Declan M. Devine

Hydrogel/bioactive glass composites for bone regeneration applications: Synthesis and characterisation

Due to the deficiencies of current commercially available biological bone grafts, alternative bone graft substitutes have come to the forefront of tissue engineering in recent times. The main challenge for scientists in manufacturing bone graft substitutes is to obtain a scaffold that has sufficient mechanical strength and bioactive properties to promote formation of new tissue. The ability to synthesise hydrogel based composite scaffolds using photopolymerisation has been demonstrated in this study. The prepared hydrogel based composites were characterised using techniques including Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), Energy-dispersive X-ray spectrometry (EDX), rheological studies and compression testing. In addition, gel fraction, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), porosity and swelling studies of the composites were carried out. It was found that these novel hydrogel bioglass composite formulations did not display the inherent brittleness that is typically associated with bioactive glass based bone graft materials and exhibited enhanced biomechanical properties compared to the polyethylene glycol hydrogel scaffolds along. Together, the combination of enhanced mechanical properties and the deposition of apatite on the surface of these hydrogel based composites make them an ideal candidate as bone graft substitutes in cancellous bone defects or low load bearing applications.

Coating of carbon fiber-reinforced polyetheretherketone implants with titanium to improve bone apposition †‡

Carbon fiber-reinforced polyetheretherketone (CF/PEEK) is a thermoplastic composite biomaterial exhibiting properties suitable for load-bearing orthopedic implants. However, the hydrophobic surface of CF/PEEK implants induces the deposition of a peri-implant fibrous tissue capsule preventing bone apposition. However, if bone apposition was improved, the use of CF/PEEK in orthopedics could be increased as it has many advantages compared with metallic implants. In this study, CF/PEEK screws were coated with titanium (Ti) using two different techniques, namely vacuum plasma spraying (VPS) and physical vapor deposition (PVD) with uncoated screws as controls. These coatings were characterized and implanted in a loaded sheep tibia model. In the characterization of the screw surfaces using microscopy techniques, the uncoated screws were seen to have an irregular surface. The PVD coating appeared smooth and consistent, whereas the VPS coating appeared to be a rough coating with some inhomogeneities, which did not cover the entire surface area. Nevertheless, in the ex vivo analysis the VPS-coated screws had a screw removal torque which was statistically greater than uncoated and PVD-coated screws (p ≤ 0.002 for both comparisons). Additionally, the VPS-coated screws had a statistically higher bone contact area than the uncoated screws (p = 0.006), whereas no statistical difference was detected between VPS and PVD coating types (p = 0.11). Thereby illustrating that Ti coating of CF/PEEK screws significantly improve bone apposition and removal torque compared with uncoated CF/PEEK screws.

Review of Multifarious Applications of Poly (Lactic Acid)

ABSTRACT Poly (lactic acid) is considered to be a promising alternative to petroleum-based polymers due to its renewability, biodegradability, biocompatibility, and good mechanical properties. Because of the high cost, the applications of poly (lactic acid) were limited to the medical field. Over the past decade, improvements in polymerization allow the economical mass production of high molecular weight poly (lactic acid). Therefore, the applications of poly (lactic acid) have recently spread to domestic, commercial packaging, and textile applications. This review outlines the chemical, thermal characteristics of poly (lactic acid) and discusses the use of poly (lactic acid) in medical applications such as sutures, stents, drug carrier, orthopaedic devices, scaffolds, as well as commercial applications in textile and packaging fields with superior properties such as high wicking performance, good dyeability, antibacterial feature, good ultraviolet resistance, high water vapor transmission rates, shrink wrapping, and dead fold property. While the drawbacks of poly (lactic acid) utilized in these fields are also discussed. It is clear that the advantages of using poly (lactic acid) outlined in this review will ensure that the market for poly (lactic acid) products will continue to expand. GRAPHICAL ABSTRACT

Fabrication and in vitro biological evaluation of photopolymerisable hydroxyapatite hydrogel composites for bone regeneration

The aim of this study was to improve the bioactive and compressive properties of photopolymerisable polyethylene glycol hydrogels with the incorporation of hydroxyapatite at different loadings. The synthesis of pure hydroxyapatite was verified through Fourier transform infrared spectroscopy (FTIR) analysis by the complete reaction of all constituents. The formation of a bioactive layer of the hydrogel based composites was confirmed through the formation of carbonate hydroxyapatite after soaking the samples in simulated body fluid. The incorporation of hydroxyapatite into the system resulted in an increase in Young’s modulus from 4.36 to 12.73 MPa and an increase in the stress at limit value from 1.20 to 4.42 MPa. This was due to the hydroxyapatite absorbing the compressive load, the polymer matrix distributing the load, a reduction in swelling and the presence of physical crosslinking between both components. Drug dissolution testing showed that the release rate of a drug from the hydrogels was dependent on the molecular weight of the polymer and the type of drug used.

