Targeting micromotion for mimicking natural bone healing by using NIPAM/Nb_(2)C hydrogel  

作　　者：Qianhao Yang Mengqiao Xu Haoyu Fang Youshui Gao Daoyu Zhu Jing Wang Yixuan Chen 

机构地区：[1]Department of Orthopedic Surgery,Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai,200233,China [2]Eye Institute and Department of Ophthalmology,Eye and ENT Hospital,Fudan University,Shanghai,200031,China

出　　处：《Bioactive Materials》2024年第9期41-58,共18页生物活性材料（英文）

基　　金：funded by the National Natural Science Foundation of China(Grant No.81902237,82072417,82302693);the Shanghai Sailing Program(Grant NO.21YF1433700,23YF1432400);the China Postdoctoral Science Foundation(Grant No.2023M742324).

摘　　要：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 Nb2C nanosheets into a thermally responsive poly(Nisopropylacrylamide)(NIPAM)hydrogel system.NIR–II–triggered deformation of the NIPAM/Nb2C 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 in vivo 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/Nb2C 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.

关 键 词：MICROMOTION BMSCS OSTEOGENESIS Mechanical force Regenerative medicine 

分 类 号：TQ427.26[化学工程] R318[医药卫生—生物医学工程]