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Functionalized Enzyme-Responsive Biomaterials to Model Tissue Stiffening in vitro
Annalisa Tirella1,2, Giorgio Mattei3, Margherita La Marca4
1BioEngineered Systems Lab, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.
Frontiers in Bioengineering and Biotechnology
|April 24, 2020
Summary
Researchers developed tunable poly(ethylene glycol) hydrogels that mimic soft tissue stiffness. These materials respond to lysyl oxidase (LOx), enabling dynamic changes in the cellular microenvironment for disease modeling.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Cellular Mechanobiology
Background:
- Cellular microenvironment stiffness significantly influences cell behavior.
- Pathophysiological processes often involve changes in extracellular matrix (ECM) stiffness.
- Lysyl oxidase (LOx) is an enzyme implicated in ECM stiffening.
Purpose of the Study:
- To engineer poly(ethylene glycol) (PEG)-based hydrogels with tunable mechanical properties.
- To create LOx-responsive hydrogels that mimic dynamic ECM stiffening.
- To develop 3D in vitro models for studying hepatic tissue mechanobiology.
Main Methods:
- Fabrication of PEG hydrogels with controlled elastic moduli (0.5-4 kPa) via photopolymerization.
- Functionalization of hydrogels with primary amines for LOx-mediated crosslinking.
- Characterization of hydrogel stiffness changes after LOx incubation.
- Encapsulation of HepG2 cells within hydrogels to create 3D in vitro hepatic models.
Main Results:
- Achieved hydrogel elastic moduli in the soft tissue range (0.5-4 kPa).
- Demonstrated LOx-induced increase in hydrogel stiffness (up to 0.5 kPa).
- HepG2 cells maintained viability and function in 3D models for 7 days.
Conclusions:
- Engineered PEG hydrogels possess tunable mechanical properties mimicking soft tissues.
- The LOx-responsive system allows dynamic modulation of hydrogel stiffness.
- These 3D models are suitable for investigating cell mechanobiology and pathological microenvironment changes.
