Promoting nerve regeneration requires engineering cellular carriers to physically and biochemical... more Promoting nerve regeneration requires engineering cellular carriers to physically and biochemically support neuronal growth into a long lasting functional tissue. This study systematically evaluated the capacity of a biosynthetic poly(vinyl alcohol) (PVA) hydrogel to support growth and differentiation of co-encapsulated neurons and glia. A significant challenge is to understand the role of the dynamic degradable hydrogel mechanical properties on expression of relevant cellular morphologies and function. It was hypothesised that a carrier with mechanical properties akin to neural tissue will provide glia with conditions to thrive, and that glia in turn will support neuronal survival and development. PVA co-polymerised with biological macromolecules sericin and gelatin (PVA-SG) and with tailored nerve tissue-like mechanical properties were used to encapsulate Schwann cells (SCs) alone and subsequently a co-culture of SCs and neural-like PC12s. SCs were encapsulated within two PVA-SG gel variants with initial compressive moduli of 16 kPa and 2 kPa, spanning a range of reported mechanical properties for neural tissues. Both hydrogels were shown to support cell viability and expression of extracellular matrix proteins, however, SCs grown within the PVA-SG with a higher initial modulus were observed to present with greater physiologically relevant morphologies and increased expression of extracellular matrix proteins. The higher modulus PVA-SG was subsequently shown to support development of neuronal networks when SCs were co-encapsulated with PC12s. The lower modulus hydrogel was unable to support
Summary:This work focuses on the characterisation of ascorbic acid/persulphate initiating system.... more Summary:This work focuses on the characterisation of ascorbic acid/persulphate initiating system. Three different persulphates were used (ammonium, potassium and sodium), and a range of initiator concentrations were tested. Gel time, gel quality, initiator toxicity, and cell survival upon encapsulation were measured. No significant differences were observed between the three types of persulphates. Higher concentrations of the initiators resulted in faster gel times (5min for 0.05wt% initiator) and higher quality gels (less than 20% sol fraction), although the lower initiator concentrations were better in terms of cell growth inhibition and survival upon encapsulation. Overall, this system shows great promise for use in biomedical applications, however there is a need to minimise the initiator concentration to increase cell compatibility while maintaining a high enough concentration for adequate gel formation.
State-of-the-art neurorprostheses rely on stiff metallic electrodes to communicate with neural ti... more State-of-the-art neurorprostheses rely on stiff metallic electrodes to communicate with neural tissues. It was envisioned that a soft, organic electrode coating embedded with functional neural cells will enhance electrode-tissue integration. To enable such a device, it is necessary to produce a cell scaffold with mechanical properties matched to native neural tissue. A degradable poly(vinyl alcohol) (PVA) hydrogel was tailored to have a range of compressive moduli through variation in macromer composition and initiator amount. A regression model was used to predict the amount of initiator required for hydrogel polymerization with nominal macromer content ranging between 5 and 20 wt %. Hydrogels at 5 and 10 wt % were reliably formed but 15 wt % and above were not able to be fabricated due to the light attenuation properties of the initiator ruthenium at increased concentration. Compressive modulus of hydrogels decreased upon incorporation of biomolecules (sericin and gelatin), however, the bulk stiffness spanned the range required to match neural tissue properties (0.04-20kPa). Neuroglia cells, such as Schwann cells survived and grew within the scaffold. The significant finding of this work is that the PVA-tyramine system can be tuned to provide a soft degradable scaffold for neural tissue regeneration while presenting bioactive molecules for cellular expansion.
Heparin-based hydrogels are attractive for controlled growth factor delivery, due to the native a... more Heparin-based hydrogels are attractive for controlled growth factor delivery, due to the native ability of heparin to bind and stabilize growth factors. Basic fibroblast growth factor and vascular endothelial growth factor are heparinbinding growth factors that synergistically enhance angiogenesis. Mild, in situ encapsulation of both basic fibroblast growth factor and vascular endothelial growth factor and subsequent bioactive dual release has not been demonstrated from heparin-crosslinked hydrogels, and the combined long-term delivery of both growth factors from biomaterials is still a major challenge. Both basic fibroblast growth factor and vascular endothelial growth factor were encapsulated in poly(vinyl alcohol)-heparin hydrogels and demonstrated controlled release. A model cell line, BaF32, was used to show bioactivity of heparin and basic fibroblast growth factor released from the gels over multiple days. Released basic fibroblast growth factor promoted higher human umbilical vein endothelial cell outgrowth over 24 h and proliferation for 3 days than the poly(vinyl alcohol)-heparin hydrogels alone. The release of vascular endothelial growth factor from poly(vinyl alcohol)-heparin hydrogels promoted human umbilical vein endothelial cell outgrowth but not significant proliferation. Dual-growth factor release of basic fibroblast growth factor and vascular endothelial growth factor from poly(vinyl alcohol)-heparin hydrogels resulted in a synergistic effect with significantly higher human umbilical vein endothelial cell outgrowth compared to basic fibroblast growth factor or vascular endothelial growth factor alone. Poly(vinyl alcohol)-heparin hydrogels allowed bioactive growth factor encapsulation and provided controlled release of multiple growth factors which is beneficial toward tissue regeneration applications. Poly(vinyl alcohol), heparin, hydrogel, vascular endothelial growth factor, basic fibroblast growth factor Date
A living electrode construct that enables integration of cells within bionic devices has been dev... more A living electrode construct that enables integration of cells within bionic devices has been developed. The layered construct uses a combination of non-degradable conductive hydrogel and degradable biosynthetic hydrogel to support cell encapsulation at device surfaces. In this study, the material system is designed and analyzed to understand the impact of the cell carrying component on electrode characteristics. The cell carrying layer is shown to provide a soft interface that supports extracellular matrix development within the electrode while not significantly reducing the charge transfer characteristics. The living layer was shown to degrade over 21 days with minimal swelling upon implantation.
