Chen Qiushui, Chen Dong, Wu Jing, Lin Jin-Ming
Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Tsinghua University , Beijing, China.
Institute of Process Equipment, College of Chemical and Biological Engineering, Zhejiang University , Hangzhou, China.
Biomicrofluidics. 2016 Dec 8;10(6):064115. doi: 10.1063/1.4972107. eCollection 2016 Nov.
Designing cell-compatible, bio-degradable, and stimuli-responsive hydrogels is very important for biomedical applications in cellular delivery and micro-scale tissue engineering. Here, we report achieving flexible control of cellular microencapsulation, permeability, and release by rationally designing a diblock copolymer, alginate-conjugated poly(N-isopropylacrylamide) (Alg-co-PNiPAM). We use the microfluidic technique to fabricate the bifunctional copolymers into thousands of mono-disperse droplet-templated hydrogel microparticles for controlled encapsulation and triggered release of mammalian cells. In particular, the grafting PNiPAM groups in the synthetic cell-laden microgels produce lots of nano-aggregates into hydrogel networks at elevated temperature, thereafter enhancing the permeability of microparticle scaffolds. Importantly, the hydrogel scaffolds are readily fabricated via on-chip quick gelation by triggered release of Ca from the Ca-EDTA complex; it is also quite exciting that very mild release of microencapsulated cells is achieved via controlled degradation of hydrogel scaffolds through a simple strategy of competitive affinity of Ca from the Ca-Alginate complex. This finding suggests that we are able to control cellular encapsulation and release through ion-induced gelation and degradation of the hydrogel scaffolds. Subsequently, we demonstrate a high viability of microencapsulated cells in the microgel scaffolds.
设计具有细胞相容性、生物可降解性和刺激响应性的水凝胶对于细胞递送和微尺度组织工程中的生物医学应用非常重要。在此，我们报告通过合理设计一种二嵌段共聚物，即藻酸盐共轭聚（N-异丙基丙烯酰胺）（Alg-co-PNiPAM），实现对细胞微囊化、渗透性和释放的灵活控制。我们使用微流控技术将双功能共聚物制备成数千个单分散的液滴模板水凝胶微粒，用于对哺乳动物细胞进行可控封装和触发释放。特别是，在合成的载有细胞的微凝胶中接枝的PNiPAM基团在高温下会在水凝胶网络中产生大量纳米聚集体，从而提高微粒支架的渗透性。重要的是，水凝胶支架可通过从Ca-EDTA络合物中触发释放Ca来实现片上快速凝胶化而轻松制备；同样令人兴奋的是，通过一种简单的策略，即利用Ca-藻酸盐络合物中Ca的竞争亲和力来控制水凝胶支架的降解，从而实现微囊化细胞的非常温和的释放。这一发现表明，我们能够通过离子诱导的水凝胶支架凝胶化和降解来控制细胞的封装和释放。随后，我们证明了微凝胶支架中微囊化细胞具有高活力。
