Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Low back pain is a leading cause of disability worldwide, often attributed to intervertebral disc (IVD) degeneration with loss of the functional nucleus pulposus (NP). Regenerative strategies utilizing biomaterials and stem cells are promising for NP repair. Human NP tissue is highly viscoelastic, relaxing stress rapidly under deformation. However, the impact of tissue-specific viscoelasticity on the activities of adipose-derived stem cells (ASC) remains largely unexplored. Here, we investigated the role of matrix viscoelasticity in regulating ASC differentiation for IVD regeneration. Viscoelastic alginate hydrogels with stress relaxation time scales ranging from 100 s to 1000s were developed and used to culture human ASCs for 21 days. Our results demonstrated that the fast-relaxing hydrogel significantly enhanced ASCs long-term cell survival and NP-like extracellular matrix secretion of aggrecan and type-II collagen. Moreover, gene expression analysis revealed a substantial upregulation of the mechanosensitive ion channel marker TRPV4 and NP-specific markers such as SOX9, HIF-1α, KRT18, CDH2 and CD24 in ASCs cultured within the fast-relaxing hydrogel, compared to slower-relaxing hydrogels. These findings highlight the critical role of matrix viscoelasticity in regulating ASC behavior and suggest that viscoelasticity is a key parameter for novel biomaterials design to improve the efficacy of stem cell therapy for IVD regeneration. STATEMENT OF SIGNIFICANCE: Systematically characterized the influence of tissue-mimetic viscoelasticity on ASC. NP-mimetic hydrogels with tunable viscoelasticity and tissue-matched stiffness. Long-term survival and metabolic activity of ASCs are substantially improved in the fast-relaxing hydrogel. The fast-relaxing hydrogel allows higher rate of cell protrusions formation and matrix remodeling. ASC differentiation towards an NP-like cell phenotype is promoted in the fast-relaxing hydrogel, with more CD24 positive expression indicating NP committed cell fate. The expression of TRPV4, a molecular sensor of matrix viscoelasticity, is significantly enhanced in the fast-relaxing hydrogel, indicating ASC sensing matrix viscoelasticity during cell development. The NP-specific ECM secretion of ASC is considerably influenced by matrix viscoelasticity, where the deposition of aggrecan and type-II collagen are significantly enhanced in the fast-relaxing hydrogel.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.actbio.2024.04.017 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sp1 mechanotransduction regulates breast cancer cell invasion in response to multiple tumor-mimicking extracellular matrix cues.
bioRxiv
March 2025
Department of Mechanical Engineering, University of California, Santa Barbara, Santa Barbara, CA, USA.
Breast cancer progression is marked by extracellular matrix (ECM) remodeling, including increased stiffness, faster stress relaxation, and elevated collagen levels. In vitro experiments have revealed a role for each of these factors to individually promote malignant behavior, but their combined effects remain unclear. To address this, we developed alginate-collagen hydrogels with independently tunable stiffness, stress relaxation, and collagen density.
View Article and Find Full Text PDFEngineered basement membrane mimetic hydrogels to study mammary epithelial morphogenesis and invasion.
bioRxiv
March 2025
University of California, Santa Barbara, Department of Molecular, Cellular, and Developmental Biology.
Reconstituted basement membrane (rBM) products like Matrigel are widely used in 3D culture models of epithelial tissues and cancer. However, their utility is hindered by key limitations, including batch variability, xenogenic contaminants, and a lack of tunability. To address these challenges, we engineered a 3D basement membrane (eBM) matrix by conjugating defined extracellular matrix (ECM) adhesion peptides (IKVAV, YIGSR, RGD) to an alginate hydrogel network with precisely tunable stiffness and viscoelasticity.
View Article and Find Full Text PDFFast-Relaxing Hydrogels Promote Pancreatic Adenocarcinoma Cell Aggressiveness through Integrin β1 Signaling.
Biomacromolecules
February 2025
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United States.
Article Synopsis
- Pancreatic ductal adenocarcinoma (PDAC) is characterized by a rigid extracellular matrix (ECM) that has specific properties like high stiffness and a quick ability to relax from stress, which this study aims to replicate using gelatin-based hydrogels.
- The researchers created these hydrogels with varying stiffness and stress relaxation by manipulating the cross-linking methods and materials, allowing them to better mimic the conditions found in PDAC tissues.
- Experiments showed that the fast-relaxing hydrogels promoted PDAC cell growth and other cancer traits, and blocking a certain protein (integrin β1) changed tumor behavior, suggesting integrin β1 could be a potential target for improving cancer treatment
Viscoelastic hydrogels regulate adipose-derived mesenchymal stem cells for nucleus pulposus regeneration.
Acta Biomater
May 2024
Department of Biomedical Engineering, McGill University, 3775 Rue University, Montréal, QC H3A 2B4, Canada; Department of Mechanical Engineering, McGill University, 817 Sherbrooke Street West, Montréal, QC H3A 0C3, Canada; Department of Surgery, McGill University, 1650 Cedar Avenue, Montréal, QC
Low back pain is a leading cause of disability worldwide, often attributed to intervertebral disc (IVD) degeneration with loss of the functional nucleus pulposus (NP). Regenerative strategies utilizing biomaterials and stem cells are promising for NP repair. Human NP tissue is highly viscoelastic, relaxing stress rapidly under deformation.
View Article and Find Full Text PDFFast-relaxing hydrogels with reversibly tunable mechanics for dynamic cancer cell culture.
Biomater Adv
May 2024
Department of Biomedical Engineering, Purdue School of Engineering & Technology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA; Indiana University Simon Comprehensive Cancer Center, Indian
The mechanics of the tumor microenvironment (TME) significantly impact disease progression and the efficacy of anti-cancer therapeutics. While it is recognized that advanced in vitro cancer models will benefit cancer research, none of the current engineered extracellular matrices (ECM) adequately recapitulate the highly dynamic TME. Through integrating reversible boronate-ester bonding and dithiolane ring-opening polymerization, we fabricated synthetic polymer hydrogels with tumor-mimetic fast relaxation and reversibly tunable elastic moduli.
View Article and Find Full Text PDF