Papers by Author: X. Miao

Abstract: Vascular endothelial growth factor (VEGF) and bone morphogenetic proteins (BMP-7) are key regulators of angiogenesis and osteogenesis during bone regeneration. The aim of this study was to investigate the possibility of realizing sequential release of the two growth factors using a novel composite scaffold. Poly(lactic-co-glycolic acid) (PLGA)-Akermanite (AK) microspheres were used to make the composite scaffold, which was then loaded with BMP-7, followed by embedding in a gelatin hydrogel matrix loaded with VEGF. The release profiles of the growth factors were studied and selected osteogenic related markers of bone marrow stromal cells (BMSCs) were analysed. It was shown that the composite scaffolds exhibited a fast initial burst release of VEGF within the first 3 days and a sustained slow release of BMP-7 over the full period of 20 days. The in vitro proliferation and differentiation of the BMSCs cultured in the osteogenic medium were enhanced by 1 to 2 times, resulting from the additionally and sequentially release of growth factors from the PLGA-AK/gelatin composite scaffolds.

Abstract: Strong and tough, macroporous alumina/zirconia composites are superior to alumina scaffolds but still biologically inert to bone tissue, leading to poor tissue ingrowth and osteointegration. One way to solve this problem is applying a bioactive coating onto the pore walls of the macroporous composites. In this study, macroporous alumina/zirconia (20vol%) composites (scaffolds) were prepared by a vacuum infiltration method involving the use of strained (10%) compacts of the expanded polystyrene (EPS) beads (typically 1-2.8 mm in diameter). A bioactive glass (58S33C) coating (~ 20 μm) was applied on the pore walls of the macroporous composites by slurry dip coating and sintering at 1200 oC for 1 hour. A top or outer bioactive glass (58S33C) thin layer (< 10 μm) was further applied by sol dip coating and sintering at a low temperature (< 800 °C). The bioactive glass-coated macroporous alumina/zirconia composites had well interconnected pores, relatively large pore sizes (1-2 mm), medium porosities (60-66%), high compressive strengths (7.52 – 5.42 MPa), and high bioactivity (with an apatite layer formed within 24 hours in the simulated body fluid). The combination of the strong and ultrafine (if not nano-structured) macroporous scaffolds with the multiple or graded bioactive coatings represented a new generation of bone substitutes or permanent scaffolds for bone tissue regeneration.

Abstract: Polymer microspheres loaded with bioactive particles, biomolecules, proteins, and/or growth factors play important roles in tissue engineering, drug delivery, and cell therapy. The conventional double emulsion method and a new method of electrospraying into liquid nitrogen were used to prepare bovine serum albumin (BAS)-loaded poly(lactic-co-glycolic acid) (PLGA) porous microspheres. The particle size, the surface morphology and the internal porous structure of the microspheres were observed using scanning electron microscopy (SEM). The loading efficiency, the encapsulation efficiency, and the release profile of the BSA-loaded PLGA microspheres were measured and studied. It was shown that the microspheres from double emulsion had smaller particle sizes (3-50 m), a less porous structure, a poor loading efficiency (5.2 %), and a poor encapsulation efficiency (43.5%). However, the microspheres from the electrospraying into liquid nitrogen had larger particle sizes (400-600 m), a highly porous structure, a high loading efficiency (12.2%), and a high encapsulation efficiency (93.8%). Thus the combination of electrospraying with freezing in liquid nitrogen and subsequent freeze drying represented a suitable way to produce polymer microspheres for effective loading and sustained release of proteins.

