Development of immunocompetent full thickness skin tissue constructs to model skin fibrosis for high-throughput drug screening.

IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Yi Wei Lim, Russell Quinn, Kapil Bharti, Marc Ferrer, Hoda Zarkoob, Min Jae Song
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引用次数: 0

Abstract

The lack of the immune component in most of the engineered skin models remains a challenge to study the interplay between different immune and non-immune cell types of the skin. Immunocompetent humanin vitroskin models offer potential advantages in recapitulatingin vivolike behavior which can serve to accelerate translational research and therapeutics development for skin diseases. Here we describe a three-dimensional human full-thickness skin (FTS) equivalent incorporating polarized M1 and M2 macrophages from human peripheral CD14+monocytes. This macrophage-incorporated FTS model demonstrates discernible immune responses with physiologically relevant cytokine production and macrophage plasticity under homeostatic and lipopolysaccharide stimulation conditions. M2-incorporated FTS recapitulates skin fibrosis phenotypes with transforming growth factor-β1 treatment as reflected by significant collagen deposition and myofibroblast expression, demonstrating a M2 potentiation effect. In conclusion, we successfully biofabricated an immunocompetent FTS with functional macrophages in a high-throughput (HT) amenable format. This model is the first step towards a HT-assay platform to develop new therapeutics for skin diseases.

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来源期刊
Biofabrication
Biofabrication ENGINEERING, BIOMEDICAL-MATERIALS SCIENCE, BIOMATERIALS
CiteScore
17.40
自引率
3.30%
发文量
118
审稿时长
2 months
期刊介绍: Biofabrication is dedicated to advancing cutting-edge research on the utilization of cells, proteins, biological materials, and biomaterials as fundamental components for the construction of biological systems and/or therapeutic products. Additionally, it proudly serves as the official journal of the International Society for Biofabrication (ISBF).
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