Synergistic effect of stem cells from human exfoliated deciduous teeth and rhBMP-2 delivered by injectable nanofibrous microspheres with different surface modifications on vascularized bone regeneration

Abstract

To provide a suitable 3D microenvironment for bone regeneration, we selected the injectable poly (l-lactic acid) nanofibrous microspheres (PLLA NF-Ms) with different surface modifications to serve as cell micro-carriers or protein vehicles on-demand. Results showed that polydopamine (PDA) modified NF-Ms (PDA-NF-Ms) exhibited good affinity for stem cells from human exfoliated deciduous teeth (SHED), and Heparin-Dopamine (Hep-Dopa) conjugated with NF-Ms (Hep-Dopa NF-Ms) are able to immobilize and slowly release recombinant human bone morphogenic protein-2 (rhBMP-2) efficiently. In vivo evaluations were carried out in both ectopic subcutaneous implantation and orthotopic cranial bone defect nude mouse models (φ = 4 mm). The results suggested that PDA-NF-Ms could support SHED survival over 4 weeks. All experimental groups with SHED/PDA-NF-Ms engraftment showed angiogenesis activity. But, no effect of SHED/PDA-NF-Ms on osteogenesis was found in ectopic implantation, which is different from the result in cranial defect. The rhBMP-2 released from Hep-Dopa NF-Ms could significantly guide bone tissue regeneration in both ectopic and orthotopic site. At 8 weeks, both BMP-2 group and dual group showed large amounts of bone formation in situ, despite the fact that quantitative results of micro-CT did not demonstrate significant difference between them. More blood vessels were observed in SHED and Dual groups, which verifies the quality improvement of regenerated osseous tissues. Regeneration of vascularized bone tissue was, thus, highly expected upon implanting SHED/PDA-NF-Ms and rhBMP-2-loaded Hep-Dopa NF-Ms together. The strategy developed in this study represents a promising method for satisfactorily promoting bone regeneration.