Treating different types of bone defects is difficult, complicated, time-consuming, and expensive. Here, we demonstrate that transient receptor potential cation channel subfamily V member 4 (TRPV4), a mechanosensitive, thermogated, and nonselective cation channel, is endogenously present in the mesenchymal stem cells (MSCs). TRPV4 regulates both cytosolic Ca²⁺ levels and mitochondrial health. Accordingly, the hydrogel made from a natural modified biopolymer carboxymethyl tamarind CMT-Hy and encapsulated with TRPV4-modulatory agents affects different parameters of MSCs, such as cell morphology, focal adhesion points, intracellular Ca²⁺, and reactive oxygen species- and NO-levels. TRPV4 also regulates cell differentiation and biomineralization in vitro. We demonstrate that 4α-10-CMT-Hy and 4α-50-CMT-Hy (the hydrogel encapsulated with 4αPDD, 10 and 50 nM, TRPV4 activator) surfaces upregulate mitochondrial health, i.e., an increase in ATP- and cardiolipin-levels, and improve the mitochondrial membrane potential. The same scaffold turned out to be nontoxic in vivo. 4α-50-CMT-Hy enhances the repair of the bone-drill hole in rat femur, both qualitatively and quantitatively in vivo. We conclude that 4α-50-CMT-Hy as a scaffold is suitable for treating large-scale bone defects at low cost and can be tested for clinical trials.

中文翻译：

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含有 TRPV4 激活剂的 CMT-Hy 水凝胶通过增强线粒体健康来增强体内骨组织再生

治疗不同类型的骨缺损是困难、复杂、耗时且昂贵的。在这里，我们证明瞬时受体电位阳离子通道亚家族 V 成员 4 (TRPV4) 是一种机械敏感、热控和非选择性的阳离子通道，内源性存在于间充质干细胞 (MSC) 中。 TRPV4 调节胞质 Ca ²⁺水平和线粒体健康。因此，由天然改性生物聚合物羧甲基罗望子 CMT-Hy 制成并用 TRPV4 调节剂封装的水凝胶会影响 MSC 的不同参数，例如细胞形态、粘着斑、细胞内 Ca ²⁺以及活性氧和 NO-水平。 TRPV4 还在体外调节细胞分化和生物矿化。我们证明 4α-10-CMT-Hy 和 4α-50-CMT-Hy（封装有 4αPDD、10 和 50 nM、TRPV4 激活剂的水凝胶）表面上调线粒体健康，即 ATP 和心磷脂水平增加，并提高线粒体膜电位。事实证明，相同的支架在体内是无毒的。 4α-50-CMT-Hy在体内定性和定量地增强大鼠股骨骨钻孔的修复。我们的结论是，4α-50-CMT-Hy 作为支架适合以低成本治疗大面积骨缺损，并且可以进行临床试验。