The extracellular matrix is continually remodelled by the action of various enzymes such as hepar... more The extracellular matrix is continually remodelled by the action of various enzymes such as heparanase, which specifically targets heparan sulfate (HS) and is found in human platelets at high levels. The activity of heparin-containing hydrogels following incubation with platelet extract (PE) was investigated in order to simulate the responses that might occur when the hydrogels, as tissue engineered scaffolds, come in contact with blood products at the site of an injury. The heparanase activity of PE on heparin, used as a model of HS, was confirmed by the decrease in molecular weight. PE treatment diminished heparin's anticoagulation property but increased its FGF-2 signalling activity, suggesting that the PE's heparanase activity cleaves at the 3-O-sulfated glucosamine to produce large fragments that can signal cell receptors. The dual effect observed when poly(vinyl alcohol)/heparin co-hydrogels were incubated with PE supports the hypothesis of platelets having the capacity to limit anticoagulation and thus promote blood clot formation, which may be critical in the process of tissue repair.
Synthetic scaffolds show great promise for use in tissue engineering due to their ability to mimi... more Synthetic scaffolds show great promise for use in tissue engineering due to their ability to mimic some aspects of the extracellular matrix, however, their use has been hindered by the lack of inherent recognition sites that are required for protein and cell interactions. Heparan sulfate (HS), a glycosaminoglycan polysaccharide present in the basement membrane and on the cell surface, binds growth factors and cytokines and enhances the signalling of these ligands by forming complexes with their receptors. This study focuses on the formation of photopolymerised hydrogels derived from methacrylated macromers of poly(vinyl alcohol) (PVA) and heparin, with the aim of imparting the growth factor activation property of heparin to the synthetic scaffolds. It was shown that the methacrylate group attachment on heparin did not result in the fragmentation of heparin molecules, and that the biological activity of the methacrylated heparin was preserved as determined by tests on its anticoagulation properties and ability to signal fibroblast growth factor-2 (FGF-2). The addition of heparin into the PVA hydrogels resulted in an increase in mass swelling ratio from 5.8 for pure PVA to 6.5 and 6.6 for PVA/heparin co-hydrogels of 19/1 and 17.5/2.5 (w/w) compositions, respectively. It is believed that heparin molecules can be added into a synthetic PVA scaffold without adversely affecting the structural and mechanical stability of the PVA scaffold. The tensile moduli of the co-hydrogels remained close to that of PVA hydrogels (61 kPa), even up to 2.5% heparin composition (PVA/hep 17.5/2.5). Finally, the co-hydrogels were found to retain the growth factor signalling activity of heparin at equilibrium.
