Multifunctional Medical Dressings For The Treatment Of Diabetic Chronic Wounds

As the number of diabetics worldwide increases,so does the need for care and treatment of chronic ulcer wounds,which are closely related to diabetes.There are a lot of studies on wound dressings,but there are very few dressings for diabetic chronic wounds.Due to the damage of immune function and blood vessel,diabetic's wound is easy to form chronic inflammation,involving excessive contents of inflammatory cells and inflammatory cytokines,reactive oxygen species(ROS)and proteases,and repeated bacterial infections,and do not heal for a long time.At present,the addition of antibiotics,anti-inflammatory drugs,and growth factors into the dressings is the main approach to eliminate chronic inflammation and promote proliferation.However,drug resistance,easy inactivation,and side effects of these bioactive agents cannot be ignored.A few studies have reported that the wound inflammation microenvironment can be regulated by dressing material itself.However,these materials only focus on individual causes of chronic inflammation,and the ensemble healing effect is often unsatisfactory.Electrospun fibers and hydrogels have attracted extensive attention in the field of medical dressings due to their unique advantages.Based on the cellular and molecular mechanism of chronic wounds,this paper designed a medical dressing for diabetic chronic wounds,which can be used to safely and cooperatively regulate the inflammatory microenvironment,promote proliferation,and speed up wound healing,mainly including the following three aspects:Firstly,thioether grafted high molecular weight hyaluronic acid(HHA)was electrospun and cross-linked by Fe3+ to construct crosslinked nanofibers(FHHA-S/Fe).After being applied on the chronic diabetic wound bed,FHHA-S/Fe would form a nanofibrous hydrogel after absorbing wound exudate,which would be completely absorbed in a time frame(within 3 days)matching typical dressing changes.The grafted thioethers on HHA can scavenge the ROS quickly in the early inflammation phase to relieve the inflammation reactions.Additionally,the HHA itself is able to promote the transformation of the gathered M1 macrophages to the M2 phenotype to improve the function of immune cells.On the chronic diabetic wound model,the average remaining wound area after FHHA-S/Fe treatment is much smaller than that of other groups,especially in the early stage of wound healing,showing the excellent anti-inflammatory and pro-healing properties.Additionly,HHA/poly(vinyl alcohol)(PVA)mixture was treated with Cu2+cross-linking of low degree and physical cross-linking(one freeze-thaw cycle and unique lyophilization)to construct Cu-HHA/PVA hydrogels.M?2 were then seeded on the Cu-HHA/PVA hydrogels to form Cu-HHA/PVA@M?2 hydrogels.Cu-HHA/PVA@M?2 hydrogel can directly supply the M?2 in the wound site to relieve the immune cell dysfunction of diabetic wounds.Because of HHA,Cu-HHA/PVA@M?2 hydrogel can not only maintain the consistent phenotype of loaded M?2,but also transform the M1 phenotype macrophages(M?1)in the wound bed to M?2.Furthermore,Cu2+ could be released from the hydrogels to further stimulate angiogenesis.The average wound area after the 0.5Cu-HHA/PVA@M?2(ionic cross-linking degree 0.5%)treatment was much smaller than that of other diabetic groups at day 12 and close to that of the wild nondiabetic control group,showing the excellent promote healing effect.Finally,polylactic acid(PLA)nanofibers loaded with copper chelating curcumin(Cr-Cu)were prepared by electrospinning.The fibers were homogenized into short fibers,and then coated with polydopamine(PDA)on the surface.The short fibers were dispersed in the HHA/PVA mixture and form hydrogel((PLA/Cr-Cu)@PDA/HP)after six freeze-thawing cycles.Because of PDA,hydrogels have excellent photothermal effect.Meanwhile,the temperature rise increases the release of Cr-Cu,thus achieving excellent antibacterial effect at low temperature and low drug concentration.Additionally,Cr-Cu is also expected to play an antioxidant role and reduce protease levels.Meanwhile,HHA,the main material of hydrogel,is also expected to transform the M?1 in the wound bed to M?2 and play an anti-inflammatory role.