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Published on: August 5, 2021
Early-Responsive Immunoregulation Therapy Improved Microenvironment for Bone Regeneration Via Engineered
Tingwei Lu1, Yuanqi Liu1, Xiangru Huang1
1Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, 200011, China.
Engineered extracellular vesicles (EVs) with high TIM3 expression reprogram macrophages to reduce inflammation, promoting bone healing. This strategy controls the early immune response for better bone regeneration.
Area of Science:
- Biomaterials Science
- Immunology
- Regenerative Medicine
Background:
- Overactivated inflammation impedes bone regeneration.
- Macrophages are key immune cells influencing bone repair outcomes.
- Modulating the early immune microenvironment is crucial for osteogenesis.
Purpose of the Study:
- To investigate the potential of TIM3-high extracellular vesicles (EVs) in modulating the immune microenvironment for enhanced bone regeneration.
- To target macrophages using engineered EVs to promote an anti-inflammatory state favorable for bone healing.
Main Methods:
- Engineered EVs with high TIM3 expression were developed.
- EVs were designed to be phagocytosed by macrophages, increasing TIM3-positive and M2 macrophage infiltration.
- The effect of EVs on macrophage cytokine secretion and inflammatory pathways (p38/MAPK) was analyzed.
- EVs were loaded into a hydrogel for sustained release.
Main Results:
- Engineered EVs promoted the infiltration and M2 polarization of macrophages.
- TIM3-positive macrophages secreted anti-inflammatory cytokines (IL-10, TGF-β1) by inhibiting the p38/MAPK pathway.
- EVs activated the Bmp2 promoter, enhancing macrophage BMP2 secretion and promoting osseointegration.
- Hydrogel-loaded EVs facilitated sustained release, recruiting anti-inflammatory macrophages and regulating the immune microenvironment.
Conclusions:
- TIM3-high EVs effectively reshape the early immune microenvironment by targeting macrophages.
- This approach offers a novel strategy for treating refractory bone defects by controlling excessive inflammation.
- The engineered EVs promote bone regeneration through immune modulation and enhanced osteogenesis.
