Department of Biomedical Engineering, Michigan Technological University, Houghton, MI, 49931, USA.
Cardiovascular Division, Radcliff Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.
Adv Healthc Mater. 2023 Jul;12(17):e2203148. doi: 10.1002/adhm.202203148. Epub 2023 Feb 27.
Gelatin is a widely utilized bioprinting biomaterial due to its cell-adhesive and enzymatically cleavable properties, which improve cell adhesion and growth. Gelatin is often covalently cross-linked to stabilize bioprinted structures, yet the covalently cross-linked matrix is unable to recapitulate the dynamic microenvironment of the natural extracellular matrix (ECM), thereby limiting the functions of bioprinted cells. To some extent, a double network bioink can provide a more ECM-mimetic, bioprinted niche for cell growth. More recently, gelatin matrices are being designed using reversible cross-linking methods that can emulate the dynamic mechanical properties of the ECM. This review analyzes the progress in developing gelatin bioink formulations for 3D cell culture, and critically analyzes the bioprinting and cross-linking techniques, with a focus on strategies to optimize the functions of bioprinted cells. This review discusses new cross-linking chemistries that recapitulate the viscoelastic, stress-relaxing microenvironment of the ECM, and enable advanced cell functions, yet are less explored in engineering the gelatin bioink. Finally, this work presents the perspective on the areas of future research and argues that the next generation of gelatin bioinks should be designed by considering cell-matrix interactions, and bioprinted constructs should be validated against currently established 3D cell culture standards to achieve improved therapeutic outcomes.
明胶是一种广泛应用的生物打印生物材料，因其具有细胞黏附性和可酶切的特性，可改善细胞黏附和生长。明胶通常通过共价交联来稳定生物打印结构，但共价交联的基质无法再现天然细胞外基质（ECM）的动态微环境，从而限制了生物打印细胞的功能。在某种程度上，双网络生物墨水可以为细胞生长提供更类似于 ECM 的生物打印小生境。最近，人们正在使用可模拟 ECM 动态力学特性的可逆交联方法来设计明胶基质。本综述分析了用于 3D 细胞培养的明胶生物墨水配方的进展，并对生物打印和交联技术进行了批判性分析，重点是优化生物打印细胞功能的策略。本综述讨论了新的交联化学物质，这些物质可再现 ECM 的黏弹性、应力松弛微环境，并能够实现先进的细胞功能，但在工程化明胶生物墨水方面的研究还较少。最后，本文提出了未来研究的展望，并认为下一代明胶生物墨水的设计应考虑细胞-基质相互作用，并且生物打印构建体应根据目前已建立的 3D 细胞培养标准进行验证，以实现改善的治疗效果。
