Xia Zhong

Surface modification of poly(propylene carbonate) by aminolysis and layer-by-layer assembly for enhanced cytocompatibility

Poly(propylene carbonate) (PPC) is a biodegradable polymer with desirable mechanical properties for bone and cartilage repair. However, the poor biocompatibility impedes its applications in tissue engineering. The aim of this study was to evaluate the effect of surface modification of PPC on the improvement of its cytocompatibility. The combination of aminolysis and layer-by-layer (LBL) assembly techniques was used to modify the PPC surface. The results of ATR-FTIR measurement demonstrated that PPC was aminolyzed by polyethylenimine (PEI) at specific reaction conditions and the degree of aminolyzation was quantitatively determined by ninhydrin method. Positively charged PEI and negatively charged gelatin were alternatively deposited on the aminolyzed PPC membranes at pH 7.4, which formed polyelectrolyte multilayers surface with gelatin as the outermost layer. The presence of amino groups on the aminolyzed PPC and gelatin on the multilayers had significant impact on enhancing the hydrophilicity of PPC. Fibroblast and primary human osteoblasts (HOBs) were used to assess the cytocompatibility of PPC. The deposition of PEI and gelatin bilayers on PPC remarkably promoted both fibroblast and HOBs cell attachment, spreading and growth. In particular, the osteogenic gene expression of HOBs cultured on the multilayers modified PPC was substantially increased. The aminolysis followed by LBL assembly is a convenient and cost effective technique for enhancing cell attachment and proliferation. The product has high potential for musculoskeletal tissue engineering applications due to its desirable mechanical strength and tunable cytocompatibility.

Fabrication of biomimetic poly(propylene carbonate) scaffolds by using carbon dioxide as a solvent, monomer and foaming agent

The aim of this study was to develop an environmentally friendly process for the fabrication of three dimensional (3D) biomimetic scaffolds from biodegradable poly(propylene carbonate) (PPC). Prior to production of scaffolds, PPC was synthesized using a one-pot process in which the zinc glutarate catalyst was first fabricated in a supercritical CO2 system. The scaffolds were then prepared by gas foaming/salt leaching followed by aminolysis and layer-by-layer (LBL) gelatin assembly on the surface. The pore size and interconnectivity were controlled by the variation of gas foaming process parameters such as temperature, CO2 pressure, depressurization rate and particle size of salt (NaCl). The pore size was within the range of 116 ± 53 to 418 ± 84 μm and the porosity was between 69.8 and 92.3%. The results of micro-CT scan analysis demonstrated that porosity and pore interconnectivity were enhanced by increasing the pore size. However, the compressive modulus of hydrated scaffolds was decreased from 380 ± 90 to 200 ± 50 kPa, when the pore size was increased from 232 ± 91 to 411 ± 108 μm. The results of fluorescence microscopy demonstrated that gelatin was uniformly deposited on the 3D scaffolds. Surface modification of hydrophobic PPC scaffolds substantially increased the fibroblast cells attachment, penetration, and proliferation. The results of this study demonstrated the feasibility of eliminating toxic organic solvents in the synthesis of a solid based catalyst and processing PPC polymer into tissue scaffolds. The clean technology developed will be of great value for large scale production of biodegradable PPC that can be used for many purposes such as packaging products and plastic bags. In addition, it was shown that PPC can be considered as an alternative biomaterial for tissue engineering applications.

Delicate Refinement of Surface Nanotopography by Adjusting TiO2 Coating Chemical Composition for Enhanced Interfacial Biocompatibility

Surface topography and chemistry have significant influences on the biological performance of biomedical implants. Our aim is to produce an implant surface with favorable biological properties by dual modification of surface chemistry and topography in one single simple process. In this study, because of its chemical stability, excellent corrosion resistance, and biocompatibility, titanium oxide (TiO2) was chosen to coat the biomedical Ti alloy implants. Biocompatible elements (niobium (Nb) and silicon (Si)) were introduced into TiO2 matrix to change the surface chemical composition and tailor the thermophysical properties, which in turn leads to the generation of topographical features under specific thermal history of plasma spraying. Results demonstrated that introduction of Nb2O5 resulted in the formation of Ti0.95Nb0.95O4 solid solution and led to the generation of nanoplate network structures on the composite coating surface. By contrast, the addition of SiO2 resulted in a hairy nanostructure and coexistence of rutile and quartz phases in the coating. Additionally, the introduction of Nb2O5 enhanced the corrosion resistance of TiO2 coating, whereas SiO2 did not exert much effect on the corrosion behaviors. Compared to the TiO2 coating, TiO2 coating doped with Nb2O5 enhanced primary human osteoblast adhesion and promoted cell proliferation, whereas TiO2 coatings with SiO2 were inferior in their bioactivity, compared to TiO2 coatings. Our results suggest that the incorporation of Nb2O5 can enhance the biological performance of TiO2 coatings by changing the surface chemical composition and nanotopgraphy, suggesting its potential use in modification of biomedical TiO2 coatings in orthopedic applications.

