Luke M. Geever

The synthesis of novel pH-sensitive poly(vinyl alcohol) composite hydrogels using a freeze/thaw process for biomedical applications

Physically cross-linked hydrogels composed of 75% poly(vinyl alcohol) PVA and 25% poly(acrylic acid) were prepared by a freeze/thaw treatment of aqueous solutions. Between 0.5 and 1wt% of aspirin was incorporated into the systems. The purpose of the research was the development of a novel pH-sensitive hydrogel composite for the delivery of aspirin to wounds. Extensive research has being conducted on freeze/thaw poly(vinyl alcohol) hydrogels for use in active pharmaceutical ingredient (API) delivery. However very little research has been reported on the effects of an API on the overall properties of a freeze/thaw hydrogel. From the rheological analysis undertaken it was apparent that aspirin has a limiting effect on the formation of hydrogen bonding leading to hydrogels with reduced mechanical strength. To counteract this, a novel hydrogel system was developed encompassing a reinforcing film in the centre of the hydrogels. Freezing profiles were obtained to gain a better knowledge of the freezing behaviour of the hydrogels during the formation stage. Thermograms obtained from modulated differential scanning calorimetry (MDSC) indicated that the aspirin lowered the glass transition temperatures (T(g)) of the constituent polymers. The pH-sensitive nature of the hydrogels was apparent from solvent uptake studies carried out. Increasing alkaline media led to a greater degree of swelling due to increased ionisation of PAA. The hydrogels exhibited non-Fickian release kinetics. The release rates were relatively slow with total release achieved at between 30 and 40 h. The quantity of drug incorporated was found to influence the release rates considerably.

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.

Cell encapsulation and cryostorage in PVA–gelatin cryogels: incorporation of carboxylated ε‐poly‐L‐lysine as cryoprotectant

It is desirable to produce cryopreservable cell‐laden tissue‐engineering scaffolds whose final properties can be adjusted during the thawing process immediately prior to use. Polyvinyl alcohol (PVA)‐based solutions provide platforms in which cryoprotected cell suspensions can be turned into a ready‐to‐use, cell‐laden scaffold by a process of cryogelation. In this study, such a PVA system, with DMSO as the cryoprotectant, was successfully developed. Vascular smooth muscle cell (vSMC)‐encapsulated cryogels were investigated under conditions of cyclic strain and in co‐culture with vascular endothelial cells to mimic the environment these cells experience in vivo in a vascular tissue‐engineering setting. In view of the cytotoxicity DMSO imposes with respect to the production procedure, carboxylated poly‐L‐lysine (COOH–PLL) was substituted as a non‐cytotoxic cryoprotectant to allow longer, slower thawing periods to generate more stable cryogels. Encapsulated vSMC with DMSO as a cryoprotectant responded to 10% cyclic strain with increased alignment and proliferation. Cells were stored frozen for 1 month without loss of viability compared to immediate thawing. SMC‐encapsulated cryogels also successfully supported functional endothelial cell co‐culture. Substitution of COOH–PLL in place of DMSO resulted in a significant increase in cell viability in encapsulated cryogels for a range of thawing periods. We conclude that incorporation of COOH–PLL during cryogelation preserved cell functionality while retaining fundamental cryogel physical properties, thereby making it a promising platform for tissue‐engineering scaffolds, particularly for vascular tissue engineering, or cell preservation within microgels. Copyright

A rapid crosslinking injectable hydrogel for stem cell delivery, from multifunctional hyperbranched polymers via RAFT homopolymerization of PEGDA

