Anisotropic Biomimetic Silk Scaffolds for Improved Cell Migration and Healing of Skin Wounds

Abstract

Improved and more rapid healing of full-thickness skin wounds remains a major clinical need. Silk fibroin (SF) is a natural protein biomaterial that has been used in skin repair. However, there has been little effort aimed at improving skin healing through tuning the hierarchical microstructure of SF-based matrices and introducing multiple physical cues. Recently, enhanced vascularization was achieved with SF scaffolds with nanofibrous structures and tunable secondary conformation of the matrices. We hypothesized that anisotropic features in nanofibrous SF scaffolds would promote cell migration, neovascularization, and tissue regeneration in wounds. To address this hypothesis, SF nanofibers were aligned in an electric field to form anisotropic porous scaffolds after lyophilization. In vitro and in vivo studies indicated good cytocompatibility, and improved cell migration and vascularization than nanofibrous scaffolds without these anisotropic features. These improvements resulted in more rapid wound closure, tissue ingrowth, and the formation of new epidermis, as well as higher collagen deposition with a structure similar to the surrounding native tissue. The new epidermal layers and neovascularization were achieved by day 7, with wound healing complete by day 28. It was concluded that anisotropic SF scaffolds alone, without a need for growth factors and cells, promoted significant cell migration, vascularization, and skin regeneration and may have the potential to effectively treat dermal wounds.

Microskin‐Inspired Injectable MSC‐Laden Hydrogels for Scarless Wound Healing with Hair Follicles

“…The stability of the SFN and SFN‐P composite hydrogels was assessed by measuring the rheological behavior under constant frequency over the temperate range of 22–40 °C. [ 12,13,19 ]…”

“…Nine to ten week old Sparague‐Dawley (SD) adult male rats were used for the in vivo wound experiments. [ 12,13 ] All animal experiments were approved by the Animal Care and Experiment Committee of the Soochow university (approval number 201905A182, 201906A340, and 201907A108, Suzhou, China). Thirty SD rats were randomly distributed to six groups: blank, SFN, SFN‐LP hydrogels, BMSCs in medium, BMSCs blended with SFN hydrogels (SFN‐BMSCs hydrogels), and BMSC‐loaded on LP particles and then blended with SFN hydrogels (SFN‐LP‐BMSCs hydrogels).…”

“…Both SFN‐based scaffolds and hydrogels were fabricated to stimulate tissue ingrowth, resulting in better wound healing. [ 12,13 ] SFN hydrogels with aligned topography were then developed in our group to form better niches with multiple cues. [ 14 ] Unlike unaligned SFN hydrogels, the aligned SFN hydrogels could regulate the secretion of different cytokines and growth factors from SCs, achieving long‐term stemness of the SCs without exogeneous grow factors and fibroblasts (data not shown).…”

“…[ 15b ] Although the aligned hydrogels could be lyophilized to form anisotropic scaffolds to facilitate the ingrowth of blood vessel and granulation tissue during the wound healing process, the loss of hydrogel state weakened the niches with multiple cues, resulting in the wound healing without hair follicle regeneration. [ 13 ] Novel strategies are required to maintained the functions of multiple cues fully, optimzing the control of cell behaviors and skin regeneration. Here, aligned SFN hydrogels were modified to form microparticles without the destroy of aligned microstructures.…”

Structure and properties of PVA/silk fibroin hydrogels and their effects on growth behavior of various cell types

“…Therefore, the content of silk fibroin in PVA hydrogel may be one of the factors that affect cell morphology. Although silk fibroin hydrogels are beneficial for stem cell growth and differentiation [20,21], and silk fibroin composite scaffolds are also widely studied, such as silk fibroin/chitosan/graphene oxide scaffolds [22] and silk fibroin/chitosan/bioactive glass nanoparticle scaffolds [23]. These studies indicated that the composition and content of silk fibroin in composite scaffolds play an important role in cell morphology and behavior.…”