From:  Engineering the microenvironment: advanced biomaterials for humanized in vitro immunotoxicology and carcinogenicity assessment

 Engineering biomaterial properties to control the cellular microenvironment.

PropertyHow to control itKey techniques for controlImpact on cell behavior
PorosityPolymer concentration
Crosslinker ratio/type
Porogen (e.g., salt, sugar) leaching
Gas foaming
Freeze-drying (cryogelation)
Electrospinning (fiber spacing)
3D bioprinting (strand deposition)
Particulate leaching
Solvent casting
Nutrient/waste diffusion: high porosity enhances transport.
Cell migration/invasion: Pore size dictates if cells can infiltrate.
Vascularization: critical for promoting blood vessel ingrowth.
TopographyMaster mold fabrication (lithography)
Fiber alignment (electrospinning)
Surface patterning
Scaffold architecture design
Soft lithography
Micro/nano-patterning
Electrospinning
3D bioprinting
Cell alignment: grooves/fibers guide cell orientation (e.g., neurites, muscle cells).
Focal adhesion: nanoscale features alter integrin binding and signaling.
Migration: contact guidance directs cell movement.
StiffnessPolymer concentration
Crosslinking density (UV intensity, time, initiator concentration)
Polymer choice (e.g., PEG vs. alginate)
Tunable hydrogels (PAAm, PEGDA)
Hybrid systems (e.g., GelMA)
Dynamic crosslinking
Stem cell differentiation: Soft matrices (~0.1–1 kPa) promote neurogenesis; stiffer matrices (~10 kPa) promote osteogenesis.
Cancer progression: increased stiffness can promote invasion and EMT.
Cell spreading: Stiffer substrates typically promote greater cell spreading and traction.