Development of the Mechanical Properties of Engineered Skin Substitutes After Grafting to Full-Thickness Wounds

Abstract

Engineered skin substitutes (ESSs) have been reported to close full-thickness burn wounds but are subject to loss from mechanical shear due to their deficiencies in tensile strength and elasticity. Hypothetically, if the mechanical properties of ESS matched those of native skin, losses due to shear or fracture could be reduced. To consider modifications of the composition of ESS to improve homology with native skin, biomechanical analyses of the current composition of ESS were performed. ESSs consist of a degradable biopolymer scaffold of type I collagen and chondroitin-sulfate (CGS) that is populated sequentially with cultured human dermal fibroblasts (hF) and epidermal keratinocytes (hK). In the current study, the hydrated biopolymer scaffold (CGS), the scaffold populated with hF dermal skin substitute (DSS), or the complete ESS were evaluated mechanically for linear stiffness (N/mm), ultimate tensile load at failure (N), maximum extension at failure (mm), and energy absorbed up to the point of failure (N-mm). These biomechanical end points were also used to evaluate ESS at six weeks after grafting to full-thickness skin wounds in athymic mice and compared to murine autograft or excised murine skin. The data showed statistically significant differences (p <0.05) between ESS in vitro and after grafting for all four structural properties. Grafted ESS differed statistically from murine autograft with respect to maximum extension at failure, and from intact murine skin with respect to linear stiffness and maximum extension. These results demonstrate rapid changes in mechanical properties of ESS after grafting that are comparable to murine autograft. These values provide instruction for improvement of the biomechanical properties of ESS in vitro that may reduce clinical morbidity from graft loss.

Development of regenerative and flexible fibroin‐based wound dressings

“…This variability gives rise to a wide range of reported mechanical properties, including ultimate tensile strength, which ranges from approximately 1 to 50 MPa . These values matched those of native skin, but the specific case of wound dressings also involves the necessity to realize a flexible device that can adapt the shape to the body (Table ). From a microbiology point of view, the addition of glucose was also evaluated in terms of potential energy source for microorganisms and no negative effect was observed on the glucose‐modified film.…”

Methodologies in creating skin substitutes

“…As we are unsure what an identical skin substitute should resemble, comparing it histologically in vitro is one method, while understanding that there are significant changes to skin substitutes’ genetic expression and mechanical properties in in vivo settings compared to in vitro [24,25]. In order to do this, it is important to understand the basic skin layers and their functions.…”

Skin movement, wound repair and development of engineered skin

“…The mechanical properties of skin (providing and resisting stretch and elasticity) arise primarily from the composition and organization of the extracellular matrix (ECM) in the dermis [derived primarily from the collagen fibres and their morphology, organization and cross‐link density (S5)] . ECM including elastic fibres and proteoglycans influences activity and function of fibroblasts as they adapt to the stiffness of their cytoskeleton to that of their substrate , (S6–S7).…”

“…mechanically tested an engineered skin substitute (ESS) containing human cells at 2 weeks of incubation in vitro and at 6 weeks after grafting to a full‐thickness wound in athymic mice. Mechanical tests were conducted on collagen–glycosaminoglycan scaffold (CGS), dermal skin substitute (DSS), ESS, grafted ESS, autografts and native mouse skin . Several factors found to contribute to ESS mechanical strength included synthesis of new ECM and degradation of scaffold, cellular replication, differentiation and tissue morphogenesis.…”