Xian Ruoting, Xian Hongyi, Dong Hao, Lin Jiating, Zhuang Xianxian, Zou Yue, Xie Qinkai, Liang Youde, Li Shaobing
Center of Oral Implantology, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou 510280, China.
National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou 510515, China.
ACS Appl Mater Interfaces. 2025 May 7;17(18):26371-26385. doi: 10.1021/acsami.5c02054. Epub 2025 Apr 24.
Repair and regeneration of oral and maxillofacial tissue defects remain significant challenges, mainly due to the limitations of existing treatment approaches. Conventional methods such as transplantation, tissue scaffolds, growth factors, and stem cell therapies often face obstacles, including donor shortages, insufficient vascularization, and safety concerns. There is an urgent need for innovative therapeutic strategies to effectively promote vascular regeneration while minimizing complications. Black phosphorus nanosheets (BPNSs) and hydrogels present significant advantages and broad application potential as tissue regeneration carriers due to their biocompatibility, degradability, and controlled drug release properties. By combining various characterization techniques and detection methods, we conducted a thorough analysis of BPNSs and gelatin methacryloyl (GelMA) scaffolds loaded with BPNSs (BP-GelMA). The results indicate that this study successfully prepared BPNSs with uniform size, good dispersion, and intact structure. Moreover, the BP-GelMA composite demonstrated excellent swelling behavior and structural stability while effectively enabling the controlled release of BPNSs. This study investigated the angiogenic effects of BP-GelMA at concentrations of 0, 12.5, and 25.0 μg/mL. experiments showed that BP-GelMA significantly enhanced endothelial cell proliferation, migration, and tube formation. results demonstrated that 12.5 μg/mL and 25.0 μg/mL BP-GelMA did not induce significant developmental toxicity in zebrafish and effectively promoted neovascularization. RNA-Seq analysis revealed that BP-GelMA activates angiogenesis-related biological processes. Mechanistic studies identified PEAK1 as a central regulator, driving vascular formation through activation of the MAPK signaling pathway. These findings highlight the potential of BP-GelMA as a therapeutic strategy for promoting angiogenesis and underscore the importance of optimizing BP-GelMA concentrations to achieve maximum therapeutic efficacy and safety in clinical applications.
口腔颌面部组织缺损的修复和再生仍然是重大挑战，主要是由于现有治疗方法的局限性。传统方法如移植、组织支架、生长因子和干细胞疗法常常面临障碍，包括供体短缺、血管化不足以及安全性问题。迫切需要创新的治疗策略来有效促进血管再生，同时将并发症降至最低。黑磷纳米片（BPNSs）和水凝胶由于其生物相容性、可降解性和可控药物释放特性，作为组织再生载体具有显著优势和广泛应用潜力。通过结合各种表征技术和检测方法，我们对BPNSs和负载BPNSs的明胶甲基丙烯酰（GelMA）支架（BP-GelMA）进行了全面分析。结果表明，本研究成功制备了尺寸均匀、分散良好且结构完整的BPNSs。此外，BP-GelMA复合材料表现出优异的溶胀行为和结构稳定性，同时有效地实现了BPNSs的可控释放。本研究考察了浓度为0、12.5和25.0μg/mL的BP-GelMA的促血管生成作用。实验表明，BP-GelMA显著增强了内皮细胞的增殖、迁移和管腔形成。结果表明，12.5μg/mL和25.0μg/mL的BP-GelMA在斑马鱼中未诱导明显的发育毒性，并有效促进了新血管形成。RNA测序分析表明，BP-GelMA激活了与血管生成相关的生物学过程。机制研究确定PEAK1为核心调节因子，通过激活MAPK信号通路驱动血管形成。这些发现突出了BP-GelMA作为促进血管生成治疗策略的潜力，并强调了优化BP-GelMA浓度以在临床应用中实现最大治疗效果和安全性的重要性。
