Zheng Zheng, Gan Shuaiqi, Yang Shuhan, Hou Chuping, Zhu Zhimin, Wang Hang, Yu Deping, Qian Zhiyong, Xu Hockin H K, Chen Wenchuan
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
School of Mechanical Engineering, Sichuan University, Chengdu 610041, China.
J Mater Chem B. 2025 Jan 2;13(2):496-510. doi: 10.1039/d4tb02360a.
Titanium (Ti) implants have become widespread especially in dentistry and orthopedics, where macrophage-driven osteoimmunomodulation is crucial to their success. Hydrophilic modification of Ti represents a promising strategy to enhance its immune and osteogenic responses. Herein, the osteoimmunomodulatory performance and integrin-mediated mechanism of novel non-thermal atmospheric plasma (NTAP) treatment to induce a hydrophilic Ti were investigated for the first time. Compared to a hydrophobic surface, NTAP-modified Ti possessed a 3-fold increase of pro-healing M2 macrophage makers, and the doubled osteogenic differentiation of mesenchymal stem cells was demonstrated in this immune microenvironment, thus improving early osseointegration. Mechanistically, the ameliorative osteoimmunomodulatory properties of NTAP were attributed to its positive and negative modulation in macrophages' integrin β1 or β2, and the subsequent FAK-PI3K/Akt or NF-κB signaling pathway. Collectively, this study highlighted the role of integrins and related signaling pathways in hydrophilic implant-caused macrophage polarization, therefore inventively unveiling the underlying mechanism of NTAP-enhanced osteoimmunomodulation. Furthermore, it established a robust theoretical foundation for the clinical application of this cost-effective, versatile, and transformation-valuable surface engineering strategy for the development of next-generation Ti implants.
钛（Ti）植入物已广泛应用，尤其是在牙科和骨科领域，其中巨噬细胞驱动的骨免疫调节对其成功至关重要。钛的亲水性修饰是增强其免疫和骨生成反应的一种有前景的策略。在此，首次研究了新型非热大气等离子体（NTAP）处理诱导亲水性钛的骨免疫调节性能和整合素介导的机制。与疏水表面相比，NTAP修饰的钛使促愈合M2巨噬细胞标志物增加了3倍，并且在这种免疫微环境中，间充质干细胞的成骨分化增加了一倍，从而改善了早期骨整合。从机制上讲，NTAP改善的骨免疫调节特性归因于其对巨噬细胞整合素β1或β2的正负调节，以及随后的FAK-PI3K/Akt或NF-κB信号通路。总体而言，本研究突出了整合素和相关信号通路在亲水性植入物引起的巨噬细胞极化中的作用，因此创造性地揭示了NTAP增强骨免疫调节的潜在机制。此外，它为这种具有成本效益、多功能且具有转化价值的表面工程策略在下一代钛植入物开发中的临床应用奠定了坚实的理论基础。
