Hypoxia-mimicking 3D bioglass-nanoclay scaffolds promote endogenous bone regeneration

Abstract

Large bone defect repair requires biomaterials that promote angiogenesis and osteogenesis. In present work, a nanoclay (Laponite, XLS)-functionalized 3D bioglass (BG) scaffold with hypoxia mimicking property was prepared by foam replication coupled with UV photopolymerization methods. Our data revealed that the incorporation of XLS can significantly promote the mechanical property of the scaffold and the osteogenic differentiation of human adipose mesenchymal stem cells (ADSCs) compared to the properties of the neat BG scaffold. Desferoxamine, a hypoxia mimicking agent, encourages bone regeneration via activating hypoxia-inducible factor-1 alpha (HIF-1α)-mediated angiogenesis. GelMA-DFO immobilization onto BG-XLS scaffold achieved sustained DFO release and inhibited DFO degradation. Furthermore, in vitro data demonstrated increased HIF-1α and vascular endothelial growth factor (VEGF) expressions on human adipose mesenchymal stem cells (ADSCs). Moreover, BG-XLS/GelMA-DFO scaffolds also significantly promoted the osteogenic differentiation of ADSCs. Most importantly, our in vivo data indicated BG-XLS/GelMA-DFO scaffolds strongly increased bone healing in a critical-sized mouse cranial bone defect model. Therefore, we developed a novel BG-XLS/GelMA-DFO scaffold which can not only induce the expression of VEGF, but also promote osteogenic differentiation of ADSCs to promote endogenous bone regeneration.

Vascularized bone regeneration accelerated by 3D-printed nanosilicate-functionalized polycaprolactone scaffold

“…Therefore, it is reasonable to presume that the PCL/LAP scaffold stimulated extracellular matrix mineralization by accelerating Col-1α1 synthesis to provide a matrix for osteoid formation, which might be attributed to the increased RUNX2 level induced by LAP released from PCL/LAP. Similar trends were observed in previous studies of LAP-containing biomaterials [ 21 , 22 , 40 , 41 ].…”

“…The degradation products of LAP consist of silicon [Si(OH) 4 ], magnesium (Mg 2+ ) and lithium (Li + ) ions [ 37 , 48 ]. All these degradation products have been regarded as playing considerable roles in osteogenesis and angiogenesis [ 16 , 37 , 40 ]. These results confirm the osteoconductive and osteoinductive properties of LAP-incorporated PCL in vivo and suggest that LAP-incorporated PCL can be envisioned as a promising candidate for vascularized bone regeneration.…”

The effect of hypoxia on myogenic differentiation and multipotency of the skeletal muscle-derived stem cells in mice

“…Furthermore, it has been reported that HX enhances vascular endothelial growth factor ( VEGF ) and interleukin 6 ( IL6 ) expression as well as it coordinates stem cells homing and mobilization [ 64 ]. Along the line, using biomaterials scaffold incorporated with HX inducing agents (Desferoxamine) to enhance OD of adipose tissue-derived mesenchymal stem cells reported the efficiency of scaffolds to upregulate HIF1α and VEGF expression and to improve OD in humans [ 65 ].…”

Anisotropic silk nanofiber layers as regulators of angiogenesis for optimized bone regeneration

“…The cytocompatibility and bioactivity of these matrices were further improved by changing nano-micro structures, anisotropic topography, degradation behavior and mechanical performance [ [16] , [17] , [18] , [19] ]. Various polymers, mineral nanomaterials, and biomacromolecules were also introduced into silk-based bone matrices, endowing them with angiogenesis and osteogenesis inducing and control features [ 5 , 20 , 21 ]. However, a gap maintains for SF matrices to further improve the angiogenic and osteogenic capacity in a dynamic fashion for bone regeneration.…”