ECM Mimicking Biodegradable Nanofibrous Scaffold Enriched with Curcumin/ZnO to Accelerate Diabetic Wound Healing via Multifunctional Bioactivity

Abstract

Introduction Foot ulceration is one of the most severe and debilitating complications of diabetes, which leads to the cause of non-traumatic lower-extremity amputation in 15–24% of affected individuals. The healing of diabetic foot (DF) is a significant therapeutic problem due to complications from the multifactorial healing process. Electrospun nanofibrous scaffold loaded with various wound dressing materials has excellent wound healing properties due to its multifunctional action. Purpose This work aimed to develop and characterize chitosan (CS)-polyvinyl alcohol (PVA) blended electrospun multifunctional nanofiber loaded with curcumin (CUR) and zinc oxide (ZnO) to accelerate diabetic wound healing in STZ-induced diabetic rats. Results In-vitro characterization results revealed that nanofiber was fabricated successfully using the electrospinning technique. SEM results confirmed the smooth surface with web-like fiber nanostructure diameter ranging from 200 – 250 nm. An in-vitro release study confirmed the sustained release of CUR and ZnO for a prolonged time. In-vitro cell-line studies demonstrated significantly low cytotoxicity of nanofiber in HaCaT cells. Anti-bacterial studies demonstrated good anti-bacterial and anti-biofilm activities of nanofiber. In-vivo animal studies demonstrated an excellent wound-healing efficiency of the nanofibers in STZ–induced diabetic rats. Furthermore, the ELISA assay revealed that the optimized nanofiber membrane terminated the inflammatory phases successfully by downregulating the pro-inflammatory cytokines (TNF-α, MMP-2, and MMP-9) in wound healing. In-vitro and in-vivo studies conclude that the developed nanofiber loaded with bioactive material can promote diabetic wound healing efficiently via multifunction action such as the sustained release of bioactive molecules for a prolonged time of duration, proving anti-bacterial/anti-biofilm properties and acceleration of cell migration and proliferation process during the wound healing. Discussion CUR-ZnO electrospun nanofibers could be a promising drug delivery platform with the potential to be scaled up to treat diabetic foot ulcers effectively.

Approaches to Control and Monitor Protease Levels in Chronic Wounds

“…In addition to the above studies, a correlation between wound contraction and MMP-9, [108][109][110][111][112][113][114][115][116]56] and MMP-2 [113,117] levels was observed in other studies. This means wounds that healed or recovered more quickly had a lower extent of these proteases (or their genes or their activity) than wounds that healed to a lesser extent (of course, in many cases, normalized to the protein content).…”

“…prepared electrospun fibrous webs composed of polyvinyl alcohol (PVA) and chitosan containing curcumin and zinc oxide. [ 113 ] MMP‐2 and MMP‐9 in the wounds of the rats, that diabetic was induced in them through injection of Streptozotocin and treated with the developed material were lower than in controls. It is not clear how the control group was treated; it seems they were left untreated.…”

Biomimicking dual drug eluting twisted electrospun nanofiber yarns for post-operative wound healing

“…Both the formulated nanofiber yarns showed significant reduction in the IL-6 and TNF-α level throughout the study, providing strong support to our experimental report. Comparative wound healing potential of commercially available silk suture with VCN and FA load nanofiber yarns in rat skin wounds suggested insights on the benefits of advanced manufacturing techniques for nanofiber yarn synthesis intended for surgical suturing applications [52].…”

Electrospun Nanofiber Scaffold for Skin Tissue Engineering: A Review

“…66 Moreover, PVP and PVA have frequently been employed as central fibers within core−shell structures for drug slow-release systems. 67 3.3. Composites.…”