Nanoscale Chemical Interaction Enhances the Physical Properties of Bioglass Composites

Bioglasses are favorable biomaterials for bone tissue engineering; however, their applications are limited due to their brittleness. In addition, the early failure in the interface is a common problem of composites of bioglass and a polymer with high mechanical strength. This effect is due to the phase separation, nonhomogeneous mixture, nonuniform mechanical strength, and different degradation properties of two compounds. To address these issues, in this study a nanoscale interaction between poly(methyl methacrylate) (PMMA) and bioactive glass was formed via silane coupling agent (3-trimethoxysilyl)propyl methacrylate (MPMA). A monolith was produced at optimum composition from this hybrid by the sol-gel method at 50 °C with a rapid gelation time (<50 min) that possessed superior physicochemical properties compared to pure bioglass and physical mixture. For instance, the Youngs modulus of bioglass was decreased 40-fold and the dissolution rate of silica was retarded 1.5-fold by integration of PMMA. Prolonged dissolution of silica fosters bone integration due to the continuous dissolution of bioactive silica. The primary osteoblast cells were well anchored and cell migration was observed on the surface of the hybrid. The in vivo studies in mice demonstrated that the integrity of the hybrids was maintained in subcutaneous implantation. They induced mainly a mononuclear phagocytic tissue reaction with a low level of inflammation, while bioglass provoked a tissue reaction with TRAP-positive multinucleated giant cells. These results demonstrated that the presence of a nanoscale interaction between bioglass and PMMA affects the properties of bioglass and broadens its potential applications for bone replacement.

Synthesis of a biodegradable polymer in gas expanded solution: effect of the process on cytocompatibility

The aim of this study was to investigate the feasibility of eliminating organic solvent consumption for the synthesis of biodegradable poly(lactide ethylene oxide fumarate) (PLEOF). A gas expanded solution comprised of high pressure carbon dioxide (CO2) and dichloromethane (DCM) or poly(ethylene glycol) (PEG) was used as an alternative medium for the synthesis of PLEOF. The effect of pressure (50–150 bar), temperature (25–50 °C) and the amount of DCM on the yield, molecular weight and thermal properties of PLEOF was examined. The results of 1H NMR and ATR-FTIR analysis confirmed that it is possible to conduct the PLEOF synthesis in a high pressure CO2 expanded solution as a reaction medium and acquire similar characteristics compared to the conventional method using neat DCM. A comparable yield was achieved in a high pressure CO2 expanded solution process even when DCM was decreased to only 14% of the amount used in the conventional method. Increasing the pressure from 50 to 150 bar had no significant effect on the yield. In addition, DCM could be completely eliminated from the polymerisation by increasing the temperature to 50 °C and pressure to 100 bar. Under these conditions, the synthesis was carried out in PEG expanded solution due to the melting point depression effect of CO2. It is, therefore, viable to conduct the polymerisation of PLEOF in gas expanded solution as a benign solvent and can either substantially reduce or eliminate the consumption of volatile organic solvents. The synthesised PLEOF was also crosslinked with poly(ethylene glycol) diacrylate (PEGDA) as a non-toxic crosslinker to produce an injectable hydrogel. The hydrogel prepared from PLEOF that was synthesised by gas expanded solution had better mechanical properties and less toxicity to primary human osteoblast cells. This study demonstrated that the synthesis process can have a significant impact on improving the physical properties and biological activity of the PLEOF polymer.

Chitosan/Poly (ε-Caprolactone) Composite Hydrogel for Tissue Engineering Applications

The aim of this study was to fabricate the three-dimensional (3D) porous structure of chitosan/Poly (e-caprolactone) (PCL) hydrogels with improved mechanical properties for tissue engineering applications. A modified emulsion lyophilization technique was developed to produce a 3D chitosan/PCL scaffold. The addition of 25 wt% and 50 wt% of PCL into chitosan substantially enhanced the compressive strength of hydrogel 160% and 290%, respectively, compared to pure chitosan hydrogel. The result of ATR-FTIR corroborates that PCL and chitosan physically co-existed in the composite mixture. The composites comprised of uniform macro (59.7 ±14.4 μm) and micro (4.4 ± 1.5 μm) pores as observed in the SEM images. The composites acquired in this study with homogeneous porous structure and improved intergrity may have a high potential for the production of 3D scaffolds that can be used in various tissue engineering applications. The results of confocal fluorescence microscopy confirmed that fibroblast cells were proliferated in the 3D structure of these composite scaffolds.