RGDSP functionalized carboxylated agarose as extrudable carriers for chondrocyte delivery
RGDSP functionalized carboxylated agarose as extrudable carriers for chondrocyte delivery
复制标题
RGDSP功能化羧化琼脂糖作为软骨细胞递送的可挤压载体
DOI：
10.1016/j.msec.2019.01.080
复制
发表时间：
2019-06-01
影响因子：
7.9
通讯作者：
Shastri, V. Prasad
中科院分区：
文献类型：
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作者：
Arya, Neha;Forget, Aurelien;Shastri, V. Prasad
软骨自身再生的有限潜力导致了用于软骨组织工程和再生医学的新策略和生物材料的开发。尽管已经实现了软骨修复的从头策略，但可以以微创方式施用同时支持软骨分化的可挤出水凝胶可能导致开发新系统以将细胞递送至软骨病变。在这项工作中，我们探讨了热可逆的，可挤出的凝胶衍生自羧化琼脂糖维持人类关节软骨细胞（HAC）表型的适用性。为此，我们研究了水凝胶硬度和整合素结合肽序列GGGGRGDSP的存在对HAC分化潜力的影响。我们发现较硬的水凝胶（5.8kPa）在促进软骨形成方面比较软的对应物（0.6kPa）更有效。有趣的是，在GGGGRGDSP修饰的凝胶中，刚度和RGD信号传导之间的协同作用导致软骨形成相关基因（聚集蛋白聚糖、II型胶原蛋白和sox 9）的表达增强。这些发现也得到了硫酸化糖胺聚糖定量分析的支持。由于羧化琼脂糖非常适合作为3D生物打印的生物墨水，因此我们提出可挤出的GGGGRGDSP连接的刚性羧化琼脂糖作为将软骨细胞直接打印到软骨病变中的介质。
The limited potential of cartilage to regenerate itself has led to development of new strategies and biomaterials for cartilage tissue engineering and regenerative medicine. Although de novo strategies for cartilage repair have been realized, extrudable hydrogels that can be administered in minimally invasive manner while simultaneously supporting chondrogenic differentiation could lead to development of new systems to deliver cells to cartilage lesions. In this work, we explored the suitability of thermo-reversible, extrudable gels derived from carboxylated agarose for maintaining human articular chondrocyte (HAC) phenotype. Towards this objective, we have investigated the impact of hydrogel stiffness and presence of integrin-binding peptide sequence GGGGRGDSP on HAC differentiation potential. We discovered that stiffer hydrogels (5.8 kPa) are more efficient than softer counterparts (0.6 kPa) in promoting chondrogenesis. Interestingly, in GGGGRGDSP modified gels, a synergy between stiffness and RGD signaling led to enhanced expression of chondrogenic related genes (aggrecan, collagen type II and sox9). These findings were also supported by quantitative analysis of sulfated glycosaminoglycans. Since carboxylated agarose are highly suitable as bioink for 3D bioprinting, we propose that extrudable GGGGRGDSP-linked stiff carboxylated agarose as a medium for direct printing of chondrocyte into cartilage lesion.