Conducting hydrogels (CHs) are an emerging technology in the field of medical electrodes and brai... more Conducting hydrogels (CHs) are an emerging technology in the field of medical electrodes and brain-machine interfaces. The greatest challenge to the fabrication of CH electrodes is the hybridization of dissimilar polymers (conductive polymer and hydrogel) to ensure the formation of interpenetrating polymer networks (IPN) required to achieve both soft and electroactive materials. A new hydrogel system is developed that enables tailored placement of covalently immobilized dopant groups within the hydrogel matrix. The role of immobilized dopant in the formation of CH is investigated through covalent linking of sulfonate doping groups to poly(vinyl alcohol) (PVA) macromers. These groups control the electrochemical growth of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and subsequent material properties. The effect of dopant density and interdopant spacing on the physical, electrochemical, and mechanical properties of the resultant CHs is examined. Cytocompatible PVA hydrogels with PEDOT penetration throughout the depth of the electrode are produced. Interdopant spacing is found to be the key factor in the formation of IPNs, with smaller interdopant spacing producing CH electrodes with greater charge storage capacity and lower impedance due to increased PEDOT growth throughout the network. This approach facilitates tailorable, high-performance CH electrodes for next generation, low impedance neuroprosthetic devices. molecules presented by conducting polymers (CPs). By producing composites of CPs and hydrogels, deterioration in mechanical properties and electrochemical stability can be overcome. CH systems have been designed for a variety of applications from stimulating and recording electrodes to electrically controlled drug release devices and biosensors. The most common approach to fabrication of CHs is electrochemical deposition of CP within a preformed hydrogel matrix. However, other approaches such as chemical polymerization of CP within a hydrogel network or simultaneous polymerization of both components have been reported. In all cases, the goal is the same, which is the formation of seamlessly integrated interpenetrating networks (IPNs) of the two dissimilar polymeric components. The formation of IPNs is essential to fully realizing the benefits of creating robust composite materials from CPs and hydrogels. In this study, a novel method of forming IPNs through controlled covalent immobilization of taurine (2-aminoethanesulfonic acid) as a doping pendant group on the polymer backbone. Taurine (TAU) is an amine and sulfur-containing acid which is present in many mammalian tissues and is of low toxicity. By covalently linking taurine onto polymer backbone chains, CHs with a range of controlled dopant distributions can be formed enabling tailoring of physical, mechanical, and electrical properties of these new electrode materials. CH systems in the literature are commonly only partial IPNs or show signs of significant separation of the two polymer components. This is typically the result of electrochemically depositing the CP component within a hydrogel using a mobile dopant. In conventional, electrochemically deposited CP systems the dopant is in solution with the CP monomer. This means the dopant molecules are mobile when the CP film is polymerized and readily available to diffuse to the area where charge balance is required at the newly formed CP backbone. CP films typically have molar dopant ratios (ratio of dopant molecule to CP monomer unit) of between 0.2 and 0.4 meaning one out of every three or four monomer units is associated with a dopant molecule. The CP will nucleate and grow at the surface of the metallic electrode, forming a coherent coating as the electrodeposition proceeds. However, in the context of www.advhealthmat. de
Kinetic aspects of solid state reactive polymers Revision date 2017-01-04 Legend NAV -Not availab... more Kinetic aspects of solid state reactive polymers Revision date 2017-01-04 Legend NAV -Not available 8.2 Exposure controls Personal Protective Equipment Eye/face Protection If splashes are likely to occur: Chemical Goggles. Polychloroprene gloves. Coating thickness 1.1 mm. Level 5 > 240 min breakthrough time. Wear suitable protective clothing. Filter A2 is recommended in cases of prolonged exposure. Eyewash fountains and safety showers must be easily accessible. Handle in accordance with good industrial hygiene and safety practice. No information available. Physical state liquid Color colorless Appearance clear Odor characteristic Odor threshold No information available Property Values Remarks pH No information available No information available Melting / freezing point No information available No information available Boiling point / boiling range No information available No information available Flash point 128 °C / 262.4 °F PMC D93A Evaporation rate No information available No information available Flammability (solid, gas) No information available No information available Flammability Limit in Air Upper flammability limit No information available No information available Lower flammability limit No information available No information available Vapor pressure No information available No information available Vapor density No information available No information available Specific gravity No information available No information available Solubility (water) emulsifiable No information available _____________________________________________________________________________________________ Revision date 2017-01-04 9.2 Other information Bulk Density No information available Explosive properties Can polymerize violently. The substance or mixture is not classified as oxidizing. No information available Molecular weight 420 g/mol Volatile Organic Compound (VOC) content, wt.% No information available Percent Volatile, wt.% < 0.5 % 10. STABILITY AND REACTIVITY 10.1 Reactivity Reactivity Polymerizes readily unless inhibited. Polymerization is highly exothermic and, if not controlled, may be violent. Stable under normal conditions of handling, use and transportation. Periodic air sparging in storage will assist long term stability. May occur if inhibitor is depleted or if exposed to high temperature. This product contains a peroxidation inhibitor. To maintain inhibitor activity, oxygen must not be eliminated from the atmosphere above the product. Avoid radical forming substances (metal-ions, peroxides). Avoid heating. If prolonged excursions above the recommended storage temperature occur, then the rate of inhibitor depletion could accelerate, leading to an increased risk of polymerization. In these circumstances it is recommended that the inhibitor level be checked periodically using ASTM procedure D 3125, and more inhibitor added if depletion is observed. Reaction with reducing agents. Reaction with oxidants. Acids or alkalies. Free radical producing initiators. Primary and Secondary Amines. Hazardous decomposition products Carbon monoxide. Carbon dioxide. Irritating vapors. Solubility in other solvents No information available No information available Partition coefficient: n-octanol/water No information available No information available Autoignition temperature No information available No information available Decomposition temperature No information available No information available Kinematic viscosity 46.00 mm2/s @ 25 °C ASTM D 445-97 Dynamic viscosity No information available No information available Density 1.0220 g/cm 3 _____________________________________________________________________________________________
Increasing demands on neuroprosthetic bioelectrodes have created a need for electrode materials t... more Increasing demands on neuroprosthetic bioelectrodes have created a need for electrode materials that can support the safe and sustainable delivery of electrical stimulation to excitable tissues. Conducting polymers have become a focal point of research into next-generation electrode materials due to their superior electrical properties for charge transfer in biological environments. Perhaps the greatest potential of conducting polymers within neural applications is their ability to accommodate biofunctionality through the incorporation and controlled release of bioactive molecules. Incorporation of neurotrophic factors, cell adhesion molecules and various drug compounds within conducting polymers has been shown to assist in the development of higher quality tissue–electrode interfaces. However, limitations associated with drug loading and the impact of adding biological molecules on mechanical and electrical properties of biofunctionalised conducting polymers restrict their use in medical device applications. This chapter assesses the role of conducting polymers as bioelectrode materials, means of biofunctionalisation and the resultant challenges and limitations. Furthermore, this chapter evaluates the strategies developed to overcome these limitations in the pursuit of the development of high quality neural interfaces.
