 水凝胶的类型，并将其设计原理与其在生物制造、组织工程和再生医学等广泛领域中的应用性能联系起来。我们预计，所提供的指导方针将通过为与成功实现靶向生物医学应用相关的新机制的合理设计提供贡献，从而促进 SF 水凝胶及其复合材料的未来发展。
