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In situ controlled release of stromal cell-derived factor-1α and antimiR-138 for on-demand cranial bone regeneration.
Carbohydrate Polymers 2018 Februrary 16
Bone regeneration involves complex physiological processes, which is generally regulated and controlled by multiple bioactive molecules. In situ controlled release of combined bioactive factors in a spatiotemporal sequence for adapting the demand of bone regeneration is a desired strategy. In this study, nanoparticle/hydrogel composite system was constructed by incorporating stromal cell derived factor-1α (SDF-1α) and chitosan/tripolyphosphate/hyaluronic acid/antimiRNA-138 nanoparticles (CTH/antimiR-138 NPs) in chitosan/β-sodium glycerol phosphate (CS/GP) hydrogel for rat critical-size calvarial bone regeneration. The fast release of SDF-1α promoted the migration of mesenchymal stem cells (MSCs) for 6 d, while the sustained release of antimiR-138 from the nanoparticle/hydrogel compound enhanced the osteogenic differentiation of MSCs over 21 d. 8 weeks after surgery, calvarial specimens were evaluated by microcomputed tomography (μ-CT), histological analysis and immunohistochemistry. Comparing with blank group and hydrogel group, hydrogels incorporated with SDF-1α and/or CTH/antimiR-138 NPs significantly enhanced bone regeneration (p<0.05). In addition, the expression of collagen type-1 (COL-1), osteopontin (OPN) and osteocalcin (OCN) proteins were enhanced in the combined drug group (incorporated both SDF-1α and CTH/antimiR-138 NPs) in comparison to the hydrogel group. Our research indicated the in situ formation of NPs/hydrogel composite could provide temporal sequence-release of SDF-1α and CTH/antimiR-138 NPs for on-demand MSCs homing and cranial bone regeneration.
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