Poly(Vinyl Alcohol) Cryogel Membranes Loaded with Resveratrol as Potential Active Wound Dressings.

Hydrogel wound dressings are highly effective in the therapy of wounds. Yet, most of them do not contain any active ingredient that could accelerate healing. The aim of this study was to prepare hydrophilic active dressings loaded with an anti-inflammatory compound - trans-resveratrol (RSV) of hydrophobic properties. A special attention was paid to select such a technological strategy that could both reduce the risk of irritation at the application site and ensure the homogeneity of the final hydrogel. RSV dissolved in Labrasol was combined with an aqueous sol of poly(vinyl) alcohol (PVA), containing propylene glycol (PG) as a plasticizer. This sol was transformed into a gel under six consecutive cycles of freezing (-80 °C) and thawing (RT). White, uniform and elastic membranes were successfully produced. Their critical features, namely microstructure, mechanical properties, water uptake and RSV release were studied using SEM, DSC, MRI, texture analyser and Franz-diffusion cells. The cryogels made of 8 % of PVA showed optimal tensile strength (0.22 MPa) and elasticity (0.082 MPa). The application of MRI enabled to elucidate mass transport related phenomena in this complex system at the molecular (detection of PG, confinement effects related to pore size) as well as at the macro level (swelling). The controlled release of RSV from membranes was observed for 48 h with mean dissolution time of 18 h and dissolution efficiency of 35 %. All in all, these cryogels could be considered as a promising new active wound dressings.

Cryogel scaffolds for regionally constrained delivery of lysophosphatidylcholine to central nervous system slice cultures: A model of focal demyelination for multiple sclerosis research.

The pathology of multiple sclerosis (MS) is typified by focal demyelinated areas of the brain and spinal cord, which results in axonal degeneration and atrophy. Although the field has made much progress in developing immunomodulatory therapies to reduce the occurrence of these focal lesions, there is a conspicuous lack of licensed effective therapies to reduce axonal degeneration or promote repair. Remyelination, carried out by oligodendrocytes, does occur in MS, and is protective against axonal degeneration. Unfortunately, remyelination is not very efficient, and ultimately fails and so there is a research focus to generate new therapeutics to enhance remyelination leading to neuroprotection. To develop these therapies, we need preclinical models that well reflect remyelination in MS. We have previously characterized an ex vivo model that uses lysophosphatidylcholine (LPC) to cause acute and global demyelination of tissue slices, followed by spontaneous remyelination, which has been widely used as a surrogate for in vivo rodent models of demyelination. However, this ex vivo model lacks the focal demyelinated lesions seen in MS, surrounded by normal tissue from which the repairing oligodendrocytes are derived. Therefore, to improve the model, we have developed and characterized small macroporous cryogel scaffolds for controlled/regional delivery of LPC with diameters of either 0.5, 1 or 2 mm. Placement of LPC loaded scaffolds adjacent to ex vivo cultured mouse brain and spinal cord slices induced focal areas of demyelination in proximity to the scaffold. To the best of our knowledge, this is the first such report of spatial mimicry of the in vivo condition in ex vivo tissue culture. This will allow not only the investigation into focal lesions, but also provides a better platform technology with which to test remyelination-promoting therapeutics. STATEMENT OF SIGNIFICANCE: This manuscript is the first report of using macroporous hydrogels (cryogels) as a research tool for lysophosphatidylcholine (LPC) delivery, in order to create an ex vivo model of focal demyelination in the brain and spinal cord, which is of great relevance to multiple sclerosis research. Here, we transform an existing ex vivo model of demyelination by delivering LPC to focal regions of brain and spinal cord slice cultures. We have developed an easy-to-handle cylindrical and macroporous PEG-based sponge-like scaffold material (cryogel) that can deliver LPC only to a small area of the slice. Such cryogels are ideal as a delivery system in this culture model as they exhibit a soft but robust nature, with high mechanical deformability in their dry and swollen state, with no need to stay permanently hydrated. In addition, the synthesis of these cryogels is simple and easy to reproduce via photochemical cryopolymerisation using a PEG-diacrylate monomer and a photoinitiator, which are both commercially available. This more accurate model of demyelination will not only allow researchers to gain a better understanding of the CNS remyelination process in diseases such as MS, but also provides a platform technology, which could be utilized to screen and test pro-remyelination compounds which may help to find new therapeutics for progressive MS.