@misc{,
 copyright={Creative Commons Attribution BY 4.0 license},
 howpublished={online},
 school={Mossakowski Medical Research Center PAS},
 abstract={Improperly treated diabetes leads to ulcers, which in many cases end in the amputation of the limb. So far, no effective dressing has been found for difficult-to-heal wounds such asdiabetic foot ulcers.In the professional literature, among the compounds that can promote wound healing,opioids and substance P (SP) are mentioned. Therefore, in my doctoral dissertation, I decidedto investigate the effect of two hybrid compounds AWL3106 and biphalin, which are opioidand SP derivatives, in a difficult-to-heal wound model. The choice of these compounds isadditionally helpful in view of their analgesic activity.None of the animal models fully reflect human disease. The induction of diabetes in ratswith the use of a chemical agent – streptozotocin (STZ), does not lead to the formation ofspontaneous wounds, and the wound induced by skin excision in these animals does not fullyreflect the difficult-to-heal wound. Therefore, in my dissertation, the wound healing impairmentwas obtained by skin burn of a diabetic rat. Diabetes was induced with STZ, which destroys βcells responsible for insulin secretion. A burn wound was induced 10 weeks after STZadministration.Obtaining a difficult-to-heal wound allowed for proper research. The effect of thecompound AWL3106 and biphalin on selected parameters in the healing wound was assessed.The tested compounds were adsorbed on keratin preparations made of alpaca wool, whichserved as scaffolding. The tested neuropeptides and keratin preparations were synthesized /prepared according to the procedure developed by the late Professor Andrzej W. Lipkowski.Their action was compared to the negative and positive control, i.e., a difficult-to-heal woundnot treated with any compound and treated with a commercial ointment - iruxol®mono.The effectiveness of the tested compounds was assessed based on a scale speciallydeveloped for the purposes of my doctorate, which considered the influence of the compoundson wound contraction, the number of macrophages, fibroblasts, blood vessels, collagen contentand epidermis thickness.The results showed that the compound AWL3106: accelerated the process of woundcontraction, increased the number of macrophages and shortened the time for the infiltration ofthese cells in the wound, as well as increased the collagen content. Biphalin also had a positiveeffect on a difficult-to-heal wound: it accelerated the process of wound contraction, increasedthe number of macrophages and the thickness of the epidermis. The wounds healed better with 4both test compounds compared to iruxol®mono. Non-incrusted keratin preparations did notaffect the processes taking place in difficult-to-heal wounds.The obtained results allowed for the following conclusions: both tested compounds:AWL3106 and biphalin are good candidates for clinical trials on the process of diabetic woundhealing. Moreover, the developed model of a diabetic wound proved successful in assessing theinfluence of the studied neuropeptides, which may be used in the treatment of diabetic woundsin the future.},
 type={Text},
 URL={http://rcin.org.pl/Content/234925/PRACA%20DOKTORSKA%20-%20Adriana%20Muchowska%202021_l.pdf},
}