Lin Mingyue, Stehle Yijing, Chen Li, Yang Mao, Zeng Ke, Wang Chenxin, Zhang Rui, Zhang Huanshuo, Yang Jiehui, Hu Denglang, Huang Min, Li Yubao, Zou Qin
Analytical & Testing Center, Sichuan University, Chengdu 610064, PR China.
Department of Mechanical Engineering, Union College, 807 Union St., Schenectady, NY 12308, USA.
Carbohydr Polym. 2025 Oct 15;366:123866. doi: 10.1016/j.carbpol.2025.123866. Epub 2025 Jun 6.
Despite advances in osteomyelitis treatment, achieving spatiotemporal coordination of infection control and bone regeneration remains challenging due to bacterial-induced acidic microenvironments and toxin-mediated osteoblast dysfunction. Herein, a novel 3D-printed chitosan-based composite scaffold (VM@n-HA/CS/DM) was developed. The scaffold strategically integrates two functional components: (1) Vancomycin-loaded chitosan microspheres (VM) conjugated with scaffold via pH-sensitive Schiff base bonds formed between aldehyde and amine groups, selectively breaking down in the acidic microenvironment of bacterial infections, thereby enabling on-demand release of vancomycin (Van) to target and eliminate Staphylococcus aureus (S. aureus). (2) Diflunisal-loaded chitosan microspheres (DM) dispersed within the scaffold matrix, providing sustained release to suppress alpha-type phenol-soluble modulins (PSMs) expression and shield osteoblasts from bacterial toxins. The scaffold employs pH-responsive and diffusion-mediated mechanisms to match the timing of infection control and bone regeneration. Furthermore, the 3D-printed hierarchical porous structure, with spatially optimized microsphere/matrix distribution, ensures dual functionality: multiscale porosity facilitates nutrient transport and cell infiltration while maintaining mechanical integrity, and compartmentalized drug delivery achieves precise therapeutic control. This dual therapeutic modality advances osteomyelitis treatment by providing a clinically viable strategy to address persistent challenges.
尽管骨髓炎治疗取得了进展，但由于细菌诱导的酸性微环境和毒素介导的成骨细胞功能障碍，实现感染控制和骨再生的时空协调仍然具有挑战性。在此，开发了一种新型的3D打印壳聚糖基复合支架（VM@n-HA/CS/DM）。该支架策略性地整合了两个功能组件：（1）负载万古霉素的壳聚糖微球（VM）通过醛基和胺基之间形成的pH敏感席夫碱键与支架共轭，在细菌感染的酸性微环境中选择性分解，从而实现万古霉素（Van）的按需释放，以靶向并消除金黄色葡萄球菌（S. aureus）。（2）负载双氯芬酸的壳聚糖微球（DM）分散在支架基质中，提供持续释放以抑制α型酚溶性调节素（PSMs）的表达，并保护成骨细胞免受细菌毒素的影响。该支架采用pH响应和扩散介导机制来匹配感染控制和骨再生的时机。此外，3D打印的分级多孔结构具有空间优化的微球/基质分布，确保了双重功能：多尺度孔隙率促进营养物质运输和细胞浸润，同时保持机械完整性，而分区药物递送实现了精确的治疗控制。这种双重治疗方式通过提供一种临床上可行的策略来应对持续存在的挑战，推动了骨髓炎的治疗。