Journal of the Mechanical Behavior of Biomedical Materials, 2022
Water is a crucial component of bone, affecting the interplay of collagen and minerals and contri... more Water is a crucial component of bone, affecting the interplay of collagen and minerals and contributing to bone's high strength and ductility. Dehydration has been shown to significantly effect osseous mechanical properties; however, studies comparing the effects of various dehydrating environments on fracture toughness of bone are scarce. Accordingly, the crack resistance curve (R-curve) behavior of human and sheep cortical bone was characterized in a bio-bath, in ambient pressure air, and in scanning electron microscopes (SEMs) under three different environmental conditions (water vapor pressure, air pressure, and high-vacuum). The aim of this work was to better understand the impact of test environment on both intrinsic and extrinsic toughening and hence crack initiation toughness, K0 and crack growth resistance, dK/dΔa. Results show significantly lower K0 values for samples that were tested inside SEMs combined with pronounced extrinsic toughening through microcracking and crack path deflections out of the mode I plane. Importantly, all three SEM test environments gave similar results, and thus it does not matter which type of SEM is used. Ex situ testing of hydrated samples revealed similar K0 for both environments but elevated crack growth resistance for testing in ambient air relative to the bio-bath. Our data reveals the experimental difficulties to directly observe microscale crack propagation in cortical bone that resembles the in vivo situation. Ex situ testing immersed in Hanks' Balanced Salt Solution (HBSS) with subsequent crack path analysis, while tedious, is thought to presents the most realistic picture of the in vivo structure-fracture property relations in biological tissue.
Calcium phosphates constitute an important family of biomaterials resembling the part of calcifie... more Calcium phosphates constitute an important family of biomaterials resembling the part of calcified tissues. This study is based on calcium phosphate such as hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 , Hap), fluorapatite (Ca 10 (PO 4 ) 6 F 2 , Fap) and tricalcium phosphate (Ca 3 (PO 4 ) 2 , TCP) phases because their chemical composition is similar to that of bone mineral (Hench
Since the permeation of the inflammatory cytokines into hydrogel scaffolds has been shown to caus... more Since the permeation of the inflammatory cytokines into hydrogel scaffolds has been shown to cause dysfunction of encapsulated cells, appropriate design strategies to circumvent this are essential. In the present work, it was hypothesized that highly crosslinked PVA-fucoidan and PVA-carrageenan hydrogels can control permeation of the trefoil-shaped inflammatory cytokine IL-1β while allowing the permeation of the globular protein albumin. PVA, fucoidan, and carrageenans were functionalized with methacrylate groups and the functionalized polymers were co-crosslinked by UV photopolymerization. The resultant hydrogels were characterized physicochemically and the release of fucoidan and carrageenans was quantified by developing a colorimetric assay, which was validated by XPS analysis. The permeability characteristics of the hydrogels were evaluated using bovine serum albumin (BSA), IgG, and IL-1β. The results demonstrated an increase in hydrogel swelling through the incorporation of the polysaccharides with minimal overall mass loss. The release studies showed hydrogel stability, where the formulations exhibited ~43% retention of fucoidan and ~60-80% retention of carrageenans consistently up to 7 days. The permeation data revealed very low permeation of IgG and IL-1β through the hydrogels, with <1% permeation after 24 h, while allowing >6% permeation of BSA. These data indicate that such hydrogels can be used as the basis for cytokine-protective implantable devices for clinical applications.
Jackfruit mucilage (JM) obtained from the fruit, Artocarpus heterophyllus was melt blended with p... more Jackfruit mucilage (JM) obtained from the fruit, Artocarpus heterophyllus was melt blended with poly(ε‐caprolactone) (PCL). The physical properties of the blends with more than 60 wt% PCL were investigated. Depression in the equilibrium melting temperature () and the presence of extinction rings in the spherulites of PCL in the blends confirmed miscibility of the two components. The carbonyl and the COC groups of PCL and JM were responsible for the interactions as identified by Fourier transform infrared spectroscopy. The thermal stability of PCL decreased marginally in the blends with increasing JM content. The scanning electron microscopy (SEM) images indicated that no phase separation occurred. Porosity and the mechanical strength of the blends decreased with increasing JM content. Blends exposed to porcine pancreatic lipase showed enzymatic degradation of JM but not PCL and SEM images showed holes in the sample indicative of selective degradation of JM. Cell growth inhibition ...
