Multifunctional bioactive core-shell electrospun membrane capable to terminate inflammatory cycle and promote angiogenesis in diabetic wound

Abstract

Diabetic wound (DW) healing is a major clinical challenge due to multifactorial complications leading to prolonged inflammation. Electrospun nanofibrous (NF) membranes, due to special structural features, are promising biomaterials capable to promote DW healing through the delivery of active agents in a controlled manner. Herein, we report a multifunctional composite NF membrane loaded with ZnO nanoparticles (NP) and oregano essential oil (OEO), employing a new loading strategy, capable to sustainedly co-deliver bioactive agents. Physicochemical characterization revealed the successful fabrication of loaded nanofibers with strong in vitro anti-bacterial and anti-oxidant activities. Furthermore, in vivo wound healing confirmed the potential of bioactive NF membranes in epithelialization and granulation tissue formation. The angiogenesis was greatly prompted by the bioactive NF membranes through expression of vascular endothelial growth factor (VEGF). Moreover, the proposed NF membrane successfully terminated the inflammatory cycle by downregulating the pro-inflammatory cytokines interleukin −6 (IL-6) and matrix metalloproteinases-9 (MMP-9). In vitro and in vivo studies revealed the proposed NF membrane is a promising dressing material for the healing of DW.

Zinc Oxide Nanoparticles Exhibit Favorable Properties to Promote Tissue Integration of Biomaterials

“…We chose this setting to assess the sole effect of ZnO NPs in a wide concentration range from 1 µg/ml to 100 µg/mL independent of the transplant or implant material that is later chosen for the potential clinical application. ZnO NPs can be embedded in a variety of materials, among them gelatin [47], cellulose [22,61], alginate [20,[62][63][64], silica gels [65], chitosan [22,62,64,[66][67][68][69][70], different hydrogels [20][21][22]67,71,72], polycaprolactone [45,70,[73][74][75][76][77], polyvinyl alcohol [63,66], poly (vinlidene fluoride-trifluoroethylene) [45], polyurethane [62], calcium phosphate [78], polymethylmethacrylate [79], and polylactic acid [80], demonstrating the huge spectrum of biomaterials that can be modified using ZnO NPs. Since the CAM assay is an experiment that is not carried out with genetically identical organisms and during the highly dynamic embryonic development, it is a system that is subject to large interindividual variations.…”

Emerging Theranostic Nanomaterials in Diabetes and Its Complications

“…Incorporating antioxidant NPs into wound dressings may further improve performance by accelerating the wound healing process. [ 304 ] Augustine et al [ 305 ] prepared an electrospun poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV) membranes with antioxidant CeO 2 NPs (nCeO 2 ) for diabetic wound repair ( Figure 22 A ). As a result of the antioxidant and angiogenic activities of nCeO 2 NPs, the nCeO 2 ‐loaded electrospun membranes (PHBV/nCeO 2 ) exhibited excellent cytocompatibility for cell adhesion, cell proliferation, cell migration, and angiogenesis in vivo.…”

“…When used as a wound dressing in diabetic rats, the antioxidant membranes PHBV/nCeO 2 showed considerably enhanced diabetic wound healing properties compared to the nCeO 2 ‐free membrane (PHBV). In addition, Khan et al [ 304 ] developed a ZnO‐loaded core‐shell electrospun membrane for the treatment of diabetic wounds (Figure 22B ). To enhance efficiency, Atta et al employed oregano essential oil (OEO), an antioxidant and antibacterial natural plant extract.…”

Cyanobacteria-based self-oxygenated photodynamic therapy for anaerobic infection treatment and tissue repair

“…However, one-time medication is difficult to completely solve the infection problem especially for long-term chronic infections treatment. Long-term chronic inflammation is the physiological basis leading to immune system attack and wound non-healing [ 37 , 38 ]. It is well known that infection elimination, oxidative stress and inflammatory removal are indispensable requirements for tissue repair.…”