Abstract

Due to great clinical need, research where different biomaterials are tested as 3D scaffolds for skin tissue engineering has increased. In vitro studies use a cell suspension that is simply pipetted onto the material and cultured until the cells migrate and proliferate within the 3D scaffold, which does not mimic the in vivo reality. Our aim was to engineer a novel biomimetic in vitro model that mimics the natural cell infiltration process occurring in wound healing, thus offering a realistic approach when pre-screening and testing new skin substitutes. Our model consists of porous membrane cell culture inserts coated with gelatin and seeded with human dermal fibroblasts, inside which two different commercially available dermal substitutes were placed. Several features relevant to the wound healing process (matrix contraction, cell infiltration and proliferation, integration of the biomaterial with the surrounding tissue, and secretion of exogenous cytokines and growth factors) were evaluated. Our results showed that cells spontaneously infiltrate the materials and that our engineered model is able to induce and detect subtle differences between different biomaterials. The model allows for room for improvements or “adds-on” and miniaturization and can contribute to the development of functional and efficient skin substitutes for burns and chronic wounds.

Highlights

  • Over the last two decades, there has been a significant increase in the number of studies in which different biomaterials are tested as 3D scaffolds in tissue engineering, and skin substitutes have not been an exception [1]

  • For the purpose of this study, we were interested in investigating whether differences in the secretion of exogenous cytokines and growth factors commonly involved in the process of wound secretion of exogenous cytokines and growth factors commonly involved in the process of wound healing could be observed between the two different groups

  • Our aim was to engineer a novel biomimetic in vitro model that mimics the natural cell infiltration process into scaffolds occurring during wound healing, offering a realistic approach when testing novel skin biomaterials

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Summary

Introduction

Over the last two decades, there has been a significant increase in the number of studies in which different biomaterials are tested as 3D scaffolds in tissue engineering, and skin substitutes have not been an exception [1]. The current range of skin substitutes is as numerous as the possible combinations of their characteristics, since these are not mutually exclusive. These characteristics include, but are not limited to, cellularity (acellular or cellular), layering (single layer or bilayer), replaced region (epidermis, dermis, or both), materials used (natural, synthetic, or both), and permanence (temporary or permanent) [1,2]. The current form of static in vitro study is far from the in vivo reality and can lead to incorrect assumptions pertaining to the in vivo outcomes of scaffold implantation, such as integration, cellularization, and contraction [4]

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