Hydrogel scaffolds asin vitromodels to study fibroblast activation in wound healing and disease

Abstract

Wound healing results from complex signaling between cells and their environment in response to injury. Fibroblasts residing within the extracellular matrix (ECM) of various connective tissues are critical for matrix synthesis and repair. Upon injury or chronic insult, these cells activate into wound-healing cells, called myofibroblasts, and repair the damaged tissue through enzyme and protein secretion. However, misregulation and persistence of myofibroblasts can lead to uncontrolled accumulation of matrix proteins, tissue stiffening, and ultimately disease. Extracellular cues are important regulators of fibroblast activation and have been implicated in their persistence. Hydrogel-based culture models have emerged as useful tools to examine fibroblast response to ECM cues presented during these complex processes. In this Mini-Review, we will provide an overview of these model systems, which are built upon naturally-derived or synthetic materials, and mimic relevant biophysical and biochemical properties of the native ECM with different levels of control. Additionally, we will discuss the application of these hydrogel-based systems for the examination of fibroblast function and fate, including adhesion, migration, and activation, as well as approaches for mimicking both static and temporal aspects of extracellular environments. Specifically, we will highlight hydrogels that have been used to investigate the effects of matrix rigidity, protein binding, and cytokine signaling on fibroblast activation. Last, we will describe future directions for the design of hydrogels to develop improved synthetic models that mimic the complex extracellular environment.

Adaptable Fast Relaxing Boronate‐Based Hydrogels for Probing Cell–Matrix Interactions

“…By incorporating various biochemical, biophysical, and mechanical cues into a single system, hydrogels provide a powerful in vitro model to probe and understand the fundamentals of cell‐niche interactions2 and to provide information for testing hypotheses related to developmental and disease‐related processes 3, 4…”

Engineering approaches to study fibrosis in 3-D in vitro systems

“…Of particular interest in designing these scaffold systems are three features that comprise the etiological backbone of fibrosis: 1) ECM composition, 2) TGF-β1 presence, and 3) mechanical stiffness (Figure 1). The use of biomaterials to study fibrosis-related behaviors has been broadly reviewed elsewhere [9•,10], while herein we focus on recent biological discoveries related to the three aforementioned features in fibrosis, advancements in the design of engineered 3-D platforms for studying these phenomena, and how this work may be combined with other emerging engineering-based approaches to further our understanding and treatment of fibrosis.…”

Synthesis of highly interconnected 3D scaffold from Arothron stellatus skin collagen for tissue engineering application

“…The wound dressing material should have the structural integrity to promote growth and proliferation of fibroblasts for the formation of new extracellular matrix (ECM), which can contribute significantly by producing collagen and fibronectin for the healing of the wound [2,3]. The collagen has interesting properties that serve as a natural substrate for cell attachment and proliferation, which, in turn, acts as a good matrix for tissue engineering and wound dressing application [4].…”