Dual stimuli-responsive polyurethane-based hydrogels as smart drug delivery carriers for the advanced treatment of chronic skin wounds

The design of multi-stimuli-responsive vehicles for the controlled and localized release of drugs is a challenging issue increasingly catching the attention of many research groups working on the advanced treatment of hard-to-close wounds.In this work,a thermo-and pH-responsive hydrogel(P-CHP407)was prepared from an ad hoc synthesized amphiphilic poly(ether urethane)(CHP407)exposing a significant amount of-COOH groups(8.8±0.9 nmol/g_(polymer)).The exposure of acid moieties in P-CHP407 hydrogel led to slightly lower initial gelation temperature(12.1◦C vs.14.6◦C,respectively)and gelation rate than CHP407 hydrogel,as rheologically assessed.Nanoscale hydrogel characterization by Low Field NMR(LF-NMR)spectroscopy suggested that the presence of carboxylic groups in P-CHP407 caused the formation of bigger micelles with a thicker hydrated shell than CHP407 hydrogels,as further proved by Dynamic Light Scattering analyses.In addition,P-CHP407 hydrogel showed improved capability to change its internal pH compared to CHP407 one when incubated with an alkaline buffer(pH 8)(e.g.,pH_(change_5min)=3.76 and 1.32,respectively).Moreover,LF-NMR characterization suggested a stronger alkaline-pH-induced interaction of water molecules with micelles exposing-COOH groups.Lastly,the hydrogels were found biocompatible according to ISO 10993 and able to load and release Ibuprofen:delivery kinetics of Ibuprofen was enhanced by P-CHP407 hydrogels at alkaline pH,suggesting their potential use as smart delivery systems in the treatment of chronic infected wounds.

Strategies and challenges in the treatment of chronic venous leg ulcers

Evaluating patients with chronic venous leg ulcers(CVLUs)is essential to find the underlying etiology.The basic tenets in managing CVLUs are to remove the etiological causes,to address systemic and metabolic conditions,to examine the ulcers and artery pulses,and to control wound infection with debridement and eliminating excessive pressure on the wound.The first-line treatments of CVLUs remain wound care,debridement,bed rest with leg elevation,and compression.Evidence to support the efficacy of silver-based dressings in healing CVLUs is unavailable.Hydrogen peroxide is harmful to the growth of granulation tissue in the wound.Surgery options include a high ligation with or without stripping or ablation of the GSVs depending on venous reflux or insufficiency.Yet,not all CVLUs are candidates for surgical treatment because of comorbidities.When standard care of wound for 4 wk failed to heal CVLUs effectively,use of advanced wound care should be considered based on the available evidence.Negative pressure wound therapy facilitates granulation tissue development,thereby helping closure of CVLUs.Autologous split-thickness skin grafting is still the gold standard approach to close huge CVLUs.Hair punch graft appears to have a better result than traditional hairless punch graft for CVLUs.Application of adipose tissue or placenta-derived mesenchymal stem cells is a promising therapy for wound healing.Autologous platelet-rich plasma provides an alternative strategy for surgery for safe and natural healing of the ulcer.The confirmative efficacy of current advanced ulcer therapies needs more robust evidence.

Wound dressing products:A translational investigation from the bench to the market

Chronic skin wounds affect more than 40 million patients globally and represent a severe growing burden for the healthcare systems,with annual costs expected to exceed$15 billions by 2022.To satisfy the huge demand for effective wound care products,different types of wound dressings have been introduced on the market dur-ing the last decades.Based on“the moist wound healing theory”postulated by Prof Winter in 1962,bandages were initially designed to recreate the optimal wound environment to favor the healing process.Then,thanks to the advancements achieved in biomaterial design and processing,biotechnology,imaging and electronic fields,great effort has been devoted to the development of formulations able to actively participate to tissue healing.Indeed,both the literature and the market report the design of medicated wound dressings,i.e.,wound care products releasing anti-microbial agents,anti-inflammatory drugs,or bioactive molecules.In this scenario,this review aims at critically describing the currently available wound care products,highlighting their proved effec-tiveness in wound management.Moreover,an overview of the main strategies exploited to design personalized wound dressings has been reported.Lastly,concerns on regulatory affairs and practical issues limiting the clinical translation of advanced research platforms have also been discussed.