Stem cell therapies have attracted much attention for the last few decades in the field of regenerative medicine and tissue engineering. The 3-dimensional (3D) microenvironment surrounding the transplanted stem cells plays an essential role that influences the cell fate and behaviors. Thus advanced functional biomaterials and extracellular matrix (ECM) replacements with adjustable chemical, mechanical and bioactive properties are requisites in this field. In this study, PEG-based hyperbranched multifunctional homopolymers were developed via RAFT homopolymerization of the divinyl monomer of poly(ethylene glycol) diacrylate (PEGDA). Due to its high degree of multi-acrylate functionality, the hyperbranched polyPEGDA can rapidly crosslink with a thiolated hyaluronic acid under physiological conditions and form an injectable hydrogel for cell delivery. In addition, by simply varying the synthesis conditions such as the reaction time and the ratio of the monomer to the chain transfer agent (CTA), the polymer molecular weight, acrylate functionality degree and the cyclized/hyperbranched polymeric architecture can be finely controlled in a one-step reaction. The gelation speed and the mechanical properties of this hydrogel can be easily adjusted by altering the crosslinking conditions. Rat adipose-derived stem cells (rASCs) were embedded into the in situ crosslinked hydrogels, and their cellular behavior such as the morphology, viability, metabolic activity and proliferation were fully evaluated. The results suggested that the hydrogel maintained good cell viability and it can be easily modified with other bioactive signals, which provide this injectable hydrogel delivery system with good potential for polymeric biomaterials and tissue regeneration applications.

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.

Development of novel chitosan-poly(N,N-diethylacrylamide) IPN films for potential wound dressing and biomedical applications

Novel interactive and thermoresponsive interpenetrating polymer network (IPN) films, which are transparent, permeable to oxygen, and have the potential to be easily stripped from a wound bed, were synthesised using rapid photopolymerisation and crosslinking of DEAAm in the presence of chitosan. This study provides the first evaluation and optimisation of a UV-polymerised chitosan–PDEAAm IPN composite film for application in wound dressings. FTIR spectroscopy and DSC analysis were used to initially characterise the resulting films. Modulated differential scanning calorimetry results showed that the dressings exhibited lower critical solution temperatures in the desired range, while the samples were also observed to undergo temperature-dependent swelling behaviour. This thermosensitive property would potentially allow the dressings to be easily detachable, which would enable frequent dressing changes if desired without causing further injury to healing tissues. Furthermore, the water content values recorded are in the typical and desired ranges for commercial wound dressings.

Photopolymerised thermo-responsive poly(N,N-diethylacrylamide)-based copolymer hydrogels for potential drug delivery applications

Novel thermo-sensitive N,N-diethylacrylamide (DEAAm) based copolymer hydrogels were prepared via UV-induced free radical bulk polymerisation. UV polymerisation was employed to avoid the use of potentially toxic solvents; solution polymerisation has been the most common means for the preparation of PDEAAm-based hydrogels in the literature to date. The resultant hydrogels were analysed using nuclear magnetic resonance, Fourier transform infrared spectroscopy and modulated differential scanning calorimetry. Parameters such as the crosslinking degree and the nature of the incorporated hydrophilic component, N-vinyl-2-pyrrolidone (NVP) or N,N-dimethylacrylamide (DMAAm) were found to impact hydrogel structure, mechanical properties and swelling kinetics. Pulsatile swelling studies indicated that the hydrogels had thermo-reversible properties which were greatly affected by test temperature, nature of hydrophilic monomer used and crosslinker content. Aminophylline was selected as a model solute for drug loading and release studies by thermal deswelling in HCl buffer (pH 1.4) and phosphate buffer media (pH 6.8). The observed lag time prior to significant drug release from the more crosslinked P(DEAAm-NVP) hydrogels could make them suitable for delayed specific release in the intestine and potential alternatives to layers or membranes in time-specific and site-specific swelling-controlled drug delivery systems.

Physical and Mechanical Properties of Blends Based on Poly (dl-lactide), Poly (l-lactide-glycolide) and Poly (ϵ-caprolactone)

Bioresorbable materials are extensively used for a wide range of biomedical applications. In this study, the common industrial processes of compression moulding and solvent casting were utilised for initial preparation of thin film blends based on Poly (dl-lactide), Poly (l-lactide-glycolide) and Poly (ϵ-caprolactone). Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), phosphate buffered saline adsorption, tensile testing and contact angle measurement were used as a means of investigating the physical and mechanical properties of the blends.

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.