Oncostatin-M functionalized cryogel microspheres for promoting diabetic bone defects regeneration
Rui Song1, Xiaojing Yuan1, Zhuo Wan2
1Department of Pediatrics, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, Beijing, 100081, PR China.
This study developed Oncostatin M (OSM) functionalized cryogel microspheres (OSM/MS) to enhance bone regeneration in diabetic conditions. OSM/MS effectively promoted osteogenesis, angiogenesis, and immunoregulation, showing great potential for treating diabetic bone defects.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Tissue Engineering
Background:
- Diabetic bone defects present significant healing challenges due to impaired regenerative capabilities.
- In situ bone tissue engineering strategies leverage endogenous repair mechanisms.
- Oncostatin M (OSM), a cytokine, is crucial for recruiting cells and promoting bone regeneration.
Purpose of the Study:
- To investigate the role of OSM in osteogenesis, angiogenesis, and immunoregulation.
- To develop OSM-functionalized cryogel microspheres (OSM/MS) for enhanced bone regeneration in diabetic models.
- To evaluate the efficacy of OSM/MS in promoting bone healing in diabetic conditions.
Main Methods:
- Systematic in vitro investigation of OSM bioactivity on bone marrow mesenchymal stromal cells (BMSCs), HUVECs, and macrophages.
- Fabrication of OSM-loaded porous GelMA cryogel microspheres (OSM/MS) using emulsification and gradient freeze-crosslinking.
- In vitro evaluation of OSM/MS biocompatibility, osteogenic and angiogenic potentials, and immunomodulatory effects.
- In vivo assessment of OSM/MS efficacy in an inflammatory diabetic rat calvarial defect model.
Main Results:
- OSM enhanced BMSC migration, osteogenic differentiation, and angiogenesis in vitro without inflammation.
- OSM/MS demonstrated excellent biocompatibility and promoted BMSC osteogenesis and HUVEC angiogenesis.
- OSM/MS modulated macrophage polarization to an anti-inflammatory M2 phenotype.
- In vivo, OSM/MS reduced osteoclast differentiation and enhanced bone regeneration in diabetic rats.
Conclusions:
- OSM/MS possess multifunctional properties, including stem cell recruitment, osteogenesis, immunomodulation, and angiogenesis induction.
- This bioactive microsphere strategy is effective for managing challenging diabetic bone defects.
- The developed OSM/MS holds significant potential for clinical translation in treating diabetic bone defects, offering a cell-free, minimally invasive approach.
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