RESUMO
Diabetic skin wound healing is compromised by bacterial infections, oxidative stress, and vascular disruption, leading to delayed recovery and potential complications. This study developed an antibacterial, antioxidant, and adhesive hydrogel dressing that promotes rapid bacterial-infected diabetic wound healing using the biological macromolecule of polydopamine (PDA). This hydrogel comprised PDA-armored zeolitic imidazolate framework-8 nanoparticles (PDA@ZIF-8 NPs) combined with a second armor of zwitterionic polymer network (poly(acrylamide-co-sulfobetaine methacrylate); PAS), realizing low concentration Zn2+ release, good adhesion (14.7 kPa for porcine skin), and improved tensile strength (83.2 kPa). The hydrogel exhibited good antibacterial efficacy against both Staphylococcus aureus (S. aureus, 92.8 %), Escherichia coli (E. coli, 99.6 %) and methicillin-resistant S. aureus (MRSA, 99.2 %), which was attributed to the properties of the incorporated PDA@ZIF-8 NPs. Notably, in vitro, the PDA@ZIF-8 PAS hydrogel not only promoted fibroblast proliferation and migration but also facilitated endothelial cell angiogenesis. In vivo, the PDA@ZIF-8 PAS hydrogel retained its Zn2+-releasing function and effectively suppressed bacterial growth in infected wounds, thereby accelerating the regeneration of both normal and diabetic wounds. This multiarmored hydrogel is a promising sustained-release carrier for functional metal ions and drugs, making it applicable for not only skin healing, but potentially the regeneration of other complex tissues.
Assuntos
Antibacterianos , Hidrogéis , Indóis , Estruturas Metalorgânicas , Polímeros , Cicatrização , Indóis/química , Indóis/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Polímeros/química , Polímeros/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Camundongos , Zeolitas/química , Zeolitas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Zinco/química , Zinco/farmacologia , Humanos , Suínos , Nanopartículas/química , Fibroblastos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacosRESUMO
Most of the current bioadhesives cannot perform well on bleeding tissues while postoperative adhesion is a general but serious clinical issue. Here, a three-layer biodegradable Janus tissue patch (J-TP) that is able to simultaneously enable efficient closure of bleeding wounds with significantly promoted clotting ability and suppressed postoperative adhesion of tissues is reported. A dry adhesive hydrogel bottom layer of the J-TP can form rapid (within 15 s) and strong (tensile strength up to 98 kPa) adhesion to bleeding/wet tissues with high bursting pressure (about 312.5 mmHg on a sealed porcine skin) through hydrogen binding and covalent conjugation between the carboxyl & N-hydroxy succinimide (NHS) groups of hydrogel and the primary amine groups of tissues, while the phosphonic motifs can significantly reduce blood loss (by 81% on a rat bleeding liver model) of bleeding wounds. A thin polylactic acid (PLA) middle layer can improve the tensile strength (by 132%) of the J-TP in wet conditions while the grafted zwitterionic polymers can effectively prevent postoperative tissue adhesion and inflammatory reaction. This J-TP may be a promising tissue patch to assist the clinical treatment of injured bleeding tissues with inhibited postoperative adhesion.