Growth Factor Delivery from Hydrogel Wound Dressings

BioCure has demonstrated the delivery of growth factor from its hydrogel wound dressings. The primary product focus is an active wound dressing for chronic wounds.

:: Rationale

The use of hydrogels for moist wound healing can accelerate healing and is accepted clinical practice for wounds that have low to medium exudate. In addition to their value in maintaining a moist wound environment, hydrogels potentially have the capacity to act as a depot for active agents. The product concept for a chronic wound dressing is a hydrogel that releases growth factor over 2 to 7 days and that can be applied as a spray or as a preformed conformal wound dressing.

:: Technology Description

BioCure's PVA based hydrogels are able to be fabricated with variable backbone chain length, crosslink density, and water content. Varying these parameters can alter both the physical properties and the drug releasing properties of the hydrogel. Release of macromolecules from nelfilcon-based hydrogel is primarily via diffusion and this process can be influenced by changing the effective "pore" size, or mesh size, available for diffusion. Increasing the crosslink density and increasing the solids content can both act to decrease the mesh size and thus decrease the rate of diffusion. Another method that can alter the release rate of macromolecules is use of degradable nelfilcon with tailored degradation time. A range of degradable nelfilcon-based hydrogels has been developed at BioCure. These have degradation times from around 10 days up to 6 weeks and conceivably, protein release could be matched to the degradation rate.

:: Results to Date

Proteins with molecular weights in the range of most growth factors (approximately 14,000 to 25,000 daltons) are released from nelfilcon-based hydrogels following entrapment. In vitro studies have demonstrated that about 50% of the loaded dose of 21,000 Mw model protein can be released from nelfilcon-based hydrogel fabricated with 14,000 molecular weight macromer having about 6 crosslinkers per chain. This can be increased by addition of excipients, like hydrophilic fillers as shown in Figure A.

Figure A. Release of Model Protein from Nelfilcon (open diamonds represent the baseline release and shaded diamonds represent release from hydrogel with a hydrophilic filler incorporated). A critical aspect of protein release is maintenance of bioactivity of the protein during hydrogel fabrication and in vivo exposure. In vitro studies to examine the effect of entrapping PDGF within BioCure hydrogels on bioactivity of PDGF have been conducted.

Figure B shows that PDGF increases the growth of human dermal fibroblasts over 5 day incubation periods (light gray bars) when compared with control media without PDGF (white bars). When a similar concentration of PDGF is loaded into PVA hydrogels with hydrophilic filler, growth rate is similar to that in cells exposed to free PDGF (dark gray bars). This demonstrates that the PDGF is released in an active form up to at least 5 days.

Figure B. Effect of PDGF in PVA on Growth of HDF

Further research and development of this protein delivery technology is planned. Combination of this technology with BioCure's nitric oxide releasing hydrogels could potentially have a synergistic effect on wound healing.

:: Patent Position

Issued patents for the fast crosslinking PVA hydrogel system. Patents pending for use of the PVA hydrogel system for preformed and in situ formed wound dressings.

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