Targeting micromotion for mimicking natural bone healing by using NIPAM/Nb<sub>2</sub>C hydrogel.

Yang, Qianhao; Xu, Mengqiao; Fang, Haoyu; Gao, Youshui; Zhu, Daoyu; Wang, Jing; Chen, Yixuan · Bioact Mater · 2024

basic_science · Level V

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Abstract

Natural fracture healing is most efficient when the fine-tuned mechanical force and proper micromotion are applied. To mimick this micromotion at the fracture gap, a near-infrared-II (NIR-II)-activated hydrogel was fabricated by integrating two-dimensional (2D) monolayer Nb<sub>2</sub>C nanosheets into a thermally responsive poly(N-isopropylacrylamide) (NIPAM) hydrogel system. NIR-II-triggered deformation of the NIPAM/Nb<sub>2</sub>C hydrogel was designed to generate precise micromotion for co-culturing cells. It was validated that micromotion at 1/300 Hz, triggering a 2.37-fold change in the cell length/diameter ratio, is the most favorable condition for the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Moreover, mRNA sequencing and verification revealed that micromotion-induced augmentation was mediated by Piezo1 activation. Suppression of Piezo1 interrupts the mechano-sensitivity and abrogates osteogenic differentiation. Calvarial and femoral shaft defect models were established to explore the biocompatibility and osteoinductivity of the Micromotion Biomaterial. A series of research methods, including radiography, micro-CT scanning, and immunohistochemical staining have been performed to evaluate biosafety and osteogenic efficacy. The <i>in vivo</i> results revealed that tunable micromotion strengthens the natural fracture healing process through the sequential activation of endochondral ossification, promotion of neovascularization, initiation of mineral deposition, and combinatory acceleration of full-thickness osseous regeneration. This study demonstrated that Micromotion Biomaterials with controllable mechanophysical characteristics could promote the osteogenic differentiation of BMSCs and facilitate full osseous regeneration. The design of NIPAM/Nb<sub>2</sub>C hydrogel with highly efficient photothermal conversion, specific features of precisely controlled micromotion, and bionic-mimicking bone-repair capabilities could spark a new era in the field of regenerative medicine.