Journal
REGENERATIVE BIOMATERIALS
Volume 6, Issue 2, Pages 89-98Publisher
OXFORD UNIV PRESS
DOI: 10.1093/rb/rbz008
Keywords
bone regeneration; cortical bone-like; osteon-mimetic; calcium phosphate nucleated nanofiber microsheet; vascularized osteogenesis
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Funding
- National Science Foundation [CBET1403545, IIP150024]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [AR063745]
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The objective of this work was to fabricate a rigid, resorbable and osteoconductive scaffold by mimicking the hierarchical structure of the cortical bone. Aligned peptide-functionalize nanofiber microsheets were generated with calcium phosphate (CaP) content similar to that of the natural cortical bone. Next, the CaP-rich fibrous microsheets were wrapped around a microneedle to form a laminated microtube mimicking the structure of an osteon. Then, a set of the osteon-mimetic microtubes were assembled around a solid rod and the assembly was annealed to fuse the microtubes and form a shell. Next, an array of circular microholes were drilled on the outer surface of the shell to generate a cortical bone-like scaffold with an interconnected network of Haversian- and Volkmann-like microcanals. The CaP content, porosity and density of the bone-mimetic microsheets were 240 wt%, 8% and 1.9 g/ml, respectively, which were close to that of natural cortical bone. The interconnected network of microcanals in the fused microtubes increased permeability of a model protein in the scaffold. The cortical scaffold induced osteogenesis and vasculogenesis in the absence of bone morphogenetic proteins upon seeding with human mesenchymal stem cells and endothelial colony-forming cells. The localized and timed-release of morphogenetic factors significantly increased the extent of osteogenic and vasculogenic differentiation of human mesenchymal stem cells and endothelial colony-forming cells in the cortical scaffold. The cortical bonemimetic nature of the cellular construct provided balanced rigidity, resorption rate, osteoconductivity and nutrient diffusivity to support vascularization and osteogenesis.
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