Injectable nanoporous microgels generate vascularized constructs and support bone regeneration in critical-sized
Matthew D Patrick1, Jeremy F Keys1, Harshini Suresh Kumar1
1Department of Biomedical Engineering, University of Kentucky, 760 Press Avenue, 138 Healthy Kentucky Research Building, Lexington, KY, 40536, USA.
Researchers developed novel chitosan and gelatin microgels to promote bone healing by supporting both bone formation and vascularization. These microgels effectively regenerate bone in large defects, offering a promising solution for engineered bone constructs.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Tissue Engineering
Background:
- Bone fracture healing requires both ossification and vascularization, with endothelial cells playing a synergistic role.
- Vascularizing large bone grafts is a significant challenge hindering clinical applications of engineered bone.
- Current engineered bone constructs face limitations in effectively integrating vascular networks.
Purpose of the Study:
- To develop a facile method for fabricating vascularized bone constructs using chitosan and gelatin-based microgels.
- To investigate the potential of these microgels in promoting osteogenesis of human mesenchymal stromal cells (MSC) and supporting endothelial network formation.
- To evaluate the efficacy of the microgel constructs in regenerating bone in a critical-sized defect model.
Main Methods:
- Fabrication of enzymatically degradable chitosan and gelatin-based microgels with specific physical properties (swelling ratio, polymer density, Young's modulus).
- Incorporation of hydroxyapatite into osteogenic microgels to mimic bone matrix and support MSC functions.
- Embedding vasculogenic microgels (gelatin-only) in 3D matrices to promote endothelial network formation.
- Evaluation of hybrid constructs combining osteogenic and vasculogenic microgels.
- In vivo assessment of bone regeneration in a murine critical-sized defect model.
Main Results:
- Microgels exhibited properties comparable to native skeletal tissues, with a Young's modulus conducive to osteogenesis and vasculogenesis.
- Osteogenic microgels supported MSC attachment, proliferation, and differentiation.
- Vasculogenic microgels promoted endothelial phenotype and vascular network formation.
- Hybrid constructs enhanced both osteogenic and vasculogenic functions.
- In vivo studies showed >95% defect closure in murine models within 12 weeks using osteogenic microgels.
Conclusions:
- Multifunctional microgels provide a promising strategy for creating vascularized bone constructs.
- These microgels can be administered minimally invasively and conformally fill large bone defects.
- The developed microgel system lays the foundation for designing multiphasic scaffolds for regenerating vascularized tissues.
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