已传文件：photo/1770081635.png
To address the core challenge of simultaneously controlling infection and promoting bone regeneration in cases of bone defects, as well as the inhibitory effect of excessive sympathetic nerve activation on the repair process, this study developed a multifunctional GMPP hydrogel. This hydrogel is based on photo-sensitive gelatin methacryloyl (GelMA) as the matrix, and is loaded with pr萘洛尔 (PNL) - coated polydopamine (PDA) encapsulated hollow manganese dioxide (hMnO2) nanoparticles as the functional components. It integrates near-infrared photothermal antibacterial and sympathetic nerve microenvironment remodeling functions. Through the photothermal effect， it kills pathogens and releases pr萘洛尔 in response to acidic microenvironment to regulate neural activity， achieving synergistic enhancement of infection control and bone regeneration， providing a new path combining antibacterial and neural regulation for the treatment of infectious bone defects. 01 Research Background
Infectious bone defects are a significant challenge in the field of orthopedics. Their repair requires addressing two key issues simultaneously: On one hand, the colonization of pathogens triggers an immune response and secretes acidic metabolites, directly inhibiting osteoblast function and even causing tissue necrosis; on the other hand, trauma activates systemic and local stress responses, causing excessive activation of the sympathetic nervous system and accumulation of catecholamines, further interfering with the bone repair process. Current treatment strategies are difficult to simultaneously address infection clearance and regulation of the neural microenvironment, resulting in limited repair outcomes.
02 Main Content
This study focuses on the dual bottlenecks of "infection control" and "neural microenvironment disorder" in the repair of infectious bone defects, and designs and constructs a multifunctional GMPP hydrogel loaded with propranolol. Through precise integration of material structure and function, it achieves near-infrared light-triggered photothermal antibacterial and drug release in response to acidic microenvironment, thereby reshaping the sympathetic nervous microenvironment and counteracting the inhibitory effect of excessive sympathetic nerve activation on bone repair, ultimately achieving a synergistic effect of infection control and enhanced bone regeneration.
03 Research Design
Using photo-sensitive gel methacryloyl (GelMA) as the hydrogel matrix, a GMPP composite hydrogel is formed by loading propranolol (PNL) onto polydopamine (PDA)-coated hollow manganese dioxide (hMnO2) nanoparticles. The dual functional mechanism is designed: near-infrared light irradiation generates photothermal effect to kill bacteria, and the acidic microenvironment at the infection site triggers the controlled release of propranolol; in vitro experiments verify the photothermal antibacterial activity of the hydrogel, the release characteristics of propranolol, and its effects on osteogenic-related processes and sympathetic nerve stress responses; an SD rat model of infected cranial bone defect is established to evaluate the promotion effect of GMPP hydrogel on bone regeneration and its regulatory effect on sympathetic nerve activity in vivo.
04 Results
In vitro experiments confirmed that the GMPP hydrogel can effectively kill Staphylococcus aureus and Escherichia coli under near-infrared light irradiation; the propranolol released in the acidic microenvironment can counteract the angiogenesis inhibitory effect mediated by norepinephrine, alleviate the catabolic protein metabolism driven by sympathetic nerve stress, and thereby promote osteogenic-related processes; in vivo studies found that compared with non-infected areas, the sympathetic nerve activity in the infected bone defect area showed enhanced and prolonged characteristics, and the GMPP hydrogel could significantly promote bone regeneration in SD rats with infected cranial bone defects, its effect resulting from the synergistic effect of photothermal antibacterial and reshaping of the sympathetic nerve microenvironment.
05 Extension of Ideas
This study innovatively combines antibacterial treatment with neural regulation, proposing a "infection clearance - neural microenvironment remodeling - bone regeneration enhancement" collaborative repair paradigm, breaking through the limitation of traditional infectious bone defect treatment that only focuses on infection control and osteogenic promotion. The core idea lies in identifying and intervening in the disorder of the sympathetic nerve microenvironment as a factor hindering repair, achieving multi-targeted coordinated regulation through precise design of multifunctional materials, providing a new design direction for the development of bone repair materials in complex microenvironments, and highlighting the important research value of neural microenvironment regulation in the field of bone tissue engineering.
Original Source: - Author: Wenzhe Sun, Lian Zeng, Pengqing Zhang, Hongwei Lu, Bing Ye, Yizhou Wan, Yi Xu, Jialin Yu, Tingfang Sun, Yanzhen Qu, Bin Wu, Xiaohan Li, Kaifang Chen, Xiao Lv, Xiaodong Guo - Publication Date: 2025-10-17 - DOI: 10.1016/j.cej.2025.169736 - Journal: Chemical Engineering Journal
