Silk Sponges Ornamented with a Placenta-Derived Extracellular Matrix Augment Full-Thickness Cutaneous Wound Healing by Stimulating Neovascularization and Cellular Migration

Abstract

Regeneration of full-thickness wounds without scar formation is a multifaceted process, which depends on in situ dynamic interactions between the tissue-engineered skin substitutes and a newly formed reparative tissue. However, the majority of the tissue-engineered skin substitutes used so far in full-thickness wound healing cannot mimic the natural extracellular matrix (ECM) complexity and thus are incapable of providing a suitable niche for endogenous tissue repair. Herein, we demonstrated a simple approach to fabricate porous hybrid ECM sponges (HEMS) using a placental ECM and silk fibroin for full-thickness wound healing. HEMS with retained cytokines/growth factors provided a noncytotoxic environment in vitro for human foreskin fibroblasts (HFFs), human epidermal keratinocytes (HEKs), and human amniotic membrane-derived stem cells to adhere, infiltrate, and proliferate. Interestingly, HEMS-conditioned media accelerated the migration of HFFs and HEKs owing to the presence of cytokines/growth factors. Also, the ex vivo chick chorioallantoic membrane assay of HEMS demonstrated its excellent vascularization potential by inducing and supporting blood vessels. Additionally, HEMS when subcutaneously implanted demonstrated no severe immune response to the host. Furthermore, HEMS implanted in full-thickness wounds in a rat model showed augmented healing progression with well-organized epidermal-dermal junctions via pronounced angiogenesis, accelerated migration of HFFs/HEKs, enhanced granulation tissue formation, and early re-epithelialization. Taken together, these findings show that porous HEMS ornamented with cytokines/growth factors having superior physicomechanical properties may be an appropriate skin substitute for full-thickness cutaneous wounds.

Core-Shell Nanofibrous Scaffold Based on Polycaprolactone-Silk Fibroin Emulsion Electrospinning for Tissue Engineering Applications

“…Together with its exceptional elasticity and minimal immunogenic response [ 24 ], silk fibroin (SF) has been universally accepted biopolymer in tissue engineering domain [ 25 , 26 ]. These very intrinsic disparities of both PCL and silk fibroin have been utilized in numerous research field of bone [ 27 , 28 , 29 ], skin, wound healing [ 30 , 31 , 32 ], tendon tissue engineering [ 33 ], vascular [ 34 , 35 , 36 ], and a myriad of other tissue engineering applications [ 37 , 38 , 39 ].…”

Therapeutic strategies for skin regeneration based on biomedical substitutes

“…Lately, many products have been developed and applied for therapeutic applications to mimic the native skin architecture and its microenvironment properties …”

“…[46][47][48] Therapeutic strategies for skin regeneration Lately, many products have been developed and applied for therapeutic applications to mimic the native skin architecture and its microenvironment properties. [49][50][51][52][53][54] There are different strategies of procedures for the treatment of skin injuries. Therapeutic strategies for skin healing…”

Comprehensive Review of Hybrid Collagen and Silk Fibroin for Cutaneous Wound Healing

“…The excellent porous structure indirectly influences the swelling ratio characteristic, which in turn regulates the transfer of waste and nutrition in and out of the scaffold [ 34 ]. As a result, these characteristics assist in the biological fixation at the wound bed, contributing to the dynamic wound-healing mechanism [ 35 ].…”