Poly(vinyl alcohol) and heparin hydrogels: synthesis, structure and presentation of signalling molecules for growth factor activation

The design of scaffold materials that could be used to assist tissue regeneration has been based on the extracellular matrix (ECM), in structure and in the presentation of molecular cues. Synthetic hydrogels resemble the ECM with their structure, high water content, and elasticity, but they lack bioactivity and recognition. Therefore, the incorporation of biomolecules into synthetic hydrogels is a growing current area of research. Heparan sulfate (HS), a glycosaminoglycan present in basement membrane, has been known to bind and signal various ECM proteins. Sustained presentation of biomolecules like HS could be achieved by covalent linking to scaffolds; however it poses a challenge on the preservation and expression of the biomolecules’ activity after incorporation. Biosynthetic hydrogels derived from heparin (a model for HS) and poly(vinyl alcohol) (PVA) were formed by photopolymerisation. PVA and heparin were both functionalised with photopolymerisable methacrylate groups prior to crosslinking, and the effect of this modification on heparin was examined. PVA/heparin co-hydrogels were made with varying compositions and assessed in terms of their structure, strength and growth factor presentation. The activity of the co-hydrogels following incubation with platelet extract (PE) was also studied, to simulate responses that might occur when the hydrogels, as tissue engineered scaffolds, come in contact with blood products. Heparin remained structurally intact and biologically active following methacrylate modification and UV exposure. The addition of up to 2.5 wt% of heparin increased the hydrogel swelling capacity without compromising the strength of the resulting hydrogel network. The specific FGF-2-signalling activity of heparin in the PVA/heparin co-hydrogels was demonstrated, with results indicating that co-hydrogels may be formulated with a minimal amount of heparin (≥0.05 wt%), thus limiting any effects on structural integrity. PE treatment of the hydrogel-bound heparin diminished its anticoagulation properties but increased the FGF-2 signalling, suggesting the heparanase activity in PE cleave at the antithrombin binding site to yield fragments that can signal cell receptors. This work has demonstrated the formation of biosynthetic co-hydrogels, capable of presenting growth factors to cells, and provides a novel insight on the molecular activation of heparin-based hydrogels upon enzymatic degradation

Organic electrode coatings for next-generation neural interfaces

Traditional neuronal interfaces utilize metallic electrodes which in recent years have reached a plateau in terms of the ability to provide safe stimulation at high resolution or rather with high densities of microelectrodes with improved spatial selectivity. To achieve higher resolution it has become clear that reducing the size of electrodes is required to enable higher electrode counts from the implant device. The limitations of interfacing electrodes including low charge injection limits, mechanical mismatch and foreign body response can be addressed through the use of organic electrode coatings which typically provide a softer, more roughened surface to enable both improved charge transfer and lower mechanical mismatch with neural tissue. Coating electrodes with conductive polymers or carbon nanotubes offers a substantial increase in charge transfer area compared to conventional platinum electrodes. These organic conductors provide safe electrical stimulation of tissue while avoiding undesirable chemical reactions and cell damage. However, the mechanical properties of conductive polymers are not ideal, as they are quite brittle. Hydrogel polymers present a versatile coating option for electrodes as they can be chemically modified to provide a soft and conductive scaffold. However, the in vivo chronic inflammatory response of these conductive hydrogels remains unknown. A more recent approach proposes tissue engineering the electrode interface through the use of encapsulated neurons within hydrogel coatings. This approach may provide a method for activating tissue at the cellular scale, however, several technological challenges must be addressed to demonstrate feasibility of this innovative idea. The review focuses on the various organic coatings which have been investigated to improve neural interface electrodes

Effect of poly(vinyl alcohol) macromer chemistry and chain interactions on hydrogel mechanical properties

Poly (vinyl alcohol) (PVA) is a versatile polymer that when modified with functional groups can be polymerized to produce hydrogels with a range of mechanical properties. In this study, PVA was modified with pendent acrylamide groups and crosslinked via photopolymerisation. The swelling behavior and tensile properties of the resulting hydrogels were studied as a function of percent macromer at the time of polymerization, functional group density, backbone molecular weight, and percent hydrolysis of the PVA. Percent macromer had the strongest influence, with tensile modulus increasing in direct proportion to increasing percent macromer. Changing the functional group density of the macromers as well as changing the molecular weight of the PVA backbone significantly impacted the swelling and mechanical behavior. Although percent hydrolysis of the PVA backbone resulted only in slight variations in the network, it did prove to be a significant variable. However, it was also found that the tensile modulus was directly related to the amount of polymer in the hydrogel. Rheological studies demonstrated that by increasing the number of chain interactions in solution (i.e., increasing the percent macromer, etc.) the resulting network produced was more interconnected and thus stronger. Overall, it was found that hydrogels produced from PVA macromers that had larger molecular weights and more functional groups per PVA chain and were less hydrophilic and formulated into higher percent macromer solutions were stronger, stiffer materials

Poly(vinyl ester) star polymers via xanthate-mediated living radical polymerization: From poly(vinyl alcohol) to glycopolymer stars

PolyCvinyl ester) stars have been synthesized via different macromolecular design via interchange of xanthate (MADIX)/reversible addition-fragmentation chain transfer (RAFT) polymerization methodologies. Two approaches were investigated. The first method involved attaching the xanthate functionality to the core via a nonfragmenting covalent bond (Z-group approach). The second approach involved attaching the xanthate functionality to the core via a fragmenting covalent bond (R-group approach). The R-group approach yielded well-defined poly(vinyl acetate), poly(vinyl pivalate), and poly-(vinyl neodecanoate) stars with narrow polydispersities (PDI ≤ 1.4). In contrast, the molecular weight distributions of poly(vinyl acetate) stars prepared using the Z-approach tended to broaden at moderate to high conversions. We attribute this broadening to steric congestion around the xanthate functionality, restricting the access of monomer to the C=S bonds. The R-group approach was also found to be superior for preparing precursor stars suitable for hydrolysis to poly(vinyl alcohol). Hydrolysis of stars generated by the Z-group approach resulted in destruction of the architecture, as the process also cleaved the xanthate linkage at the nexus of the arms and core. Preliminary experiments on using the R-group approach to mediate the star-polymerization of vinyl-functional glycomonomers demonstrated the possibility of generating complex glycopolymer architectures. However, some significant problems were observed, and this synthetic approach requires further optimization. © 2005 American Chemical Society