Abstract
Reconstruction of large bone defects remains a clinical challenge because current approaches involving surgery and bone grafting often do not yield satisfactory outcomes. For artificial bone substitutes, angiogenesis plays a pivotal role to achieve the final success of newly regenerated bone. In this study, dexamethasone-loaded biphasic calcium phosphate nanoparticles/collagen composite scaffolds with several types of concave microgrooves were prepared for simultaneous promotion of angiogenesis and osteogenesis. Microgrooves in the scaffolds were supposed to guide the assembly of human umbilical vascular endothelial cells (HUVECs) into well aligned tubular structures, thus promoting rapid angiogenesis. The scaffolds were used for co-culture of HUVECs and human bone marrow-derived mesenchymal stem cells. Subcutaneous implantation in mice showed that more blood vessels and newly formed bone were observed in the microgrooved composite scaffolds than in the control scaffold. Scaffold bearing parallel microgrooves with a concave width of 290 µm and a convex ridge width of 352 µm showed the highest promotion effect on angiogenesis and osteogenesis among the parallelly microgrooved composite scaffolds. The scaffolds bearing a grid network had further superior promotion effect to the scaffolds bearing parallel microgrooves. The results indicated that microgrooves in the composite scaffolds facilitated angiogenesis and stimulated new bone formation. The microgrooved composite scaffolds should be useful for repairing of large bone defects.
Highlights
By cell death in regions far from the capillaries[6]
The composite scaffolds were used for co-culture of human umbilical vascular endothelial cells (HUVECs) and human bone marrow-derived mesenchymal stem cells to investigate their effects on angiogenesis and osteogenesis by in vitro cell culture and in vivo implantation
The DEX-BCP-Col composite scaffolds were used for co-culture of HUVECs and human bone marrow-derived mesenchymal stem cells (hMSCs) for simultaneous promotion of angiogenesis and osteogenesis
Summary
By cell death in regions far from the capillaries[6]. Due to the diffusion limit of oxygen and nutrients, generally the reconstructed tissue thicker than 400 μm should be vascularized to maintain the viability[4]. Incorporation of biological and pharmaceutical factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor in tissue engineering scaffolds has been generally used for promotion of angiogenesis[7,8]. Some concerns with this approach remain, such as instability, uncontrollable dose, high cost, short half-life and increased risk of tumorigenesis[9,10]. Bone tissue engineering scaffolds should have osteoconductive and osteoinductive functions to enhance regeneration of large bone defects Protein growth factors such as transform growth factor-β and bone morphogenetic protein-2 (BMP-2) have been frequently incorporated in scaffolds to increase their osteogenesis-promoting effects[18,19]. The composite scaffolds were used for co-culture of HUVECs and human bone marrow-derived mesenchymal stem cells (hMSCs) to investigate their effects on angiogenesis and osteogenesis by in vitro cell culture and in vivo implantation
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