Promoting nerve regeneration requires engineering cellular carriers to physically and biochemical... more Promoting nerve regeneration requires engineering cellular carriers to physically and biochemically support neuronal growth into a long lasting functional tissue. This study systematically evaluated the capacity of a biosynthetic poly(vinyl alcohol) (PVA) hydrogel to support growth and differentiation of co-encapsulated neurons and glia. A significant challenge is to understand the role of the dynamic degradable hydrogel mechanical properties on expression of relevant cellular morphologies and function. It was hypothesised that a carrier with mechanical properties akin to neural tissue will provide glia with conditions to thrive, and that glia in turn will support neuronal survival and development. PVA co-polymerised with biological macromolecules sericin and gelatin (PVA-SG) and with tailored nerve tissue-like mechanical properties were used to encapsulate Schwann cells (SCs) alone and subsequently a co-culture of SCs and neural-like PC12s. SCs were encapsulated within two PVA-SG gel variants with initial compressive moduli of 16 kPa and 2 kPa, spanning a range of reported mechanical properties for neural tissues. Both hydrogels were shown to support cell viability and expression of extracellular matrix proteins, however, SCs grown within the PVA-SG with a higher initial modulus were observed to present with greater physiologically relevant morphologies and increased expression of extracellular matrix proteins. The higher modulus PVA-SG was subsequently shown to support development of neuronal networks when SCs were co-encapsulated with PC12s. The lower modulus hydrogel was unable to support
Summary:This work focuses on the characterisation of ascorbic acid/persulphate initiating system.... more Summary:This work focuses on the characterisation of ascorbic acid/persulphate initiating system. Three different persulphates were used (ammonium, potassium and sodium), and a range of initiator concentrations were tested. Gel time, gel quality, initiator toxicity, and cell survival upon encapsulation were measured. No significant differences were observed between the three types of persulphates. Higher concentrations of the initiators resulted in faster gel times (5min for 0.05wt% initiator) and higher quality gels (less than 20% sol fraction), although the lower initiator concentrations were better in terms of cell growth inhibition and survival upon encapsulation. Overall, this system shows great promise for use in biomedical applications, however there is a need to minimise the initiator concentration to increase cell compatibility while maintaining a high enough concentration for adequate gel formation.
State-of-the-art neurorprostheses rely on stiff metallic electrodes to communicate with neural ti... more State-of-the-art neurorprostheses rely on stiff metallic electrodes to communicate with neural tissues. It was envisioned that a soft, organic electrode coating embedded with functional neural cells will enhance electrode-tissue integration. To enable such a device, it is necessary to produce a cell scaffold with mechanical properties matched to native neural tissue. A degradable poly(vinyl alcohol) (PVA) hydrogel was tailored to have a range of compressive moduli through variation in macromer composition and initiator amount. A regression model was used to predict the amount of initiator required for hydrogel polymerization with nominal macromer content ranging between 5 and 20 wt %. Hydrogels at 5 and 10 wt % were reliably formed but 15 wt % and above were not able to be fabricated due to the light attenuation properties of the initiator ruthenium at increased concentration. Compressive modulus of hydrogels decreased upon incorporation of biomolecules (sericin and gelatin), however, the bulk stiffness spanned the range required to match neural tissue properties (0.04-20kPa). Neuroglia cells, such as Schwann cells survived and grew within the scaffold. The significant finding of this work is that the PVA-tyramine system can be tuned to provide a soft degradable scaffold for neural tissue regeneration while presenting bioactive molecules for cellular expansion.
Heparin-based hydrogels are attractive for controlled growth factor delivery, due to the native a... more Heparin-based hydrogels are attractive for controlled growth factor delivery, due to the native ability of heparin to bind and stabilize growth factors. Basic fibroblast growth factor and vascular endothelial growth factor are heparinbinding growth factors that synergistically enhance angiogenesis. Mild, in situ encapsulation of both basic fibroblast growth factor and vascular endothelial growth factor and subsequent bioactive dual release has not been demonstrated from heparin-crosslinked hydrogels, and the combined long-term delivery of both growth factors from biomaterials is still a major challenge. Both basic fibroblast growth factor and vascular endothelial growth factor were encapsulated in poly(vinyl alcohol)-heparin hydrogels and demonstrated controlled release. A model cell line, BaF32, was used to show bioactivity of heparin and basic fibroblast growth factor released from the gels over multiple days. Released basic fibroblast growth factor promoted higher human umbilical vein endothelial cell outgrowth over 24 h and proliferation for 3 days than the poly(vinyl alcohol)-heparin hydrogels alone. The release of vascular endothelial growth factor from poly(vinyl alcohol)-heparin hydrogels promoted human umbilical vein endothelial cell outgrowth but not significant proliferation. Dual-growth factor release of basic fibroblast growth factor and vascular endothelial growth factor from poly(vinyl alcohol)-heparin hydrogels resulted in a synergistic effect with significantly higher human umbilical vein endothelial cell outgrowth compared to basic fibroblast growth factor or vascular endothelial growth factor alone. Poly(vinyl alcohol)-heparin hydrogels allowed bioactive growth factor encapsulation and provided controlled release of multiple growth factors which is beneficial toward tissue regeneration applications. Poly(vinyl alcohol), heparin, hydrogel, vascular endothelial growth factor, basic fibroblast growth factor Date
A living electrode construct that enables integration of cells within bionic devices has been dev... more A living electrode construct that enables integration of cells within bionic devices has been developed. The layered construct uses a combination of non-degradable conductive hydrogel and degradable biosynthetic hydrogel to support cell encapsulation at device surfaces. In this study, the material system is designed and analyzed to understand the impact of the cell carrying component on electrode characteristics. The cell carrying layer is shown to provide a soft interface that supports extracellular matrix development within the electrode while not significantly reducing the charge transfer characteristics. The living layer was shown to degrade over 21 days with minimal swelling upon implantation.
