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Antioxidant and Anti-Senescence Polyvinyl Alcohol-Gallic Acid Supramolecular Hydrogels for Stem Cell Culture
Yiduo Zhou1,2,3, Matías L Picchio4,5,6,7, Yan Nie2,3
1Institute of Chemistry and Biochemistry, Free University of Berlin, 14195, Berlin, Germany.
Abstract:
Replicative senescence presents a significant challenge in mesenchymal stem cell (MSC) expansion due to high reactive oxygen species (ROS) levels generated during culture. Elevated ROS levels lead to oxidative stress, cellular damage, and senescence, limiting the biomedical applications of MSCs. In this study, a supramolecular thermo-reversible hydrogel composed of the natural polyphenolic compound gallic acid (GA) and polyvinyl alcohol (PVA) was designed to scavenge ROS and mitigate MSC senescence. The PVA-GA hydrogel, stabilized by strong hydrogen bonding forces, exhibited an elastic modulus comparable to that of human soft tissue and facilitated the sustained release of GA over 14 days. It enhanced MSC survival, protected against oxidative stress, reduced intracellular ROS levels, diminished mitochondrial damage, and decreased cellular senescence. The hydrogel maintained the multilineage differentiation potential and typical phenotype of MSCs. Additionally, it preserved vascular endothelial growth factor (VEGF) secretion from MSCs under oxidative stress and enhanced their pro-angiogenic effect. The conditioned medium derived from MSCs in the hydrogel group promoted migration and tube formation of human umbilical vein endothelial cells (HUVECs). These findings suggest that the PVA-GA hydrogel holds significant promise for the biomedical applications of MSCs, potentially addressing the challenges posed by oxidative stress and cellular senescence.
Insights
A novel gallic acid-polyvinyl alcohol hydrogel effectively combats reactive oxygen species (ROS) and mesenchymal stem cell (MSC) senescence. This biomaterial enhances MSC function and promotes angiogenesis, paving the way for advanced regenerative medicine applications.
Area of Science:
- Biomaterials Science
- Stem Cell Biology
- Regenerative Medicine
Background:
- Replicative senescence limits mesenchymal stem cell (MSC) expansion due to high reactive oxygen species (ROS) levels.
- Oxidative stress from ROS causes cellular damage and senescence, hindering MSC therapeutic potential.
- Developing strategies to mitigate ROS and MSC senescence is crucial for biomedical applications.
Purpose of the Study:
- To design and evaluate a supramolecular thermo-reversible hydrogel for scavenging ROS and preventing MSC senescence.
- To assess the hydrogel's ability to maintain MSC viability, phenotype, and function under oxidative stress.
- To investigate the hydrogel's impact on MSC-mediated angiogenesis.
Main Methods:
- Fabrication of a gallic acid (GA) and polyvinyl alcohol (PVA) supramolecular hydrogel.
- Characterization of hydrogel properties, including elastic modulus and drug release kinetics.
- In vitro assessment of MSCs cultured within the hydrogel, evaluating survival, ROS levels, mitochondrial damage, senescence, phenotype, and differentiation potential.
- Analysis of vascular endothelial growth factor (VEGF) secretion and pro-angiogenic effects of MSCs.
- Evaluation of conditioned medium's effect on human umbilical vein endothelial cell (HUVEC) migration and tube formation.
Main Results:
- The PVA-GA hydrogel exhibited a suitable elastic modulus and sustained GA release for 14 days.
- Hydrogel culture significantly enhanced MSC survival, reduced intracellular ROS, and mitigated oxidative stress and mitochondrial damage.
- MSCs cultured in the hydrogel showed decreased senescence markers while maintaining their multilineage differentiation potential and phenotype.
- VEGF secretion and pro-angiogenic effects of MSCs were preserved under oxidative stress.
- Conditioned medium from hydrogel-cultured MSCs promoted HUVEC migration and tube formation.
Conclusions:
- The PVA-GA hydrogel effectively scavenges ROS and prevents MSC senescence, preserving critical cellular functions.
- This hydrogel demonstrates significant potential for enhancing MSC-based therapies by improving cell survival and angiogenic capacity.
- The developed hydrogel offers a promising solution for overcoming oxidative stress-related challenges in MSC expansion for biomedical applications.
