Engineered Biomaterial Platforms to Study Fibrosis

Abstract

Many pathologic conditions lead to the development of tissue scarring and fibrosis, which are characterized by the accumulation of abnormal extracellular matrix (ECM) and changes in tissue mechanical properties. Cells within fibrotic tissues are exposed to dynamic microenvironments that may promote or prolong fibrosis, which makes it difficult to treat. Biomaterials have proved indispensable to better understand how cells sense their extracellular environment and are now being employed to study fibrosis in many tissues. As mechanical testing of tissues becomes more routine and biomaterial tools become more advanced, the impact of biophysical factors in fibrosis are beginning to be understood. Herein, fibrosis from a materials perspective is reviewed, including the role and mechanical properties of ECM components, the spatiotemporal mechanical changes that occur during fibrosis, current biomaterial systems to study fibrosis, and emerging biomaterial systems and tools that can further the understanding of fibrosis initiation and progression. This review concludes by highlighting considerations in promoting wide‐spread use of biomaterials for fibrosis investigations and by suggesting future in vivo studies that it is hoped will inspire the development of even more advanced biomaterial systems.

Calcium Signaling Regulates Valvular Interstitial Cell Alignment and Myofibroblast Activation in Fast‐Relaxing Boronate Hydrogels

“…By systematically varying the viscoelastic properties of these hydrogels, the range of viscoelasticity that can be achieved is vast, e.g., tissue specific properties for valvular tissue at different stages of fibrotic and calcific disease progression. [12] For this study, we were interested in the effect that changes in viscoelasticity would have on VIC phenotype, rather than matching the stress relaxation of heart value tissue. Therefore, these stress relaxation values enable us to understand and explore this characteristic under a range of different settings.…”

“…Enhanced collagen deposition during disease progression not only increases the stiffness of extracellular matrix, but also alters its viscoelastic properties. [12,25] Viscoelasticity is a time-dependent mechanical property, and there is a growing appreciation for the role viscoelasticity plays in influencing cell fate decisions. [26][27][28][29][30][31] Healthy heart valves are viscoelastic and can relax up to 30% of applied stresses; [32] however, during the progression of AVS, the ability for the valve to relax stresses dynamically changes.…”

Engineering Biomaterials and Approaches for Mechanical Stretching of Cells in Three Dimensions

“…From the aspects of mechanical stretching, hydrogels can not only transmit stretch forces to the resident cells, forcing cells to stretch, but also respond to mechanical stretch itself via structural remodeling and biochemical molecule regulation, all of which can have profound effects on cell behaviors ( Vader et al, 2009 ; Gaul et al, 2018 ; Liu et al, 2020 ; Pei et al, 2020 ). It is therefore reasonable to include mechanical, structural and biochemical considerations when engineering hydrogels for mechanical stretching of cells in three dimensions ( Figure 3 ; Li et al, 2017 ; Davidson et al, 2020 ).…”

Potential Applications of Microfluidics to Acute Kidney Injury Associated with Viral Infection

“…55 Given the propensity of tubular edema and protein accumulation to progress to renal fibrosis, it seems likely that renal fibrosis could be linked to SARS-CoV-2-induced AKI, potentially involving epithelial-to-mesenchymal transition (EMT) and contributions to fibrosis from tubule cells themselves. 58 Other reviews have discussed microfluidic devices for fibrosis modeling in general 6 or for specific organs, 16 and such platforms could be useful to simulate and investigate renal fibrosis associated with COVID-19. Combinatorial investigations of mechanistic interactions between parenchymal cells, fibroblasts, and individual soluble factors could be done efficiently in µ F platforms to gain a better understanding of these complex interactions in AKI.…”