RESUMEN
The proficient handling of diabetic wounds, a rising issue coinciding with the global escalation of diabetes cases, poses significant clinical difficulties. A range of biofunctional dressings have been engineered and produced to expedite the healing process of diabetic wounds. This study proposes a multifunctional hydrogel dressing for diabetic wound healing, which is composed of Polyvinyl Alcohol (PVA) and N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1, N1, N3, N3-teramethylpropane-1, 3-diaminium (TSPBA), and a dual-drug loaded Gelatin methacryloyl (GM) microgel. The GM microgel is loaded with sodium fusidate (SF) and nanoliposomes (LP) that contain metformin hydrochloride (MH). Notably, adhesive and self-healing properties the hydrogel enhance their therapeutic potential and ease of application. In vitro assessments indicate that SF-infused hydrogel can eliminate more than 98% of bacteria within 24 h and maintain a sustained release over 15 days. Additionally, MH incorporated within the hydrogel has demonstrated effective glucose level regulation for a duration exceeding 15 days. The hydrogel demonstrates a sustained ability to neutralize ROS throughout the entire healing process, predominantly by electron donation and sequestration. This multifunctional hydrogel dressing, which integrated biological functions of efficient bactericidal activity against both MSSA and MRSA strains, blood glucose modulation, and control of active oxygen levels, has successfully promoted the healing of diabetic wounds in rats in 14 days. The hydrogel dressing exhibited significant effectiveness in facilitating the healing process of diabetic wounds, highlighting its considerable promise for clinical translation.
Asunto(s)
Antibacterianos , Vendajes , Hidrogeles , Alcohol Polivinílico , Especies Reactivas de Oxígeno , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Especies Reactivas de Oxígeno/metabolismo , Ratas , Antibacterianos/farmacología , Antibacterianos/química , Alcohol Polivinílico/química , Masculino , Hiperglucemia/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Ratas Sprague-Dawley , Gelatina/química , Metformina/farmacología , Metformina/química , Liposomas/química , Staphylococcus aureus/efectos de los fármacos , Metacrilatos/química , Metacrilatos/farmacología , Adhesivos/química , Adhesivos/farmacología , InyeccionesRESUMEN
Diabetic wounds pose a challenge to healing due to increased bacterial susceptibility and poor vascularization. Effective healing requires simultaneous bacterial and biofilm elimination and angiogenesis stimulation. In this study, we incorporated polyaniline (PANI) and S-Nitrosoglutathione (GSNO) into a polyvinyl alcohol, chitosan, and hydroxypropyltrimethyl ammonium chloride chitosan (PVA/CS/HTCC) matrix, creating a versatile wound dressing membrane through electrospinning. The dressing combines the advantages of photothermal antibacterial therapy and nitric oxide gas therapy, exhibiting enduring and effective bactericidal activity and biofilm disruption against methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Escherichia coli. Furthermore, the membrane's PTT effect and NO release exhibit significant synergistic activation, enabling a nanodetonator-like burst release of NO through NIR irradiation to disintegrate biofilms. Importantly, the nanofiber sustained a uniform release of nitric oxide, thereby catalyzing angiogenesis and advancing cellular migration. Ultimately, the employment of this membrane dressing culminated in the efficacious amelioration of diabetic-infected wounds in Sprague-Dawley rats, achieving wound closure within a concise duration of 14 days. Upon applying NIR irradiation to the PVA-CS-HTCC-PANI-GSNO nanofiber membrane, it swiftly eradicates bacteria and biofilm within 5 min, enhancing its inherent antibacterial and anti-biofilm properties through the powerful synergistic action of PTT and NO therapy. It also promotes angiogenesis, exhibits excellent biocompatibility, and is easy to use, highlighting its potential in treating diabetic wounds.
Asunto(s)
Antibacterianos , Vendajes , Biopelículas , Óxido Nítrico , Terapia Fototérmica , Ratas Sprague-Dawley , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Óxido Nítrico/farmacología , Óxido Nítrico/metabolismo , Ratas , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/uso terapéutico , Biopelículas/efectos de los fármacos , Terapia Fototérmica/métodos , Masculino , Quitosano/química , Quitosano/farmacología , Nanofibras/química , Escherichia coli/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Diabetes Mellitus Experimental/complicaciones , Staphylococcus aureus/efectos de los fármacos , Alcohol Polivinílico/química , Alcohol Polivinílico/farmacología , S-Nitrosoglutatión/farmacología , S-Nitrosoglutatión/químicaRESUMEN
Diabetic wounds (DW) are constantly challenged by excessive reactive oxygen species (ROS) accumulation and susceptibility to bacterial contamination. Therefore, the elimination of ROS in the immediate vicinity and the eradication of local bacteria are critical to stimulating the efficient healing of diabetic wounds. In the current study, we encapsulated mupirocin (MP) and cerium oxide nanoparticles (CeNPs) into a polyvinyl alcohol/chitosan (PVA/CS) polymer, and then a PVA/chitosan nanofiber membrane wound dressing was fabricated using electrostatic spinning, which is a simple and efficient method for fabricating membrane materials. The PVA/chitosan nanofiber dressing provided a controlled release of MP, which produced rapid and long-lasting bactericidal activity against both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains. Simultaneously, the CeNPs embedded in the membrane exhibited the desired ROS scavenging capacity to maintain the local ROS at a normal physiological level. Moreover, the biocompatibility of the multifunctional dressing was evaluated both in vitro and in vivo. Taken together, PVA-CS-CeNPs-MP integrated the desirable features of a wound dressing, including rapid and broad-spectrum antimicrobial and ROS scavenging activities, easy application, and good biocompatibility. The results validated the effectiveness of our PVA/chitosan nanofiber dressing, highlighting its promising translational potential in the treatment of diabetic wounds.