Microporous Dermal-Mimetic Electrospun Scaffolds Pre-Seeded with Fibroblasts Promote Tissue Regeneration in Full-Thickness Skin Wounds

Abstract

Electrospun scaffolds serve as promising substrates for tissue repair due to their nanofibrous architecture and amenability to tailoring of chemical composition. In this study, the regenerative potential of a microporous electrospun scaffold pre-seeded with dermal fibroblasts was evaluated. Previously we reported that a 70% collagen I and 30% poly(Ɛ-caprolactone) electrospun scaffold (70:30 col/PCL) containing 160 μm diameter pores had favorable mechanical properties, supported fibroblast infiltration and subsequent cell-mediated deposition of extracellular matrix (ECM), and promoted more rapid and effective in vivo skin regeneration when compared to scaffolds lacking micropores. In the current study we tested the hypothesis that the efficacy of the 70:30 col/PCL microporous scaffolds could be further enhanced by seeding scaffolds with dermal fibroblasts prior to implantation into skin wounds. To address this hypothesis, a Fischer 344 (F344) rat syngeneic model was employed. In vitro studies showed that dermal fibroblasts isolated from F344 rat skin were able to adhere and proliferate on 70:30 col/PCL microporous scaffolds, and the cells also filled the 160 μm pores with native ECM proteins such as collagen I and fibronectin. Additionally, scaffolds seeded with F344 fibroblasts exhibited a low rate of contraction (~14%) over a 21 day time frame. To assess regenerative potential, scaffolds with or without seeded F344 dermal fibroblasts were implanted into full thickness, critical size defects created in F344 hosts. Specifically, we compared: microporous scaffolds containing fibroblasts seeded for 4 days; scaffolds containing fibroblasts seeded for only 1 day; acellular microporous scaffolds; and a sham wound (no scaffold). Scaffolds containing fibroblasts seeded for 4 days had the best response of all treatment groups with respect to accelerated wound healing, a more normal-appearing dermal matrix structure, and hair follicle regeneration. Collectively these results suggest that microporous electrospun scaffolds pre-seeded with fibroblasts promote greater wound-healing than acellular scaffolds.

Emerging Roles of Electrospun Nanofibers in Cancer Research

“…[107] Hence, many attempts have been made to develop 3D scaffolds with high porosity. [107–108] Towards this end, various approaches are being developed. For instance, electrospun fibers can be assembled into 3D scaffolds with cellular architecture through freeze-drying of solutions containing short electrospun nanofibers (Figure 3A).…”

Self Organized Skin Equivalent by Epithelial and Fibroblast Cells on Polycaprolactone Electrospun Mat with Porous Fibers

“…Adjusting the inter-fiber distance or introduction of micropores into the electrospun mat are examples of improving cell infiltration. 26 The inter fiber pore size and the distribution of the pores can be easily achieved by sacrificial components or adjusting the electrospinning conditions. 27 The HFDF cells seeded on the PPCL mat also showed similar infiltration into the inter fiber space with even distribution of cells.…”

Microbial Interactions with Nanostructures and their Importance for the Development of Electrospun Nanofibrous Materials used in Regenerative Medicine and Filtration

“…In another aspect of regenerative medicine, wound healing, electrospinning is now an established technique for the production of wound dressings for the treatment of chronic wounds [6,[29][30][31][32][33][34][35]. Many modern wound dressings are no longer only a barrier to protect a wound from infection but they are also expected to enhance the healing of the wound [36].…”