The extracellular matrix is continually remodelled by the action of various enzymes such as hepar... more The extracellular matrix is continually remodelled by the action of various enzymes such as heparanase, which specifically targets heparan sulfate (HS) and is found in human platelets at high levels. The activity of heparin-containing hydrogels following incubation with platelet extract (PE) was investigated in order to simulate the responses that might occur when the hydrogels, as tissue engineered scaffolds, come in contact with blood products at the site of an injury. The heparanase activity of PE on heparin, used as a model of HS, was confirmed by the decrease in molecular weight. PE treatment diminished heparin's anticoagulation property but increased its FGF-2 signalling activity, suggesting that the PE's heparanase activity cleaves at the 3-O-sulfated glucosamine to produce large fragments that can signal cell receptors. The dual effect observed when poly(vinyl alcohol)/heparin co-hydrogels were incubated with PE supports the hypothesis of platelets having the capacity to limit anticoagulation and thus promote blood clot formation, which may be critical in the process of tissue repair.
Synthetic scaffolds show great promise for use in tissue engineering due to their ability to mimi... more Synthetic scaffolds show great promise for use in tissue engineering due to their ability to mimic some aspects of the extracellular matrix, however, their use has been hindered by the lack of inherent recognition sites that are required for protein and cell interactions. Heparan sulfate (HS), a glycosaminoglycan polysaccharide present in the basement membrane and on the cell surface, binds growth factors and cytokines and enhances the signalling of these ligands by forming complexes with their receptors. This study focuses on the formation of photopolymerised hydrogels derived from methacrylated macromers of poly(vinyl alcohol) (PVA) and heparin, with the aim of imparting the growth factor activation property of heparin to the synthetic scaffolds. It was shown that the methacrylate group attachment on heparin did not result in the fragmentation of heparin molecules, and that the biological activity of the methacrylated heparin was preserved as determined by tests on its anticoagulation properties and ability to signal fibroblast growth factor-2 (FGF-2). The addition of heparin into the PVA hydrogels resulted in an increase in mass swelling ratio from 5.8 for pure PVA to 6.5 and 6.6 for PVA/heparin co-hydrogels of 19/1 and 17.5/2.5 (w/w) compositions, respectively. It is believed that heparin molecules can be added into a synthetic PVA scaffold without adversely affecting the structural and mechanical stability of the PVA scaffold. The tensile moduli of the co-hydrogels remained close to that of PVA hydrogels (61 kPa), even up to 2.5% heparin composition (PVA/hep 17.5/2.5). Finally, the co-hydrogels were found to retain the growth factor signalling activity of heparin at equilibrium.
