Development and optimization of a dual-photoinitiator, emulsion-based technique for rapid generation of cell-laden hydrogel microspheres
Development and optimization of a dual-photoinitiator, emulsion-based technique for rapid generation of cell-laden hydrogel microspheres
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DOI：
10.1016/j.actbio.2011.06.011
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发表时间：
2011-09-01
影响因子：
9.7
通讯作者：
West, J. L.
中科院分区：
文献类型：
--
作者：
Franco, C. L.;Price, J.;West, J. L.
越来越多的临床试验探索使用基于细胞的疗法治疗疾病和修复受损组织;然而，有限的细胞存活和植入仍然是一个重大挑战。随着该领域的不断发展，微囊化策略被证明是保护和支持这些细胞疗法的有价值的工具，同时保持微创递送。这项工作提出了一种新的，双光引发剂的水凝胶微球内的细胞封装技术。使用台式涡旋器来产生聚（乙二醇）二丙烯酸酯（PEGDA）或基于PEGDA的前体溶液在矿物油中的乳液。通过将光引发剂的优化组合添加到水相和油相中，实现了悬浮聚合物液滴的快速凝胶化。光引发剂组合提供了上级交联一致性和更大的颗粒产率，并且与单一引发剂体系相比需要更低的总引发剂浓度。当细胞与前体溶液组合时，这些益处转化为优异的微囊化产率，对于测试的细胞类型具有60-80%的活力。进一步表明，支架材料可以用细胞粘附肽修饰以用作表面接种的微载体，或者另外用酶促可降解序列修饰以支持包封细胞的三维铺展、迁移和长期培养。这里展示了与神经干细胞疗法相关的三种细胞系，但这项技术具有适应性，可扩展性，易于使用标准实验室设备实施，使其成为推进下一代细胞疗法的有用工具。(C)2011由Elsevier Ltd.代表Acta Materialia Inc.出版。
A growing number of clinical trials explore the use of cell-based therapies for the treatment of disease and restoration of damaged tissue; however, limited cell survival and engraftment remains a significant challenge. As the field continues to progress, microencapsulation strategies are proving to be a valuable tool for protecting and supporting these cell therapies while preserving minimally invasive delivery. This work presents a novel, dual-photoinitiator technique for encapsulation of cells within hydrogel microspheres. A desktop vortexer was used to generate an emulsion of poly(ethylene glycol) diacrylate (PEGDA) or PEGDA-based precursor solution in mineral oil. Through an optimized combination of photoinitiators added to both the aqueous and the oil phase, rapid gelation of the suspended polymer droplets was achieved. The photoinitiator combination provided superior cross-linking consistency and greater particle yield, and required lower overall initiator concentrations compared with a single initiator system. When cells were combined with the precursor solution, these benefits translated to excellent microencapsulation yield with 60-80% viability for the tested cell types. It was further shown that the scaffold material could be modified with cell-adhesive peptides to be used as surface-seeded microcarriers, or additionally with enzymatically degradable sequences to support three-dimensional spreading, migration and long-term culture of encapsulated cells. Three cell lines relevant to neural stem cell therapies are demonstrated here, but this technology is adaptable, scalable and easy to implement with standard laboratory equipment, making it a useful tool for advancing the next generation of cell-based therapeutics. (C) 2011 Published by Elsevier Ltd. on behalf of Acta Materialia Inc.