Bioengineered chitosan/silk scaffold encapsulated with quercetin nanoparticles accelerates wound healing in a diabetic rat skin defect model

Abstract

Chronic wounds, particularly in diabetic patients, are characterized by prolonged inflammation, impaired angiogenesis, and delayed tissue regeneration. To address these challenges, the author developed a bioactive scaffold by incorporating quercetin nanoparticles (Qn) into a chitosan/silk fibroin (ChS) matrix, aiming to accelerate and enhance the wound healing process. Quercetin nanoparticles were synthesized via a solvent displacement method and incorporated into a ChS scaffold using a blending and freeze-drying technique. The physicochemical properties of the scaffold, including porosity, swelling ratio, degradation profile, biocompatibility, mechanical properties, and drug release kinetics, were characterized. Full-thickness excisional wounds (20 mm) were created on the dorsum of streptozotocin-induced diabetic Wistar rats, which were divided into three groups (n = 5): untreated control, ChS, and Qn-loaded ChS (QnChS). Wound closure was monitored on days 7 and 14. Histological evaluations (H&E and Masson's Trichrome) assessed tissue regeneration, vascularization, and collagen deposition. Cytokine levels (bFGF, VEGF, TNF-α, IL-1β) were quantified using ELISA. The QnChS scaffolds displayed a porous structure with sustained drug release over 14 days and enhanced biodegradability. In vivo, the QnChS group showed significantly accelerated wound contraction, increased dermal thickness and epidermal length, and higher collagen deposition compared to the other groups (p < 0.05). Angiogenesis was notably improved, evidenced by a higher number of blood vessels and elevated VEGF levels. Additionally, QnChS scaffolds markedly reduced TNF-α and IL-1β while increasing bFGF expression, indicating enhanced resolution of inflammation and promotion of tissue regeneration. The Qn-loaded ChS scaffold effectively modulates the inflammatory response, promotes angiogenesis, and enhances dermal regeneration in diabetic wounds. These findings suggest its potential as a multifunctional wound dressing for managing chronic wounds in diabetic patients.

Keywords: Chitosan; Diabetes; Nanoparticles; Quercetin; Rat skin; Scaffold; Silk; Wound healing.