Conducting hydrogels (CHs) are an emerging technology in the field of medical electrodes and brai... more Conducting hydrogels (CHs) are an emerging technology in the field of medical electrodes and brain-machine interfaces. The greatest challenge to the fabrication of CH electrodes is the hybridization of dissimilar polymers (conductive polymer and hydrogel) to ensure the formation of interpenetrating polymer networks (IPN) required to achieve both soft and electroactive materials. A new hydrogel system is developed that enables tailored placement of covalently immobilized dopant groups within the hydrogel matrix. The role of immobilized dopant in the formation of CH is investigated through covalent linking of sulfonate doping groups to poly(vinyl alcohol) (PVA) macromers. These groups control the electrochemical growth of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and subsequent material properties. The effect of dopant density and interdopant spacing on the physical, electrochemical, and mechanical properties of the resultant CHs is examined. Cytocompatible PVA hydrogels with PEDOT penetration throughout the depth of the electrode are produced. Interdopant spacing is found to be the key factor in the formation of IPNs, with smaller interdopant spacing producing CH electrodes with greater charge storage capacity and lower impedance due to increased PEDOT growth throughout the network. This approach facilitates tailorable, high-performance CH electrodes for next generation, low impedance neuroprosthetic devices. molecules presented by conducting polymers (CPs). By producing composites of CPs and hydrogels, deterioration in mechanical properties and electrochemical stability can be overcome. CH systems have been designed for a variety of applications from stimulating and recording electrodes to electrically controlled drug release devices and biosensors. The most common approach to fabrication of CHs is electrochemical deposition of CP within a preformed hydrogel matrix. However, other approaches such as chemical polymerization of CP within a hydrogel network or simultaneous polymerization of both components have been reported. In all cases, the goal is the same, which is the formation of seamlessly integrated interpenetrating networks (IPNs) of the two dissimilar polymeric components. The formation of IPNs is essential to fully realizing the benefits of creating robust composite materials from CPs and hydrogels. In this study, a novel method of forming IPNs through controlled covalent immobilization of taurine (2-aminoethanesulfonic acid) as a doping pendant group on the polymer backbone. Taurine (TAU) is an amine and sulfur-containing acid which is present in many mammalian tissues and is of low toxicity. By covalently linking taurine onto polymer backbone chains, CHs with a range of controlled dopant distributions can be formed enabling tailoring of physical, mechanical, and electrical properties of these new electrode materials. CH systems in the literature are commonly only partial IPNs or show signs of significant separation of the two polymer components. This is typically the result of electrochemically depositing the CP component within a hydrogel using a mobile dopant. In conventional, electrochemically deposited CP systems the dopant is in solution with the CP monomer. This means the dopant molecules are mobile when the CP film is polymerized and readily available to diffuse to the area where charge balance is required at the newly formed CP backbone. CP films typically have molar dopant ratios (ratio of dopant molecule to CP monomer unit) of between 0.2 and 0.4 meaning one out of every three or four monomer units is associated with a dopant molecule. The CP will nucleate and grow at the surface of the metallic electrode, forming a coherent coating as the electrodeposition proceeds. However, in the context of www.advhealthmat. de
Kinetic aspects of solid state reactive polymers Revision date 2017-01-04 Legend NAV -Not availab... more Kinetic aspects of solid state reactive polymers Revision date 2017-01-04 Legend NAV -Not available 8.2 Exposure controls Personal Protective Equipment Eye/face Protection If splashes are likely to occur: Chemical Goggles. Polychloroprene gloves. Coating thickness 1.1 mm. Level 5 > 240 min breakthrough time. Wear suitable protective clothing. Filter A2 is recommended in cases of prolonged exposure. Eyewash fountains and safety showers must be easily accessible. Handle in accordance with good industrial hygiene and safety practice. No information available. Physical state liquid Color colorless Appearance clear Odor characteristic Odor threshold No information available Property Values Remarks pH No information available No information available Melting / freezing point No information available No information available Boiling point / boiling range No information available No information available Flash point 128 °C / 262.4 °F PMC D93A Evaporation rate No information available No information available Flammability (solid, gas) No information available No information available Flammability Limit in Air Upper flammability limit No information available No information available Lower flammability limit No information available No information available Vapor pressure No information available No information available Vapor density No information available No information available Specific gravity No information available No information available Solubility (water) emulsifiable No information available _____________________________________________________________________________________________ Revision date 2017-01-04 9.2 Other information Bulk Density No information available Explosive properties Can polymerize violently. The substance or mixture is not classified as oxidizing. No information available Molecular weight 420 g/mol Volatile Organic Compound (VOC) content, wt.% No information available Percent Volatile, wt.% < 0.5 % 10. STABILITY AND REACTIVITY 10.1 Reactivity Reactivity Polymerizes readily unless inhibited. Polymerization is highly exothermic and, if not controlled, may be violent. Stable under normal conditions of handling, use and transportation. Periodic air sparging in storage will assist long term stability. May occur if inhibitor is depleted or if exposed to high temperature. This product contains a peroxidation inhibitor. To maintain inhibitor activity, oxygen must not be eliminated from the atmosphere above the product. Avoid radical forming substances (metal-ions, peroxides). Avoid heating. If prolonged excursions above the recommended storage temperature occur, then the rate of inhibitor depletion could accelerate, leading to an increased risk of polymerization. In these circumstances it is recommended that the inhibitor level be checked periodically using ASTM procedure D 3125, and more inhibitor added if depletion is observed. Reaction with reducing agents. Reaction with oxidants. Acids or alkalies. Free radical producing initiators. Primary and Secondary Amines. Hazardous decomposition products Carbon monoxide. Carbon dioxide. Irritating vapors. Solubility in other solvents No information available No information available Partition coefficient: n-octanol/water No information available No information available Autoignition temperature No information available No information available Decomposition temperature No information available No information available Kinematic viscosity 46.00 mm2/s @ 25 °C ASTM D 445-97 Dynamic viscosity No information available No information available Density 1.0220 g/cm 3 _____________________________________________________________________________________________
Increasing demands on neuroprosthetic bioelectrodes have created a need for electrode materials t... more Increasing demands on neuroprosthetic bioelectrodes have created a need for electrode materials that can support the safe and sustainable delivery of electrical stimulation to excitable tissues. Conducting polymers have become a focal point of research into next-generation electrode materials due to their superior electrical properties for charge transfer in biological environments. Perhaps the greatest potential of conducting polymers within neural applications is their ability to accommodate biofunctionality through the incorporation and controlled release of bioactive molecules. Incorporation of neurotrophic factors, cell adhesion molecules and various drug compounds within conducting polymers has been shown to assist in the development of higher quality tissue–electrode interfaces. However, limitations associated with drug loading and the impact of adding biological molecules on mechanical and electrical properties of biofunctionalised conducting polymers restrict their use in medical device applications. This chapter assesses the role of conducting polymers as bioelectrode materials, means of biofunctionalisation and the resultant challenges and limitations. Furthermore, this chapter evaluates the strategies developed to overcome these limitations in the pursuit of the development of high quality neural interfaces.
