Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510055, China.
School of Materials Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, Guangdong, 510641, China.
J Nanobiotechnology. 2024 Feb 7;22(1):54. doi: 10.1186/s12951-024-02320-y.
The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects.
用具有适应性的骨植入物来治疗具有不规则形状的临界尺寸骨缺损仍然是骨科领域的一个主要挑战。这种骨植入物需要具有适应复杂形态骨缺损的能力、骨黏附特性和强大的成骨能力。在这里，通过动态共价交联胺修饰的压电纳米粒子和生物聚合物水凝胶网络，开发了一种形状适应性强、高度骨黏附且具有超声动力的可注射纳米复合水凝胶，用于电加速骨愈合。根据氨基修饰的压电纳米粒子与生物黏附水凝胶网络之间的无机-有机相互作用，制备的水凝胶的骨黏附强度增加了约 3 倍。响应超声辐射，纳米复合水凝胶可以产生可控的电输出（-41.16 至 61.82 mV），从而显著增强体外和体内的成骨效果。大鼠临界尺寸颅骨缺损修复验证了加速骨愈合。此外，生物信息学分析表明，超声响应纳米复合水凝胶通过增加钙离子内流和上调 PI3K/AKT 和 MEK/ERK 信号通路来增强骨髓间充质干细胞的成骨分化。总的来说，本工作揭示了一种新型的无线超声驱动的骨黏附纳米复合水凝胶，为不规则骨缺损的治疗开辟了新的途径。
