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Thermoresponsive Inverted Colloidal Crystal Hydrogel Scaffolds for Lymphoid Tissue Engineering.
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-02-04 , DOI: 10.1002/adhm.201901556
Jun-Goo Kwak 1 , Jungwoo Lee 2
Affiliation  

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 (<1 min) and substantial (>300%) diameter change over a physiological temperature range (4-37 °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.

中文翻译:

用于淋巴组织工程的热响应倒置胶体晶体水凝胶支架。

倒置胶体晶体(ICC)水凝胶支架代表了淋巴组织建模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,并且需要对水凝胶支架进行机械破坏或化学溶解。在不破坏支架的情况下释放孔内捕获的造血淋巴细胞的一种有效的生物材料策略是使用刺激响应聚合物暂时增加这些材料的尺寸。抱着这种心态,通过使用聚(N-异丙基丙烯酰胺)(PNIPAM)和纳米凝胶交联剂,热响应 ICC 支架在生理温度范围(4-37 °C)内经历快速(<1 分钟)和显着(>300%)的直径变化已开发。对于概念验证研究,首先通过创建骨球、成骨细胞聚集体和骨碎片来复制基质生态位,随后引入 Nalm-6 模型造血淋巴细胞。当 ICC 水凝胶支架在不终止已建立的 3D 基质细胞培养的情况下扩展时,细胞计数会增加六倍。预计热响应 ICC 水凝胶支架将能够实现造血淋巴细胞的可扩展且可持续的离体扩增。
更新日期:2020-03-19
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