Thermoresponsive Inverted Colloidal Crystal Hydrogel Scaffolds for Lymphoid Tissue Engineering
Thermoresponsive Inverted Colloidal Crystal Hydrogel Scaffolds for Lymphoid Tissue Engineering
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DOI：
10.1002/adhm.201901556
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发表时间：
2020-02-04
影响因子：
10
通讯作者：
Lee, Jungwoo
中科院分区：
文献类型：
--
作者：
Kwak, Jun-Goo;Lee, Jungwoo
倒置胶体晶体（ICC）水凝胶支架代表了建模淋巴组织和扩增造血淋巴细胞的独特机会。完全互连的球形孔阵列指导基质网络的形成，并促进基质和造血淋巴细胞之间的相互作用。然而，由于这些材料的复杂结构，扩增细胞的释放受到限制，并且需要水凝胶支架的机械破坏或化学溶解。一种有效的生物材料策略，释放孔截留的造血淋巴细胞，而不打破支架分开是暂时增加这些材料的尺寸使用刺激响应聚合物。有了这种思维方式，开发了通过使用具有纳米凝胶交联剂的聚（N-异丙基丙烯酰胺）（PNIPAM）在生理温度范围（4-37摄氏度）内经历快速（300%）直径变化的温敏ICC支架。对于概念验证研究，首先复制通过产生骨球、成骨细胞聚集体和骨碎片的基质小生境，随后引入Nalm-6模型造血淋巴细胞。当ICC水凝胶支架扩增而不终止所建立的3D基质细胞培养时，收获细胞计数增加六倍。设想温敏性ICC水凝胶支架将能够实现造血淋巴细胞的可扩展和可持续的离体扩增。
Inverted colloidal crystal (ICC) hydrogel scaffolds represent unique opportunities in modeling lymphoid tissues and expanding hematopoietic-lymphoid cells. Fully interconnected spherical pore arrays direct the formation of stromal networks and facilitate interactions between stroma and hematopoietic-lymphoid cells. However, due to the intricate architecture of these materials, release of expanded cells is restricted and requires mechanical disruption or chemical dissolution of the hydrogel scaffold. One potent biomaterials strategy to release pore-entrapped hematopoietic-lymphoid cells without breaking the scaffolds apart is to transiently increase the dimensions of these materials using stimuli-responsive polymers. Having this mindset, thermoresponsive ICC scaffolds that undergo rapid (300%) diameter change over a physiological temperature range (4-37 degrees C) by using poly(N-isopropylacrylamide) (PNIPAM) with nanogel crosslinkers is developed. For a proof-of-concept study, the stromal niche by creating osteospheroids, aggregates of osteoblasts, and bone chips is first replicated, and subsequently Nalm-6 model hematopoietic-lymphoid cells are introduced. A sixfold increase in cell count is harvested when ICC hydrogel scaffolds are expanded without termination of the established 3D stromal cell culture. It is envisioned that thermoresponsive ICC hydrogel scaffolds will enable for scalable and sustainable ex vivo expansion of hematopoietic-lymphoid cells.