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

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.

Automated summary

The study highlights the importance of TRPM8 in bone mineralization and how its inhibition can lead to upregulation of key osteogenesis factors and increased mineralization by osteoblasts. The use of CMT:HEMA hydrogel allows for effective delivery of TRPM8-specific activators or inhibitors, promoting adhesion, growth, and differentiation of osteoblasts and BM-MSCP. Coating CMT:HEMA with AMTB induces differentiation of BM-MSCP into osteoblasts in a dose-dependent manner, showcasing its potential in bone tissue engineering.