RESUMO
The intricate microenvironment of diabetic wounds characterized by hyperglycemia, intense oxidative stress, persistent bacterial infection and complex pH fluctuations hinders the healing process. Herein, an injectable multifunctional hydrogel (QPTx) was developed, which exhibited excellent mechanical performance and triple responsiveness to pH, temperature, and glucose due to dynamic covalent cross-linking involving dynamic Schiff base bonds and phenylboronate esters with phenylboronic-modified quaternized chitosan (QCS-PBA), polydopamine coated tunicate cellulose crystals (PDAn@TCNCs) and polyvinyl alcohol (PVA). Furthermore, the hydrogels can incorporate insulin (INS) drugs to adapt to the complex and variable wound environment in diabetic patients for on-demand drug release that promote diabetic wound healing. Based on various excellent properties of the colloidal materials, the hydrogels were evaluated for self-healing, rheological and mechanical properties, in vitro insulin response to pH/temperature/glucose release, antibacterial, antioxidant, tissue adhesion, coagulation, hemostasis in vivo and in vitro, and biocompatibility and biodegradability. By introducing PDAn@TCNCs particles, the hydrogel has photothermal antibacterial activity, enhanced adhesion and oxidation resistance. We further demonstrated that these hydrogel dressings significantly improved the healing process compared to commercial dressings (Tegaderm™) in full-layer skin defect models. All indicated that the glucose-responsive QPTx hydrogel platform has great potential for treating diabetic wounds.
Assuntos
Antibacterianos , Bandagens , Celulose , Hidrogéis , Nanopartículas , Cicatrização , Cicatrização/efeitos dos fármacos , Celulose/química , Celulose/farmacologia , Celulose/análogos & derivados , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas/química , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Insulina/administração & dosagem , Urocordados/química , Quitosana/química , Polímeros/química , Polímeros/farmacologia , Masculino , Indóis/química , Indóis/farmacologia , Álcool de Polivinil/química , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Diabetes Mellitus Experimental/tratamento farmacológico , Camundongos , Ratos , Ratos Sprague-DawleyRESUMO
Wound dressing with an improved structural and functional recapitulation of damaged organs, efficient self-healing and antibacterial properties that can well integrate with tissue are urgently needed in wound management. Supramolecular hydrogels confer control over structural properties in a reversible, dynamic and biomimetic fashion. Herein, a kind of injectable, self-healing and antibacterial supramolecular hydrogel with multi-responses were fabricated by mixing phenylazo-terminated Pluronic F127, quaternized chitosan-graft-cyclodextrin and polydopamine coated tunicate cellulose nanocrystals under physiological conditions. By exploiting the photoisomerization of azobenzene under different wavelengths, a supramolecular hydrogel featuring a changing crosslink density of network was obtained. The corporation of polydopamine coated tunicate cellulose nanocrystals strengthens the hydrogel network with Schiff base bonds and hydrogen bonds, which avoids complete gel-sol transition. The inherent antibacterial property, drug release behavior, self-healing ability, hemostatic performance and biocompatibility were investigated to confirm superiority in wound healing. Moreover, the curcumin loaded hydrogel (Cur-hydrogel) showed multi-responsive release profiles (light, pH, and temperature). A full-thickness skin defect model was built to confirm that Cur-hydrogels significantly accelerated wound healing rate with better granulation tissue thickness and collagen disposition. Overall, the novel photo-responsive hydrogel with coherent antibacterial property has great potential in the healthcare of wound healing.
Assuntos
Quitosana , Nanopartículas , Hidrogéis/farmacologia , Hidrogéis/química , Celulose , Bandagens , Quitosana/química , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
Building stimulus-responsive units in the hydrogel coatings remains challenging for film sensors consisting of alternated layers of inert substrates and hydrogel coatings. An interesting film sensor with a carboxymethyl starch-based hydrogel coating was developed here. The cross-linking networks of carboxymethyl starch play the roles of structure-constructing units and stimulus-controlling units simultaneously, endowing the coatings with thermal sensing and strain sensing capabilities. The dynamic cross-links formed via the boronic ester bonds are temperature-sensitive, releasing or consuming additional acid ions with temperature alteration, and also as primary networks give the hydrogel strength and stretchability with the assistance of semi-penetrated polyacrylamide chains. Therefore, as-prepared flexible film sensors can be used to detect the periodic changes of human temperature and small-scale motion with multiple working modes, discriminating the physical states related to human health. Moreover, this kind of starch-based coating is degradable in a strongly alkaline solution and the inert substrate layer can protect the skin from erosion caused by direct hydrogel-skin contact, and thereby the film sensor is human- and environmentally friendly. This work also proposes a strategy of building temperature-sensitive units in the film sensor via regulating the chemical networks, instead of tuning physical structures.