The macro-pore sizes of porous scaffold play a key role for regulating ectopic osteogenesis and angiogenesis but many researches ignored the influence of interconnection between macro-pores with different sizes. In order to accurately reveal the relationship between ectopic osteogenesis and macro-pore sizes in dorsal muscle and abdominal cavities of dogs, hydroxyapatite (HA) scaffolds with three different macro-pore sizes of 500–650, 750–900 and 1100–1250 µm were prepared via sugar spheres-leaching process, which also had similar interconnecting structure determined by keeping the d/s ratio of interconnecting window diameter to macro-pore size constant. The permeability test showed that the seepage flow of fluid through the porous scaffolds increased with the increase of macro-pore sizes. The cell growth in three scaffolds was not affected by the macro-pore sizes. The in vivo ectopic implantation results indicated that the macro-pore sizes of HA scaffolds with the similar interconnecting structure have impact not only the speed of osteogenesis and angiogenesis but also the space distribution of newly formed bone. The scaffold with macro-pore sizes of 750–900 µm exhibited much faster angiogenesis and osteogenesis, and much more uniformly distribution of new bone than those with other macro-pore sizes. This work illustrates the importance of a suitable macro-pore sizes in HA scaffolds with the similar interconnecting structure which provides the environment for ectopic osteogenesis and angiogenesis.
The surface microstructures of calcium phosphate ceramics play an essential role in determining bone regeneration. However, it is difficult to produce micro/nano-structures on the surface of the porous hydroxyapatite (HA) scaffolds. In this study, we successfully developed and fabricated various micro/nano-structured surfaces on the HA scaffolds in copper ion (Cu2+)-containing solutions under hydrothermal conditions. The micro/nano-structures on the surface of the HA scaffolds were controlled by modulating the Cu2+ concentrations during the hydrothermal process. With an increase in the Cu2+ concentration, the surface morphology of the HA scaffolds changed significantly from sphere-like to flower-like, before becoming nano-structures. These findings indicated that the Cu2+ concentration affects the morphologies of calcium phosphate coatings that grow on the HA scaffolds. In vitro endothelial cell (EC) cultures showed that the cell proliferation was significantly enhanced when cultured on the flower-like morphology compared with other morphologies. Furthermore, an in vivo test in New Zealand rabbits demonstrated that the HA scaffold with the flower-like surface resulted in more angiogenesis compared with the control scaffold. This copper-assisted hydrothermal deposition process provides a simple and controllable route for engineering a micro/nano-structured surface on the HA scaffolds, which has benefits in terms of angiogenesis and bone regeneration.
A Cu/Zn co-incorporated BCP scaffold-derived GDF-5 sustained release system was successfully prepared and exhibited improved angiogenic and osteogenic capacities.
Microstructure and chemical constitution are important factors affecting the biological activity of biomaterials. This study aimed to fabricate hydroxyapatite (HAp) particles with both micro/nanohybrid structure and Cu doping to promote osteogenic differentiation and antibacterial property. In the presence of inositol hexakisphosphate (IP6), micro/nano-structured and Cu-doped HAp (HAp-IP6-Cu) microspheres were successfully fabricated via hydrothermal method. Morphological observation showed that HAp-IP6-Cu microspheres with a diameter of 3.1-4.1 μm were chrysanthemum-like and composed of nano-flakes approximately 50 nm in thickness. Compared with the HAp micro-rods or IP6 modified HAp (HAp-IP6) microspheres, HAp-IP6-Cu microspheres had a larger specific surface area, better hydrophilicity and stronger ability to adsorb bovine serum albumin. To evaluate the synergistic effects of micro/nanohybrid structure and Cu on cell behavior, rat calvarial osteoblasts (RCOs) were cultured on HAp-IP6-Cu, HAp-IP6 and HAp layers as well as their extracts, respectively. Results demonstrated that HAp-IP6-Cu layer promoted the adhesion, proliferation and osteogenic differentiation of RCOs. The cells grew on HAp-IP6-Cu and HAp-IP6 layers exhibited greater spreading than those on HAp layer. In addition, quantitative test by the agar disk diffusion technique found that HAp-IP6-Cu microspheres were effectively against S taphylococcus aureus and E scherichia coli. These results demonstrated that HAp-IP6-Cu microspheres may be a potential candidate as a bioactive and anti-infective biomaterial for bone regeneration.
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