RESUMEN
Impaired wound healing is a significant complication of diabetes. Platelet-derived extracellular vesicles (pEVs), rich in growth factors and cytokines, show promise as a powerful biotherapy to modulate cellular proliferation, angiogenesis, immunomodulation, and inflammation. For practical home-based wound therapy, however, pEVs should be incorporated into wound bandages with careful attention to delivery strategies. In this work, a gelatin-alginate hydrogel (GelAlg) loaded with reduced graphene oxide (rGO) was fabricated, and its potential as a diabetic wound dressing was investigated. The GelAlg@rGO-pEV gel exhibited excellent mechanical stability and biocompatibility in vitro, with promising macrophage polarization and reactive oxygen species (ROS)-scavenging capability. In vitro cell migration experiments were complemented by in vivo investigations using a streptozotocin-induced diabetic rat wound model. When exposed to near-infrared light at 2 W cm- 2, the GelAlg@rGO-pEV hydrogel effectively decreased the expression of inflammatory biomarkers, regulated immune response, promoted angiogenesis, and enhanced diabetic wound healing. Interestingly, the GelAlg@rGO-pEV hydrogel also increased the expression of heat shock proteins involved in cellular protective pathways. These findings suggest that the engineered GelAlg@rGO-pEV hydrogel has the potential to serve as a wound dressing that can modulate immune responses, inflammation, angiogenesis, and follicle regeneration in diabetic wounds, potentially leading to accelerated healing of chronic wounds.
Asunto(s)
Plaquetas , Complicaciones de la Diabetes , Vesículas Extracelulares , Cicatrización de Heridas , Plaquetas/química , Vesículas Extracelulares/química , Oxidación-Reducción , Complicaciones de la Diabetes/tratamiento farmacológico , Humanos , Animales , Ratones , Ratas , Línea Celular , Ratas Wistar , Supervivencia Celular , Especies Reactivas de Oxígeno/metabolismo , Hidrogeles/químicaRESUMEN
Long-standing administration of disease-modifying antirheumatic drugs confirms their clinical value for managing rheumatoid arthritis (RA). Nevertheless, there are emergent worries over unwanted adverse risks of systemic drug administration. Hence, a novel strategy that can be used in a drug-free manner while diminishing side effects is immediately needed, but challenges persist in the therapy for RA. To this end, herein we conjugated tyramine (TYR) with alginate (ALG) to form ALG-TYR and then treated it for 5 min with oxygen plasma (ALG-TYR + P/5 min). It was shown that the ALG-TYR + P/5 min hydrogel exhibited favorable viscoelastic, morphological, mechanical, biocompatible, and cellular heat-shock protein amplification behaviors. A thorough physical and structural analysis was conducted on the ALG-TYR + P/5 min hydrogel, revealing favorable physical characteristics and uniform porous structural features within the hydrogel. Moreover, ALG-TYR + P/5 min not only effectively inhibited inflammation of RA but also potentially regulated lesion immunity. Once ALG-TYR + P/5 min was intra-articularly administered to joints of rats with zymosan-induced arthritis, we observed that ALG-TYR + P/5 min could ameliorate syndromes of RA joint. This bioinspired and self-restorable ALG-TYR + P/5 min hydrogel can thus serve as a promising system to provide prospective outcomes to potentiate RA therapy.
RESUMEN
The skin possesses an epithelial barrier. Delivering growth factors to deeper wounds is usually rather challenging, and these typically restrict the therapeutic efficacy for chronic wound healing. Efficient healing of chronic wounds also requires abundant blood flow. Therefore, addressing these concerns is crucial. Among presently accessible biomedical materials, tailored hydrogels are favorable for translational medicine. However, these hydrogels display insufficient mechanical properties, hampering their biomedical uses. Cold-atmospheric plasma (CAP) has potent cross-linking/polymerizing abilities. The CAP was characterized spectroscopically to identify excited radiation and species (hydroxyl and UV). CAP was used to polymerize pyrrole (creating Ppy) and crosslink hybrid polymers (Ppy, hyaluronic acid (HA), and gelatin (GEL)) as a multimodal dressing for chronic wounds (CAP-Ppy/GEL/HA), which were used to incorporate therapeutic platelet proteins (PPs). Herein, the physicochemical and biological features of the developed CAP-Ppy/GEL/HA/PP complex were assessed. CAP-Ppy/GEL/HA/PPs had positive impacts on wound healing in vitro. In addition, the CAP-Ppy/GEL/HA complex has improved mechanical aspects, therapeutics sustained-release/retention effect, and near-infrared (NIR)-driven photothermal-hyperthermic effects on lesions that drive the expression of heat-shock protein (HSP) with anti-inflammatory properties for boosted restoration of diabetic wounds in vivo. These in vitro and in vivo outcomes support the use of CAP-Ppy/GEL/HA/PPs for diabetic wound regeneration.