Elucidating the role of silicone in the treatment of burn scars : an essential step in the development of improved treatment products

摘要

Hypertrophic scarring is a common occurrence for severe burn victims leading to major functional, physiological, and aesthetic effects to the patients. Limiting the hypertrophic scarring of the patients alleviates the functional, physiological, and aesthetic effects. ududSilicone gels, over the past decade, have been widely used to remediate and limit hypertrophic scarring but the mechanism of action is yet to be determined. One explanation has been that hydration of the outermost area of the burn is induced by the silicone gel . However, non-silicone polymers which increase hydration could not mimic the effect. An alternative interpretation is that there may be silicone species that migrate from the silicone gel into the viable tissue to mediate reactions in the extra-cellular matrix that result in a decreased deposition of excessive amounts of collagen - a central feature of the hypertrophic scar.ududA novel and informative technique to study these species is MALDI-TOF/MS (Matrix Assisted Laser Desorption Ionisation-Time of Flight Mass Spectrometry) in conjunction with gel permeation chromatography. MALDI-TOF/MS, which has allowed the detection of intact molecular species that were not possible with more established mass spectrometric techniques.ududThe mobile species that may migrate from polydimethylsiloxane medical gel sheeting into skin have been identified by MALDI-MS. The bulk gel contains predominantly cyclic oligomers with a mass distribution peaking at n = 19 (number of repeating siloxane units), but in an aqueous environment the species at the surface of the silicone medical gel are predominantly methyl/methylol-terminated linear siloxanes. By using a gelatine matrix as a model substrate, the distribution of silicon after application of the silicone gel for 16 weeks was determined by Energy-dispersive X-Ray mapping of the sectioned gelatine. The association of the linear and cyclic oligomers with proteins relevant in hypertrophic scarring are considered.ududThe mobility of silicone species across stratum corneum was confirmed by Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FT/IR). This method confirms our hypothesis that not only are the low molecular weight silicone species mobile, but also that they do traverse the natural barrier, the stratum corneum, to levels that are detectable by ATR after a continuous application over approximately 11 days.ududInvitro studies of the effects of LMWS on primary line fibroblast cells indicate a response that down regulates the proliferation of fibroblast cells and protein production. Preliminary results indicate that a family of pendant functional LMWS are effective in down regulating hypertrophic-derived fibroblast primary cells.ududStudies on hypertrophic scar tissue treated with silicone medical gel indicate that LMWS permeate across the stratum corneum into viable scar tissue. In some areas, the LMWS tend to pool as detected by SEM/EDX elemental silicon analysis. These areas of LMWS pooling tend to be composed of highly disorganised collagen nodules.