School of Biological Sciences, National Institute of Science Education and Research (NISER)-Bhubaneswar, Jatni, Khurda, 752050, Odisha, India.
Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400094, India.
Sci Rep. 2021 Feb 12;11(1):3730. doi: 10.1038/s41598-021-81041-w.
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 Ca-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.
生物医学领域的一个主要限制是缺乏适合使用干细胞进行骨组织工程的材料，以及将随机生物事件转化为明确和高效的生物矿化的方法。我们表明成骨细胞和骨髓间充质干细胞池（BM-MSCP）表达 TRPM8，这是一种对于骨矿化至关重要的 Ca2+离子通道。TRPM8 抑制会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，这是一种基于碳水化合物聚合物的水凝胶，具有纳米纤维样结构，适合最佳递呈 TRPM8 特异性激活剂或抑制剂。这种水凝胶非常适合成骨细胞系、原代成骨细胞和 BM-MSCP 的适当粘附、生长和分化。用 AMTB（TRPM8 抑制剂）涂覆的 CMT:HEMA 以剂量依赖的方式诱导 BM-MSCP 分化为成骨细胞，随后矿化。从凝胶中释放的 AMTB 对 TRPM8 的长期和最佳抑制导致成骨标志物的上调。我们提出，AMTB 涂覆的 CMT:HEMA 可用作骨组织工程的可调谐表面。这些发现可能在不同的生物医学领域具有广泛的意义。
