Oxidized alginate beads for tunable release of osteogenically potent mesenchymal stromal cells.
Oxidized alginate beads for tunable release of osteogenically potent mesenchymal stromal cells.
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DOI：
10.1016/j.msec.2019.109911
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发表时间：
2019-11
期刊：
影响因子：
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通讯作者：
Gao Xiang;E. Lippens;S. Hafeez;G. Duda;S. Geissler;T. Qazi
中科院分区：
文献类型：
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作者：
Gao Xiang;E. Lippens;S. Hafeez;G. Duda;S. Geissler;T. Qazi
骨缺损修复可以受益于间充质基质细胞（MSC）的局部递送。然而，受伤后当地恶劣的环境条件可能需要一种细胞治疗策略，首先保护间充质干细胞，然后随着时间的推移在局部释放它们。这可以通过使用具有刺激响应降解性的生物材料来实现，例如经历水解降解的氧化藻酸盐水凝胶。然而，不同的封装时间是否会影响释放后的 MSC 成骨分化能力仍不清楚。为了解决这个问题，我们在表征释放细胞的功能之前，在具有可调降解性的 3D 藻酸盐珠中培养 MSC。海藻酸盐被氧化到不同程度（2%、3% 和 4%），以实现不同的降解速度（数天到数周），然后用 RGD 肽进行功能化以实现细胞粘附，并用 6-氨基荧光素进行额外修饰以实现基于荧光的检测。随着时间的推移，监测珠形态、降解动力学、细胞形态和细胞释放动力学。从珠子中释放的细胞被刺激分化成成骨谱系。我们的结果表明，从所有珠组释放的 MSC 在成骨分化条件下保留了沉积矿化基质的强大能力。这些发现为设计和实施基于生物材料的策略提供了基础，以便在骨缺损部位原位临时输送有效的 MSC。
Bone defect repair can benefit from local delivery of mesenchymal stromal cells (MSCs). However, local harsh environmental conditions after injury may necessitate a cell therapy strategy that shields MSCs initially and releases them locally over time. This may be possible by using biomaterials that exhibit stimuli-responsive degradability, such as oxidized alginate hydrogels that undergo hydrolytic degradation. However, it remains unknown whether varying encapsulation periods compromise MSC osteogenic differentiation capacity after release. To address this, we cultured MSCs in 3D alginate beads with tunable degradability before characterizing the function of released cells. Alginates were oxidized to different degrees (2%, 3%, and 4%) to achieve distinct rates of degradation (days to weeks), then functionalized with RGD peptides to enable cell adhesion, and modified additionally with 6-aminofluorescin to enable fluorescence-based detection. Bead morphology, degradation kinetics, cell morphology, and cell release kinetics were monitored over time. Cells that were released from the beads were stimulated to differentiate into the osteogenic lineage. Our results indicate that MSCs released from all bead groups retained a strong ability to deposit mineralized matrix under osteogenic differentiation conditions. These findings provide the basis for designing and implementing biomaterial-based strategies for the in-situ temporal delivery of potent MSCs at bone defect sites.