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Interpenetrating Polymer Network Hydrogels with Tunable Viscoelasticity and Proteolytic Cleavability to Direct Stem
Prannoy Seth1, Jens Friedrichs1, Yanuar Dwi Putra Limasale1
1Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, 01069, Dresden, Germany.
Advanced Healthcare Materials
|November 7, 2024
Summary
Engineered hydrogels mimic cellular microenvironments by controlling viscoelasticity and matrix cleavability. This platform enhances stem cell spreading, growth, and pluripotency, offering new methods for cell fate control.
Area of Science:
- Biomaterials Science
- Stem Cell Biology
- Tissue Engineering
Background:
- Cellular microenvironments are dynamic, influenced by extracellular matrix (ECM) properties like viscoelasticity and enzymatic degradation.
- Emulating these dynamic ECM characteristics in synthetic biomaterials is crucial for controlling cell behavior.
- Current synthetic biomaterials often struggle to replicate the complex, tunable nature of native cellular niches.
Purpose of the Study:
- To develop a novel, cell-instructive hydrogel platform capable of precisely controlling microenvironmental parameters.
- To investigate the individual and combined effects of hydrogel viscoelasticity and proteolytic cleavability on stem cell behavior.
- To establish a method for exogenous stem cell fate control using engineered biomaterials.
Main Methods:
- Fabrication of interpenetrating polymer networks (IPNs) using four-armed poly(ethylene glycol) and sulfated glycosaminoglycan (sGAG) heparin.
- Tuning hydrogel properties (stiffness, viscoelasticity, proteolytic cleavability) via chemical or physical cross-linking.
- Culturing human mesenchymal stem cells (hMSCs) and human induced pluripotent stem cell (hiPSC) cysts within the developed hydrogel system.
- Assessing cell morphology, transcriptional activity, cyst formation, growth, and pluripotency maintenance.
Main Results:
- Human mesenchymal stem cells showed increased spreading and YAP transcriptional activity in more viscoelastic and cleavable sGAG-IPN hydrogels.
- Human induced pluripotent stem cell cysts exhibited enhanced lumen formation, growth, and pluripotency maintenance in hydrogels with higher viscoelasticity.
- Inhibition studies confirmed the critical roles of actin dynamics and matrix metalloproteinase activity in hiPSC cyst morphology, modulated by hydrogel viscoelasticity.
Conclusions:
- The developed sGAG-IPN hydrogel platform allows for precise, independent tuning of key microenvironmental parameters.
- Hydrogel viscoelasticity and cleavability significantly influence stem cell behavior, including differentiation potential and morphology.
- This platform provides a powerful tool for controlling stem cell fate and function in regenerative medicine applications.