Journal of the Mechanical Behavior of Biomedical Materials, 2022
Water is a crucial component of bone, affecting the interplay of collagen and minerals and contri... more Water is a crucial component of bone, affecting the interplay of collagen and minerals and contributing to bone's high strength and ductility. Dehydration has been shown to significantly effect osseous mechanical properties; however, studies comparing the effects of various dehydrating environments on fracture toughness of bone are scarce. Accordingly, the crack resistance curve (R-curve) behavior of human and sheep cortical bone was characterized in a bio-bath, in ambient pressure air, and in scanning electron microscopes (SEMs) under three different environmental conditions (water vapor pressure, air pressure, and high-vacuum). The aim of this work was to better understand the impact of test environment on both intrinsic and extrinsic toughening and hence crack initiation toughness, K0 and crack growth resistance, dK/dΔa. Results show significantly lower K0 values for samples that were tested inside SEMs combined with pronounced extrinsic toughening through microcracking and crack path deflections out of the mode I plane. Importantly, all three SEM test environments gave similar results, and thus it does not matter which type of SEM is used. Ex situ testing of hydrated samples revealed similar K0 for both environments but elevated crack growth resistance for testing in ambient air relative to the bio-bath. Our data reveals the experimental difficulties to directly observe microscale crack propagation in cortical bone that resembles the in vivo situation. Ex situ testing immersed in Hanks' Balanced Salt Solution (HBSS) with subsequent crack path analysis, while tedious, is thought to presents the most realistic picture of the in vivo structure-fracture property relations in biological tissue.
Calcium phosphates constitute an important family of biomaterials resembling the part of calcifie... more Calcium phosphates constitute an important family of biomaterials resembling the part of calcified tissues. This study is based on calcium phosphate such as hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 , Hap), fluorapatite (Ca 10 (PO 4 ) 6 F 2 , Fap) and tricalcium phosphate (Ca 3 (PO 4 ) 2 , TCP) phases because their chemical composition is similar to that of bone mineral (Hench
Since the permeation of the inflammatory cytokines into hydrogel scaffolds has been shown to caus... more Since the permeation of the inflammatory cytokines into hydrogel scaffolds has been shown to cause dysfunction of encapsulated cells, appropriate design strategies to circumvent this are essential. In the present work, it was hypothesized that highly crosslinked PVA-fucoidan and PVA-carrageenan hydrogels can control permeation of the trefoil-shaped inflammatory cytokine IL-1β while allowing the permeation of the globular protein albumin. PVA, fucoidan, and carrageenans were functionalized with methacrylate groups and the functionalized polymers were co-crosslinked by UV photopolymerization. The resultant hydrogels were characterized physicochemically and the release of fucoidan and carrageenans was quantified by developing a colorimetric assay, which was validated by XPS analysis. The permeability characteristics of the hydrogels were evaluated using bovine serum albumin (BSA), IgG, and IL-1β. The results demonstrated an increase in hydrogel swelling through the incorporation of the polysaccharides with minimal overall mass loss. The release studies showed hydrogel stability, where the formulations exhibited ~43% retention of fucoidan and ~60-80% retention of carrageenans consistently up to 7 days. The permeation data revealed very low permeation of IgG and IL-1β through the hydrogels, with <1% permeation after 24 h, while allowing >6% permeation of BSA. These data indicate that such hydrogels can be used as the basis for cytokine-protective implantable devices for clinical applications.
Jackfruit mucilage (JM) obtained from the fruit, Artocarpus heterophyllus was melt blended with p... more Jackfruit mucilage (JM) obtained from the fruit, Artocarpus heterophyllus was melt blended with poly(ε‐caprolactone) (PCL). The physical properties of the blends with more than 60 wt% PCL were investigated. Depression in the equilibrium melting temperature () and the presence of extinction rings in the spherulites of PCL in the blends confirmed miscibility of the two components. The carbonyl and the COC groups of PCL and JM were responsible for the interactions as identified by Fourier transform infrared spectroscopy. The thermal stability of PCL decreased marginally in the blends with increasing JM content. The scanning electron microscopy (SEM) images indicated that no phase separation occurred. Porosity and the mechanical strength of the blends decreased with increasing JM content. Blends exposed to porcine pancreatic lipase showed enzymatic degradation of JM but not PCL and SEM images showed holes in the sample indicative of selective degradation of JM. Cell growth inhibition ...
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