Table 1.

List of important structural and mechanical features investigated in fibrosis platforms, commonly used biomaterials to model these features, and representative experimental outcomes.

Material Features	Biomaterials Investigated	Representative Outcomes
Stiffness	2D: Alginate, HA, PDMS, PEG, PAA	Stiff, relative to normal tissue stiffness, biomaterials: Promote myofibroblast activation [74] and epithelial cell dysfunction [47] Promote decreased mesenchymal cell migration rate [142] Soft biomaterials: Promote fibroblast quiescence and epithelial cell differentiation Promote cell-cell interactions over cell-material interactions
Dimensionality	2D: Alginate, HA, PDMS, PEG, PAA 2.5D: Electrospun Dextran/HA/PEG Fibrin, Collagen 3D: Alginate, Dextran, HA, PEG, Polypeptides, Fibrin, Collagen	2.5D biomaterials (e.g., electrospun and natural fibrillar proteins): Promote cell spreading, unless adhesive area is limited [103] Direct cell morphology with underlying topography (e.g., aligned or random) 3D biomaterials:h Support cell spreading and cell-cell interactions when the hydrogel is degradable or can be remodeled [57,66]
Viscoelasticity	2D: Alginate, HA, PAA, PDMS, PEG 3D: Alginate, HA, PEG	Viscoelastic biomaterials: Reduce cell spreading in stiff environments, while promoting spreading in soft environments[100] Promote cell spreading with fast stress relaxation and prevents cell spreading with slow stress relaxation[64,65]
Deformability	2D: Alginate, PEG 2.5D: Electrospun Dextran/HA/PEG, Fibrin, Collagen 3D: Alginate, HA, PEG, Fibrin, Collagen	Extensible (soft) fibrous materials: Support cell spreading[103], myofibroblast activation[99] and cell-cell mechanical coupling through the matrix[109] May locally stiffen through physical remodeling of the matrix[143] Non-extensible (stiff) fibrous materials: Limit physical remodeling of the matrix, as well as reduce cell spreading and myofibroblast activation
Plasticity	2.5D: Electrospun Dextran Fibrin, Collagen 3D: Alginate, Fibrin, Collagen	Plastically deformable hydrogels: Support cell spreading and cell migration through 3D environments[114] Support residual alignment of the matrix after cell remodeling[3]
Porosity	Nanoscale: Alginate, Dextran, HA, PEG Microscale: Alginate, HA Electrospun Dextran/HA/PEG Fibrin, Collagen	Nanoscale porosity: Limits cell migration and spreading unless polymer or crosslinks can be remodeled/degraded Microscale porosity: Permits cell migration and spreading if pores are large enough for cell components (e.g., nucleus, cytoskeleton) to fit through

2D: two-dimensions, 3D: three-dimensions, HA: hyaluronic acid, PEG: polyethylene glycol, PDMS: polydimethylsiloxane, PAA: polyacrylamide