UCIBIO, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus Caparica, 2829-516 Caparica, Portugal.
Department of Bioengineering, iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 049-001 Lisboa, Portugal.
Biomacromolecules. 2020 Aug 10;21(8):3081-3091. doi: 10.1021/acs.biomac.0c00473. Epub 2020 Jul 7.
Tissue engineering and stem cell research greatly benefit from cell encapsulation within hydrogels as it promotes cell expansion and differentiation. Affinity-triggered hydrogels, an appealing solution for mild cell encapsulation, rely on selective interactions between the ligand and target and also on the multivalent presentation of these two components. Although these hydrogels represent a versatile option to generate dynamic, tunable, and highly functional materials, the design of hydrogel properties based on affinity and multivalency remains challenging and unstudied. Here, the avidin-biotin affinity pair, with the highest reported affinity constant, is used to address this challenge. It is demonstrated that the binding between the affinity hydrogel components is influenced by the multivalent display selected. In addition, the natural multivalency of the interaction must be obeyed to yield robust multicomponent synthetic protein hydrogels. The hydrogel's resistance to erosion depends on the right stoichiometric match between the hydrogel components. The developed affinity-triggered hydrogels are biocompatible and support encapsulation of induced pluripotent stem cells and their successful differentiation into a neural cell line. This principle can be generalized to other affinity pairs using multimeric proteins, yielding biomaterials with controlled performance.
组织工程和干细胞研究从水凝胶内细胞包封中受益匪浅，因为它促进了细胞的扩增和分化。亲和触发水凝胶作为温和细胞包封的一种有吸引力的解决方案，依赖于配体和靶标之间的选择性相互作用，以及这两个组件的多价呈现。尽管这些水凝胶代表了一种生成动态、可调谐和高功能材料的多功能选择，但基于亲和性和多价性的水凝胶特性的设计仍然具有挑战性和未被研究。在这里，使用具有最高报道亲和力常数的亲和素-生物素亲和对来解决这一挑战。结果表明，亲和水凝胶组件之间的结合受到所选择的多价显示的影响。此外，为了产生稳健的多组分合成蛋白水凝胶，必须遵守相互作用的天然多价性。水凝胶的抗侵蚀能力取决于水凝胶成分之间的正确化学计量匹配。所开发的亲和触发水凝胶具有生物相容性，并支持诱导多能干细胞的封装及其成功分化为神经细胞系。这一原理可以使用多聚体蛋白推广到其他亲和对，从而产生具有可控性能的生物材料。
