Yang Qianhao, Xu Mengqiao, Fang Haoyu, Gao Youshui, Zhu Daoyu, Wang Jing, Chen Yixuan
Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Eye Institute and Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai, 200031, China.
Bioact Mater. 2024 May 16;39:41-58. doi: 10.1016/j.bioactmat.2024.05.023. eCollection 2024 Sep.
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 NbC nanosheets into a thermally responsive poly(N-isopropylacrylamide) (NIPAM) hydrogel system. NIR-II-triggered deformation of the NIPAM/NbC 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 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/NbC 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.
当施加精确调节的机械力和适当的微动时，自然骨折愈合效率最高。为了在骨折间隙模拟这种微动，通过将二维（2D）单层NbC纳米片整合到热响应性聚（N-异丙基丙烯酰胺）（NIPAM）水凝胶系统中，制备了一种近红外-II（NIR-II）激活的水凝胶。NIPAM/NbC水凝胶的NIR-II触发变形旨在为共培养细胞产生精确的微动。经证实，1/300 Hz的微动触发细胞长度/直径比变化2.37倍，是骨髓间充质干细胞（BMSC）成骨分化的最有利条件。此外，mRNA测序和验证表明，微动诱导的增强是由Piezo1激活介导的。抑制Piezo1会中断机械敏感性并消除成骨分化。建立了颅骨和股骨干缺损模型，以探索微动生物材料的生物相容性和骨诱导性。已经进行了一系列研究方法，包括放射照相、显微CT扫描和免疫组织化学染色，以评估生物安全性和成骨效果。结果表明，可调微动通过软骨内骨化的顺序激活、促进新血管形成、启动矿物质沉积和联合加速全层骨再生来加强自然骨折愈合过程。这项研究表明，具有可控机械物理特性的微动生物材料可以促进BMSC的成骨分化并促进全骨再生。具有高效光热转换、精确控制微动的特定特征和仿生骨修复能力的NIPAM/NbC水凝胶设计可能会开创再生医学领域的新纪元。
