Bone Tissue Regeneration Using Mesenchymal Stem Cell-Encapsulated Acidic Microparticle-Filled Collagen Gel

Bone regenerative therapies have been extensively studied to improve the quality of clinical treatments for various bone defects.  These therapies integrate an assortment of bioactive molecules, stem and progenitor cells, and biomaterials to orchestrate osteogenesis.  These approaches widely use collagen gels to sequester transplanted cells in bone defects and further stimulate cellular osteogenic activities.  However, collagen gels are often plagued by a limited control of the mechanical rigidity and mineral deposition, which leads to an unsatisfactory regeneration of mineralized bone with the desired osteointegration.  This study presents a novel method to enhance both the mechanical rigidity and mineral deposition of collagen gels by introducing poly(lactic-co-glycolic acid) (PLGA) microparticles in the gels. We found that incorporation PLGA particles at a concentration of 10 mg/mL increased the storage modulus of the collagen gels from 4 to 36 Pa.  The osteogenic differentiation of mesenchymal stem cells (MSCs) within the soft PLGA particle-filled collagen gels generated a hard mineralized matrix, of mostly hydroxyapatite. Finally, implantation of MSC-encapsulating PLGA microparticle-filled collagen gels on chick chorioallantoic membranes (CAMs) generated mineralized tissues similar to woven bone tissue.  Overall, the material system designed in this study displays a strong potential to significantly improve clinical treatments of critical bone tissue defects.