Abstract: The limitations of autogenic, allogenic and xenogenic grafting methods have led to the development of synthetic grafts as an alternative. The aim of this study was to manufacture highly porous and well interconnected hydroxyapatite scaffolds and modify them with a poly(lactic-co-glycolic acid) (PLGA)-bioactive glass composite coating to achieve mechanical properties close to those of natural cancellous bones. In this study, hydroxyapatite scaffolds were prepared from a calcium phosphate cement (CPC) powder and cell culture using fibroblast cells was done to examine the cytotoxicity of the materials used for the scaffolds. The average pore size of the scaffolds was found to be 650μm and the total porosity was about 80%. The hydroxyapatite scaffolds without the coating had a mean compressive strength and a mean compressive modulus of 0.74 MPa and 20.46 MPa, respectively, which were in contrast to those of the scaffolds coated with the PLGA-bioacitve glass composite material (1.36 MPa and 24.58 MPa, respectively). The fibroblast cells were observed to proliferate well on the PLGA-bioactive glass coated scaffolds. The cells had also penetrated into the scaffold to a depth of approximately 2mm. Thus the scaffolds fabricated in this study exhibited a favourable porous structure and good cell response which are desirable for bone tissue engineering.

Abstract: Hydroxyapatite-zirconia composites have received much attention during the last decade due to their combination of the desirable mechanical properties of zirconia and the excellent bioactivity of hydroxyapatite (HA). However, thermal decomposition of the hydroxyapatite phase and reaction between the zirconia phase and the hydroxyapatite phase remain a major problem in the hydroxyapatite-zirconia composites. In this study, thermally stable and fluorine-substituted hydroxyapatite (Ca10(PO4)6(OH)0.8F1.2; coded as HA06F) was prepared by a sol-gel method to replace the hydroxyapatite. Yttria-stabilized zirconia (YTZP) was also prepared by a sol-gel method in order to produce HA06F-YTZP composites with 5, 10, 15, 20, 40, and 60 wt% YTZP by simple and cost-effective pressureless sintering. Thermogravimetric analysis (TGA) and x-ray diffraction (XRD) of the HA06F-YTZP composites showed that the thermal stability of the HA06F matrices could be maintained when the YTZP content did not exceed 20 wt% and for sintering temperatures less than 1400 oC. Dilatometric analysis and microstructural observation revealed that the YTZP phase in the HA06F-YTZP composites retarded the densification of the composites if the zirconia content was over 20 wt%. Electron scanning microscopy (SEM) and high resolution transmission electron microscopy (HR-TEM) of the HA06F-YTZP composites showed that the YTZP second phase had a size in the nanometer scale and the reaction between the HA06F phase and the zirconia phase was suppressed. Mechanical properties including the Knoop hardness, the Young’s modulus, and the fracture toughness of the HA06F-YTZP composites increased with the YTZP content until the optimal content of 20 wt%; higher YTZP contents led to low mechanical properties due to poor densification of the composites and the severe thermal decomposition of the HA06F phase. The optimal HA06F-20YTZP composite also showed desirable attachment and proliferation of osteoblast cells. Nevertheless, the study of the composite system indicated the limitations of the pressureless sintering technique. To achieve the full potential of the composites for medium or low load bearing applications, a pressure-assisted sintering technique would still be necessary.

Abstract: Porous biomaterials including porous bioceramics play important roles for hard tissue replacement and regeneration. I this paper, porous alumina (with and without zirconia addition) ceramics were produced via coating polyurethane (PU) foams with Al2O3 (ZrO2) slurries, followed by drying at room temperature and sintering at 1300 oC. The advantage of the PU foam method was the achieved high pore interconnectivity, but the mechanical properties of the porous ceramics were rather poor due to the high macroporosity and the high microporosity. To remove the microporosity and strengthen the porous alumina ceramics, a lanthanum-modified aluminosilicate (LAS) glass was used to infiltrate the alumina struts. Nevertheless, the resulting LAS-modified macroporous alumina ceramics would have no ability to bond to bone tissues. To impart a bioactivity (i.e. the ability of bone bonding) to the bioinert porous ceramics, a bioactive glass layer was applied by dipping with the bioactive glass slurry and sintering at 1200 oC. The twice coated porous alumina ceramics would exhibit high compressive strengths, allow bone tissue ingrowth, and form strong bonematerial integration. A biodegradable filler – calcium phosphate cement was also incorporated. A possible application of the porous bioceramics would be for the maxillofacial reconstruction.