A transient cell-shielding method for viable MSC delivery within hydrophobic scaffolds polymerized in situ.
A transient cell-shielding method for viable MSC delivery within hydrophobic scaffolds polymerized in situ.
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DOI：
10.1016/j.biomaterials.2015.03.010
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发表时间：
2015-06
期刊：
影响因子：
14
通讯作者：
Guelcher SA
中科院分区：
文献类型：
--
作者：
Guo R;Ward CL;Davidson JM;Duvall CL;Wenke JC;Guelcher SA
基于细胞的疗法已经成为再生医学的有前途的方法。疏水性聚(酯)氨酯S具有良好的力学性能，无需使用多肽就能附着细胞，并可通过氧化和水解机制控制降解。然而，可注射疏水聚合物在细胞输送中的应用受到保护细胞免受反应产物的影响和在固化后创建大孔结构的挑战的限制。我们设计了用于细胞输送的可注射载体，这些载体来自反应性、疏水性多异氰酸酯和聚酯三醇前体。为了克服原位聚合反应产物引起的细胞死亡，我们将骨髓来源的干细胞(BMSCs)包裹在快速降解的氧化海藻酸盐珠中，然后与疏水前体混合。细胞在70%的聚合率下存活下来，在支架固化后，氧化的海藻酸盐珠迅速溶解，产生相互连接的大孔，促进细胞在体外与支架的粘连。应用这种可注射系统将BMSCs输送到大鼠切除的皮肤伤口上，结果表明，这种支架支持了移植细胞的存活和宿主细胞的渗透，与植入的、预形成的、种植了细胞的支架和无细胞对照相比，这促进了新组织的形成。我们的设计首次实现了可注射的可固定疏水支架的输送，其中细胞封装为聚合过程中的临时细胞保护和聚合后大孔的快速形成提供了一种机制。与水凝胶技术相比，这种简单的方法为细胞输送提供了潜在的优势，水凝胶技术的机械性能较弱，需要掺入多肽来实现细胞黏附和降解。
Cell-based therapies have emerged as promising approaches for regenerative medicine. Hydrophobic poly(ester urethane)s offer the advantages of robust mechanical properties, cell attachment without the use of peptides, and controlled degradation by oxidative and hydrolytic mechanisms. However, the application of injectable hydrophobic polymers to cell delivery is limited by the challenges of protecting cells from reaction products and creating a macroporous architecture post-cure. We designed injectable carriers for cell delivery derived from reactive, hydrophobic polyisocyanate and polyester triol precursors. To overcome cell death caused by reaction products from in situ polymerization, we encapsulated bone marrow-derived stem cells (BMSCs) in fast-degrading, oxidized alginate beads prior to mixing with the hydrophobic precursors. Cells survived the polymerization at >70% viability, and rapid dissolution of oxidized alginate beads after the scaffold cured created interconnected macropores that facilitated cellular adhesion to the scaffold in vitro. Applying this injectable system to deliver BMSCs to rat excisional skin wounds showed that the scaffolds supported survival of transplanted cells and infiltration of host cells, which improved new tissue formation compared to both implanted, pre-formed scaffolds seeded with cells and acellular controls. Our design is the first to enable injectable delivery of settable, hydrophobic scaffolds where cell encapsulation provides a mechanism for both temporary cytoprotection during polymerization and rapid formation of macropores post-polymerization. This simple approach provides potential advantages for cell delivery relative to hydrogel technologies, which have weaker mechanical properties and require incorporation of peptides to achieve cell adhesion and degradability.
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影响因子：
4.9
作者：
Adolph, Elizabeth J.;Hafeman, Andrea E.;Davidson, Jeffrey M.;Nanney, Lillian B.;Guelcher, Scott A.
通讯作者：
Guelcher, Scott A.
影响因子：
4.1
作者：
Chen, Wenchuan;Zhou, Hongzhi;Xu, Hockin H. K.
通讯作者：
Xu, Hockin H. K.
影响因子：
9
作者：
Hwang CM;Sant S;Masaeli M;Kachouie NN;Zamanian B;Lee SH;Khademhosseini A
通讯作者：
Khademhosseini A
影响因子：
2.8
作者：
Dennis, JE;Cohen, N;Caplan, AI
通讯作者：
Caplan, AI
影响因子：
9.7
作者：
Balakrishnan, Biji;Joshi, Nitin;Banerjee, Rinti
通讯作者：
Banerjee, Rinti