Abstract
Bone tissue engineering technique is a promising strategy to repair large-volume bone defects. In this study, we developed a 3-dimensional construct by combining icariin (a small-molecule Chinese medicine), allogeneic bone marrow-derived mesenchymal stem cells (BMSCs), and a siliceous mesostructured cellular foams-poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (SMC-PHBHHx) composite scaffold. We hypothesized that the slowly released icariin could significantly promote the efficacy of SMC-PHBHHx/allogeneic BMSCs for repairing critical-size bone defects in rats. In in vitro cellular experiments, icariin at optimal concentration (10−6 mol/L) could significantly upregulate the osteogenesis- and angiogenesis-related genes and proteins, such as Runx2, ALP, osteocalcin, vascular endothelial growth factors, and fibroblast growth factors, as well as the mineralization of BMSCs. Icariin that was adsorbed onto the SMC-PHBHHx scaffold showed a slow release profile within a 2-week monitoring span. Eight weeks after implantation in calvarial critical-size bone defects, the constructs with icariin were associated with significantly higher bone volume density, trabecular thickness, trabecular number, and significantly lower trabecular separation than the constructs without icariin. Histomorphometric analysis showed that icariin was also associated with a significantly higher density of newly formed blood vessels. These data suggested a promising application potential of the icariin/SMC-PHBHHx/allogeneic BMSCs constructs for repairing large-volume bone defects in clinic.
Highlights
Large-volume bone defects may result from congenital nonunion, trauma, inflammation, and clinical treatments such as osteosarcoma-resection
We hypothesized that the slowly released icariin could significantly promote the efficacy of siliceous mesostructured cellular foams (SMC)-PHBHHx/ allogeneic bone marrow-derived mesenchymal stem cells (BMSCs) for repairing critical-size bone defects
Allogeneic BMSCs were seeded onto either icariin-containing or non-icariin-containing SMC-PHBHHx discs with a mild shaking for 72 hours at 37∘C under 5% CO2 before implantation
Summary
Large-volume bone defects may result from congenital nonunion, trauma, inflammation, and clinical treatments such as osteosarcoma-resection. Stem Cells International introduced to promote the healing of bone fractures and other bone metabolic diseases in clinics [5]. Their ability to modulate immune responses enables the application of allogeneic BMSCs without a substantial risk of immune rejection [5]. The highly porous and well-interconnected structure conferred excellent physicochemical, biological, and drug-release properties on this novel composite scaffold Hitherto, it remains unclear whether icariin can promote the efficacy of allogeneic BMSCs-based tissue engineering technique in repairing large-volume bone defects. We hypothesized that the slowly released icariin could significantly promote the efficacy of SMC-PHBHHx/ allogeneic BMSCs for repairing critical-size bone defects
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