Compressive Strength and Bioactivity Properties of Photopolymerizable Hybrid Composite Hydrogels for Bone Tissue Engineering

The drug release capabilities of synthetic bone scaffolds have often been overlooked. In this study novel poly(ethylene) glycol and beta-tricalcium phosphate hydrogel composites were photopolymerized and evaluated in terms of mechanical strength, bioactivity, antimicrobial release profile, and the efficacy of released antimicrobials. Youngs modulus values ranged between 4.36 and 8.70 MPa. This increase was associated with the physical bonding interaction between polymer and bioceramic. Bioactivity was confirmed by the formation of globular crystals. Drug release studies showed the diffusion of vancomycin from hydrogel composites can be controlled by the hydrogels’ three-dimensional structure. Moreover, vancomycin loaded samples showed activity against Staphylococcus aureus.

Extraction Method Plays Critical Role in Antibacterial Activity of Propolis-Loaded Hydrogels

Extracted propolis has been used for a long time as a remedy. However, if the release rate of propolis is not controlled, the efficacy is reduced. To overcome this issue, extracted propolis was added to a cryogel system. Propolis collected from southern Brazil was extracted using different methods and loaded at different concentrations into polyvinyl alcohol (PVA) and polyacrylic acid hydrogels as carrier systems. The material properties were investigated with a focus on the propolis release profiles and the cryogel antibacterial properties against 4 different bacteria, namely: Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, and Pseudomonas putida. Swelling studies indicated that the swelling of the hydrogel was inversely related to propolis content. In addition, propolis release studies indicated a decreased release rate with increased propolis loading. PVA and PVA/polyacrylic acid-loaded propolis were effective against all 4 bacteria studied. These results indicate that the efficacy of propolis can be enhanced by incorporation into hydrogel carrier systems and that hydrogels with higher concentrations of propolis can be considered for use as bactericide dressing.

Calcium Phosphate Based Three-Dimensional Cold Plotted Bone Scaffolds for Critical Size Bone Defects

Bone substitutes, like calcium phosphate, are implemented more frequently in orthopaedic surgery to reconstruct critical size defects, since autograft often results in donor site morbidity and allograft can transmit diseases. A novel bone cement, based on β-tricalcium phosphate, polyethylene glycol, and trisodium citrate, was developed to allow the rapid manufacturing of scaffolds, by extrusion freeform fabrication, at room temperature. The cement composition exhibits good resorption properties and serves as a basis for customised (e.g., drug or growth factor loaded) scaffolds for critical size bone defects. In vitro toxicity tests confirmed proliferation and differentiation of ATDC5 cells in scaffold-conditioned culture medium. Implantation of scaffolds in the iliac wing of sheep showed bone remodelling throughout the defects, outperforming the empty defects on both mineral volume and density present in the defect after 12 weeks. Both scaffolds outperformed the autograft filled defects on mineral density, while the mineral volume present in the scaffold treated defects was at least equal to the mineral volume present in the autograft treated defects. We conclude that the formulated bone cement composition is suitable for scaffold production at room temperature and that the established scaffold material can serve as a basis for future bone substitutes to enhance de novo bone formation in critical size defects.

Melt Extruded Bioresorbable Polymer Composites for Potential Regenerative Medicine Applications

ABSTRACT Biodegradable polymers—polyethylene oxide and poly (ϵ-caprolactone)—were melt extruded with β-tricalcium phosphate. Breakdown analysis revealed that the percentage increase in bioceramic caused a prolonged degradation rate, with samples containing 20 wt% β-tricalcium phosphate losing significantly less weight over time in comparison to the control sample. Compression testing of samples following submission in aqueous environments revealed the composites exhibited enhanced strength with increasing bioceramic loading. The mechanical properties were significantly reduced over a period of 5 weeks. It was found that hot-melt extrusion of β-tricalcium phosphate is a viable and effective method of producing novel composite scaffolds with potential for regenerative medicine applications. GRAPHICAL ABSTRACT

The Development of Hot Melt Extruded Biocompatible Controlled Release Drug Delivery Devices

Novel fillers comprising chitosan and k-carrageenan were prepared via hot melt extrusion to examine the effect of percentage filler content on the properties of the scaffold. Cytotoxicity studies showed that hot melt extruded matrices resulted in high levels of compatibility when exposed to the NIH/3T3 cell line. These results indicate that these fillers may be used as a biocompatible, cheap, and viable functional excipients, which can be used to alter the release rate of hot melt extruded dosage forms and may be suitable for temporary biomedical applications such as orthopedic implants and drug delivery systems.

Characterization of an ovine bilateral critical sized bone defect iliac wing model to examine treatment modalities based on bone tissue engineering.

Critical sized bone defect (CSBD) animal models are used to evaluate and confirm efficacy and potency of new treatment modalities based on bone tissue engineering before the latter can be applied in clinical practice. In this study, a bilateral CSBD model in the iliac wings of sheep is described in detail. To demonstrate that this is a large animal CSBD model in sheep, bone healing within the defect left empty (negative control) or filled with autologous corticocancellous bone graft (clinical gold standard, positive control) was assessed using micro-CT, histology, histomorphometric, and fluorochrome analysis. After three months, new bone into the defect site was formed across the whole defect in the positive controls but limited to the edge of the defects in the negative controls. Bone volume in the positive controls was statistically higher than in the negative controls, with the latter having less than 10% new bone growth. There were no intraoperative or postoperative complications. The model described here represents a reliable and reproducible bilateral CSBD in sheep with low morbidity that can be used for in vivo evaluation of new treatment modalities based on bone tissue engineering.