Solid emulsion gel as a vehicle for delivery of polyunsaturated fatty acids: implications for tissue repair, dermal angiogenesis and wound healing
Shingel, K., Faure, M.P., Azoulay, L., Roberge C., and Deckelbaum, R. Solid emulsion gel as a vehicle for delivery of polyunsaturated fatty acids: implications for tissue repair, dermal angiogenesis and wound healing. J Tissue Eng Regen Med 2008; 2: 383–393.
Summary: Wound healing from complex topical injuries such as ulcers or burns is a major part of regenerative medicine today. There are, however, a very limited number of dressings that actively promote tissue regeneration. When tissue is damaged, some of the main factors involved with the slow rate of healing include ischemia, poor nutrient diffusion to the cells, and a significant reduction in the levels of polyunsaturated fatty acids due to the destruction of cell membranes. This last factor, the polyunsaturated fatty acids (PUFA), is an important part of cell membranes and is required for anabolism in cell and tissue reconstruction. In this paper, Shingel et al. hypothesized that a solid emulsion gel (SEG) combined with PUFA would help bolster the PUFA levels in the tissue, thereby improving rates of tissue repair.
The SEG created in this paper was a hybrid material of protein stabilized lipid emulsion and hydrogel combined in a single compartment. This oil and water combination may be essential since water alone as part of a moist environment has shown to prove beneficial to tissue regeneration. Different SEG were created using olive oil (OO) and fish oil (FO) then applied to pigs as an in vivo test. Wounds were created using a 25mm biopsy punch and the treatments of SEG-OO, SEG-FO, dry gauze, BioAquacareTM were applied. Dressings were changed every two days until the wound had fully closed. The rate of healing was measured as a percentage of wound area remaining from the initial conditions.
The researchers found that the n3-fatty acids found in fish oil such as DHA and EPA had a satistically significant effect on rate of tissue repair when compared to the SEG with olive oil. The delivery of these specific n3-fatty acids to the tissue affected fibroblast and endothelial cell division/repair, and promoted early angiogenesis since newly formed capillaries were visible after four days and persisted until wound closure. Through differential gene expression analysis in vitro, wound repair in the SEG-FO treatment was correlated to an up-regulation of genes involved with lipid transport (adipophilin), anti-apoptosis (heat shock protein, haem oxygenase 1), and angiogenesis (vascular endothelial growth factor). Up-regulation was determined as any gene with a ratio of over 2 between treatment and control.
Significance: Studies in the past have been conducted using free form PUFA applied topically. These papers all showed either negative or no consequences when rate of tissue regeneration was measured. This newest investigation shows, however, that SEG matrix sustains a steady release of oil, creating a completely different experimental condition than those conducted previously. The results obtained using SEG-FO as a wound dressing could prove to be tremendous in the field of tissue regeneration. Increased local angiogenesis due to up-regulation of vascular endothelial growth factor (VEGF) could be used therapeutically beyond just topical wound healing; in the future, SEG-mediated delivery has much clinical potential because of its stimulatory effects on angiogenesis and tissue repair while maintaining an efficient cost compared to alternatives such as gene therapy.
3 comments:
I understand that comparing the SEG-OO and SEG-FO results are probably the most interesting, but how did they compare to the controls? How much faster or better was the wound healing process with SEGs compared to dry guaze or the bioaqua thing?
This is a rather interesting article to read because of its research in something that can have direct clinical applications. To clarify if I understand correctly, the publication is talking about dispersion and delivery of polyunsaturated fatty acids (specifically n3-fatty acids) because of their up-regulation of lipid transport genes. In this case, I was wondering how many trials they ran and if they had any statistical variations resulting from the SEG-FO, or of they tried other types of oils such as flax (linseed), which often have greater concentrations of this type of fatty acid.
The researchers showed that the SEG-FO showed statistically significant closing first, which means it's the fastest. When comparing wound closure area, however, the comparisons between the SEG-FO and controls did not reach statistical significance although the SEG-FO did have the largest closure area.
Not sure I understand your question, Nikit, but they tested the the regulation of the genes using a microarray of selected sequences. I have heard of flax seeds and their omega-3 fatty acid content, but I'm not sure how they compare to fish oils. If they do have higher concentrations, it would be a good substitute for future tests.
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