Mechanic-Driven Biodegradable Polyglycolic Acid/Silk Fibroin Nanofibrous Scaffolds Containing Deferoxamine Accelerate Diabetic Wound Healing

Abstract

The extracellular matrix (ECM), comprising of hundreds of proteins, mainly collagen, provides physical, mechanical support for various cells and guides cell behavior as an interactive scaffold. However, deposition of ECM, especially collagen content, is seriously impaired in diabetic wounds, which cause inferior mechanical properties of the wound and further delay chronic wound healing. Thus, it is critical to develop ECM/collagen alternatives to remodel the mechanical properties of diabetic wounds and thus accelerate diabetic wound healing. Here, we firstly prepared mechanic-driven biodegradable PGA/SF nanofibrous scaffolds containing DFO for diabetic wound healing. In our study, the results in vitro showed that the PGA/SF-DFO scaffolds had porous three-dimensional nanofibrous structures, excellent mechanical properties, biodegradability, and biocompatibility, which would provide beneficial microenvironments for cell adhesion, growth, and migration as an ECM/collagen alternative. Furthermore, the data in vivo showed PGA/SF-DFO scaffolds can adhere well to the wound and have excellent biodegradability, which is helpful to avoid secondary damage by omitting the removal process of scaffolds. The finite element analysis results showed that the application of silk fibroin-based scaffolds could significantly reduce the maximum stress around the wound. Besides, PGA/SF-DFO scaffolds induced collagen deposition, re-vascularization, recovered impaired mechanical properties up to about 70%, and ultimately accelerated diabetic wound healing within 14 days. Thus, our work provides a promising therapeutic strategy for clinically chronic wound healing.

Qualitative study on diabetic cutaneous wound healing with radiation crosslinked bilayer collagen scaffold in rat model

“…CD31 expression levels increased on day 21. The encouraging findings were consistent with other studies 1 , 3 , 6 .

Figure 6 Representative immunohistochemical staining images of CD31 on ( A ) dermis and ( B ) epidermal layer on days 7, 14 and 21 in rcBCS group.

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“…CD31 expression levels increased on day 21. The encouraging findings were consistent with other studies 1,3,6 .…”

“…Masson's trichrome stain indicated collagen deposition at the wound sites. Collagen deposition was thought to be an intuitive assessment indicator of wound modeling 6 . Images of Masson's trichrome staining showed that collagen deposition was accelerated by rcBCS compared to sham operation group (Fig.…”

“…However, the ECM, as cell interactive scaffold, provides mechanical support for adhesion, proliferation, and migration of various cells. Therefore, it is vital to develop ECM-like/collagen substitute to remodel the mechanical properties of the wound and thus accelerate diabetic wound healing 6 .…”

New insights into balancing wound healing and scarless skin repair

“…Bastidas et al 174 Fibronectin It plays a significant role in cell migration, adhesion, proliferation, hemostasis, and tissue repair. Fibronectin based wound dressings can promote epithelialization and reduce scar formation Mogoşanu and Grumezescu 165 Silk fibroin It stimulates stem cell adhesion, proliferation and migration, enhances tissue healing ability and inhibits pathological adhesion Zha et al 175 Sericin It enhances cell adhesion, promotes cell proliferation, and inhibits inflammatory response and pit oxidation activity El-Samad et al 176 Chitosan Macromolecular material with biocompatibility, biodegradation, antibacterial, implantable and biological activity. It is considered to be a very ideal wound dressing.…”