Establishment and application of a fibrosis/scar biospecimen repository and systematic research platform

Abstract

Fibrosis is a pathological outcome of a dysregulated repair response to injury, which can occur in any organ and have devastating effects on hundreds of millions of patients worldwide. However, challenges remain in delineating the complex and dynamic network regulating fibrosis, as well as translating this information into effective anti-fibrotic treatments. A comprehensive understanding of existing methodologies and the development of new research tools are essential for ensuring the transferability of findings from bench to bedside. In this review, we present a framework consisting of a large biospecimen repository that integrates diverse patient cohorts with corresponding clinical data, and a systematic research platform incorporating multiple layers of experimental strategies, primarily focused on skin fibrosis. We summarize current advancements and the applications of various tools for preclinical fibrosis research and examine the limitations of traditional methods used to simulate and investigate biomechanical signals in the fibrotic environment. Importantly, we highlight the strengths of research techniques and translational approaches of varying physiological relevance developed by us over the past decade. Collectively, we emphasize a trend toward more faithfully replicating the functional, structural, and biological complexity of fibrosis while providing high spatio-temporal control over soluble cues and intricate interactions. Our comprehensive overview of methodology paves the way for minimizing batch-to-batch variation and improving the reproducibility of experimental systems.