TRPM8 channel inhibitor-encapsulated hydrogel as a tunable surface for bone tissue engineering.

TRPM8 channel inhibitor-encapsulated hydrogel as a tunable surface for bone tissue engineering.
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DOI:
10.1038/s41598-021-81041-w
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发表时间:
2021-02-12
期刊:
影响因子:
4.6
通讯作者:
Goswami C
Goswami C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Acharya TK;Kumar S;Tiwari N;Ghosh A;Tiwari A;Pal S;Majhi RK;Kumar A;Das R;Singh A;Maji PK;Chattopadhyay N;Goswami L;Goswami C

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生物医学领域的一个主要限制是适用于使用干细胞的骨组织工程的材料的可用性,以及将随机生物事件转化为确定的以及有效的生物矿化的方法。我们发现成骨细胞和骨髓间充质干细胞(BM-MSCP)表达TRPM 8,这是一种对骨矿化至关重要的钙离子通道。TRPM 8抑制触发关键成骨因子的上调;并增加成骨细胞的矿化。我们利用CMT:HEMA,一种基于碳水化合物聚合物的水凝胶,其具有纳米纤维样结构,适合于TRPM 8特异性激活剂或抑制剂的最佳递送。这种水凝胶对于成骨细胞系、原代成骨细胞和BM-MSCP的适当粘附、生长和分化是理想的。CMT:涂有AMTB(TRPM 8抑制剂)的HEMA以剂量依赖性方式诱导BM-MSCP分化为成骨细胞和随后的矿化。从凝胶中释放的AMTB对TRPM 8的延长和最佳抑制导致成骨标志物的上调。我们建议AMTB涂层CMT:HEMA可用作骨组织工程的可调表面。这些发现可能对不同的生物医学领域产生广泛的影响。
A major limitation in the bio-medical sector is the availability of materials suitable for bone tissue engineering using stem cells and methodology converting the stochastic biological events towards definitive as well as efficient bio-mineralization. We show that osteoblasts and Bone Marrow-derived Mesenchymal Stem Cell Pools (BM-MSCP) express TRPM8, a Ca2+-ion channel critical for bone-mineralization. TRPM8 inhibition triggers up-regulation of key osteogenesis factors; and increases mineralization by osteoblasts. We utilized CMT:HEMA, a carbohydrate polymer-based hydrogel that has nanofiber-like structure suitable for optimum delivery of TRPM8-specific activators or inhibitors. This hydrogel is ideal for proper adhesion, growth, and differentiation of osteoblast cell lines, primary osteoblasts, and BM-MSCP. CMT:HEMA coated with AMTB (TRPM8 inhibitor) induces differentiation of BM-MSCP into osteoblasts and subsequent mineralization in a dose-dependent manner. Prolonged and optimum inhibition of TRPM8 by AMTB released from the gels results in upregulation of osteogenic markers. We propose that AMTB-coated CMT:HEMA can be used as a tunable surface for bone tissue engineering. These findings may have broad implications in different bio-medical sectors.
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