Honey loaded silk fibroin 3D porous scaffold facilitates homeostatic full-thickness wound healing

Abstract

Dermal reconstruction in acute and chronic wounds needs highly vascularized dermal tissue engineered skin substitutes which has the potentiality to provide physical cues as well as biological cues for scarless regenerative wound healing. Herein, we have investigated blends of silk fibroin and honey as a wound healing substrate that able to facilitate keratinocyte and fibroblast adhesion, migration and proliferation. Honey-silk fibroin (HSF) three dimensional (3D) scaffolds were fabricated by freeze drying and characterized in detailed for their physico-chemical, mechanical, swelling and degradable properties. Interestingly, in vitro studies showed better adhesion, proliferation and homogenous distribution of fibroblasts within blended scaffolds especially with 4% honey concentration (HSF4). Also, its structural composition with pores size ~ 139 µm and porosity 87% further confirms the superiority over the counterparts and other blended scaffolds. The in vitro cytotoxic studies illustrated the biocompatibility, proliferation and proper infiltration of primary fibroblasts within HSF4 scaffolds, validated by in vivo studies. Fascinatingly, in vivo cutaneous wound healing studies demonstrated the attainment of normal homeostasis with proper re-epithelialization, collagen matrix remodeling having high collagen I expression in respect to collagen III with minimal scar under HSF4 scaffold implantation. Taken together, this study suggests the potentiality of incorporation of honey component as a payload which not only augmented the scarless healing also modified the physical properties of scaffold in order to provide the suitable micro-ambience for healing and these material scaffold proved to be a potential dermal substitute for acute as well as chronic wounds. Statement of SignificanceThe 3D honey based porous scaffolds are increasingly getting attention in the field of biomedicine and wound healing due to their ability to mimic the architecture of native microenvironment and could provide the controlled release of honey at the affected area for fast regeneration. In this work we demonstrated that the addition of honey in SF scaffold not only enhanced the biological activity of scaffold also modulated the physico-chemical properties which ultimately helps in attaining fast homeostatic wound healing. The synergy of pore size, porosity and mechanical strength of scaffold having 4% honey concentration showed its potentiality in augmenting proper re-epithelialization, collagen matrix deposition and skin appendages formation which presents this scaffold as potential candidate in skin tissue engineering applications.