Solid emulsion gel as a vehicle for delivery of polyunsaturated fatty acids: implications for tissue repair, dermal angiogenesis and wound healing.

The paper describes preparation and biological characterization of the solid hybrid biomaterial that was designed for cell-targeted lipid delivery in healing tissues. The material referred to as 'solid emulsion gel' combines a protein-stabilized lipid emulsion and a hydrogel structure in a single compartment. The potential of the omega-3 (n-3)-fatty acids rich solid emulsion gel for tissue repair applications was investigated at the macro-, micro-, molecular and gene expression levels, using human fibroblasts and endothelial cells and a porcine model of full-thickness wounds. Being non-cytotoxic in vitro and in vivo, the biomaterial was found to affect cell metabolism, modulate expression of certain genes, stimulate early angiogenesis and promote wound repair in vivo. The neovascular response in vivo was correlated with upregulated expression of the genes involved in lipid transport (e.g. adipophilin), anti-apoptosis (e.g. heat shock proteins, haem oxygenase 1) and angiogenesis (vascular endothelial growth factor, placental growth factor). Collectively, the results of this study provide first evidence that the angiogenic response provided by solid emulsion gel-mediated delivery of n-3 fatty acids is an alternative to the topical administration of exogenous growth factors or gene therapy, and can be advantageously used for the stimulation of tissue repair in complex wounds.

Mechanical and microstructural properties of hybrid poly(ethylene glycol)-soy protein hydrogels for wound dressing applications.

Biomimetic hydrogel made of poly(ethylene glycol) and soy protein with a water content of 96% has been developed for moist wound dressing applications. In this study, such hybrid hydrogels were investigated by both tensile and unconfined compression measurements in order to understand the relationships between structural parameters of the network, its mechanical properties and protein absorption in vitro. Elastic moduli were found to vary from 1 to 17 kPa depending on the composition, while the Poisson's ratio (approximately 0.18) and deformation at break (approximately 300%) showed no dependence on this parameter. Further calculations yielded the crosslinking concentration, the average molecular weight between crosslinks (M(C)) and the mesh size. The results show that reactions between PEG and protein create polymeric chains comprising molecules of PEG and protein fragments between crosslinks. M(C) is three times higher than that expected for a "theoretical network." On the basis of this data, we propose a model for the 3D network of the hydrogel, which is found to be useful for understanding drug release properties and biomedical potential of the studied material.

Inflammatory inert poly(ethylene glycol)--protein wound dressing improves healing responses in partial- and full-thickness wounds.

In this study, a novel soft hydrogel system based on the poly(ethylene glycol)-protein conjugates was evaluated as an occlusive wound dressing material. The hydrogel material, referred by the name of BioAquacare, contains up to 96% of the liquid and is formulated with phosphate-buffered saline and safe preservative to control bacterial load in the open wounds. Performance of the BioAquacare as a wound dressing material was assessed in partial- and full-thickness wounds in pigs. Wound analysis comprised macroscopic determination of the wound size, histological examination of the healing tissues and biochemical characterisation of wound exudates. The wounds treated with BioAquacare healed without any signs of inflammation, skin irritation, oedema or erythema. Cellular composition of the reepithelialised wounds was very similar to that of the normal skin, with a well-developed stratum corneum and epithelial layer. It was observed that BioAquacare plays the role of a liquid compartment, which provides pronounced hydration effect and helps maintain a natural moist environment of the healing tissues. BioAquacare showed relatively low protein-absorbing activity, absorbing predominantly low-molecular-weight molecules, including interleukin (IL)-1beta, IL-6, transforming growth factor-beta1 and products of haemoglobin degradation. It is concluded that application of the moist BioAquacare dressing promotes fast reepithelialisation by creating favourable environment for keratinocytes proliferation and it also reduces scarring. The results show that BioAquacare can be considered as a safe, biocompatible and inflammatory inert wound dressing material.

Structure-property relationships in poly(ethylene glycol)-protein hydrogel systems made from various proteins.

A series of poly(ethylene glycol)-protein hydrogels were synthesized with different proteins, and the resultant structures were characterized in terms of swelling behavior and mechanical, optical, and drug release properties. Irrespectively of the protein involved in polymerization with poly(ethylene glycol), all studied systems were found to be loosely cross-linked networks, where both polymer and protein are completely solvated, enabling as high as 96% water content. Changes in the apparent transparency of the hydrogels synthesized with different proteins were attributed to the ability of the protein component to self-associate via hydrophobic interactions. The polyelectrolyte nature of the protein component governs the pH responsiveness of the network, which manifested itself in a pH-dependent mechanism of swelling and drug release. It was demonstrated that there is great opportunity to modulate the final characteristics of the hydrogel system to fit the need of specific biomedical application.