Abstract
The effectiveness of stem-cell based therapy has been hampered by the limited availability of stem cell sources, immune rejection, and difficulties in clinical adoption and regulatory approval. These obstacles can be partially circumvented by using in situ tissue engineering that recruits the endogenous stem/progenitor cells and provides cues to direct stem cell phenotype. Here, decellularized bone scaffold is mechanically modified by coating of collagen (Col)/hydroxyapatite (HA) mixture with optimal ratio and loaded with chemokine stromal cell-derived factor-1α (SDF-1α), in which endogenous stem cell recruitment can be improved by chemokine and stem cell fate can be regulated by matrix elasticity of the scaffold. This study shows that mesenchymal stem cells (MSCs) osteogenesis in vitro was enhanced by matrix elasticity and SDF-1α, and endogenous MSCs recruitment in subcutaneous implantation of rat was increased by the release of SDF-1α from the scaffold, and bone regeneration in rabbit large bone defect model was significantly improved by matrix elasticity and SDF-1α. In short, this study provides a new insight for developing novel engineered cell-free bone substitutes by mechanical modification for tissue engineering and regenerative medicine.
Highlights
Stem-cell therapy holds great promise in tissue engineering and regenerative medicine
In situ bone regeneration can be partially circumvented by using the chemokine stromal cell-derived factor-1α (SDF-1α) that can recruit endogenous stem cells and osteogenic differentiation in situ can be achieved through a synergistic effect of appropriate mechanical cues
After culture for 3 weeks, the SDF-1α/Col/HA scaffold exhibited much more extracellular matrix (ECM) deposition and collagen deposition than other groups (Fig. 3). These results suggested that the SDF-1α/Col/HA scaffold has a positive effect on osteogenic differentiation and ECM secretion of mesenchymal stem cells (MSCs)
Summary
Stem-cell therapy holds great promise in tissue engineering and regenerative medicine. In situ bone regeneration can be partially circumvented by using the chemokine SDF-1α that can recruit endogenous stem cells and osteogenic differentiation in situ can be achieved through a synergistic effect of appropriate mechanical cues. In order to test this hypothesis, the present study will (1) fabricate and characterize a composite by loading 3D scaffold with optimal matrix elasticity with SDF-1α, (2) investigate the synergistic effects of SDF-1α and matrix mechanics on the fate of MSCs in vitro, (3) monitor and quantify the effects of SDF-1α on MSCs and inflammatory cells recruitment after subcutaneous transplantation in rats, and (4) evaluate the repair efficacy of the composite scaffold in rabbit large bone defect model in vivo
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