Journal article
Chondrogenic Differentiation of Adipose-Derived Stromal Cells in Combinatorial Hydrogels Containing Cartilage Matrix Proteins with Decoupled Mechanical Stiffness
Tissue engineering. Part A, v 20(15-16), pp 2131-2139
01 Aug 2014
PMID: 24707837
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Adipose-derived stromal cells (ADSCs) are attractive autologous cell sources for cartilage repair given their relative abundance and ease of isolation. Previous studies have demonstrated the potential of extracellular matrix (ECM) molecules as three-dimensional (3D) scaffolds for promoting chondrogenesis. However, few studies have compared the effects of varying types or doses of ECM molecules on chondrogenesis of ADSCs in 3D. Furthermore, increasing ECM molecule concentrations often result in simultaneous changes in the matrix stiffness, which makes it difficult to elucidate the relative contribution of biochemical cues or matrix stiffness on stem cell fate. Here we report the development of an ECM-containing hydrogel platform with largely decoupled biochemical and mechanical cues by modulating the degree of methacrylation of ECM molecules. Specifically, we incorporated three types of ECM molecules that are commonly found in the cartilage matrix, including chondroitin sulfate (CS), hyaluronic acid (HA), and heparan sulfate (HS). To elucidate the effects of interactive biochemical and mechanical signaling on chondrogenesis, ADSCs were encapsulated in 39 combinatorial hydrogel compositions with independently tunable ECM types (CS, HA, and HS), concentrations (0.5%, 1.25%, 2.5%, and 5% [w/v]), and matrix stiffness (3, 30, and 90 kPa). Our results show that the effect of ECM composition on chondrogenesis is dependent on the matrix stiffness of hydrogels, suggesting that matrix stiffness and biochemical cues interact in a nonlinear manner to regulate chondrogenesis of ADSCs in 3D. In soft hydrogels (similar to 3 kPa), increasing HA concentrations resulted in substantial upregulation of aggrecan and collagen type II expression in a dose-dependent manner. This trend was reversed in HA-containing hydrogels with higher stiffness (similar to 90 kPa). The platform reported herein could provide a useful tool for elucidating how ECM biochemical cues and matrix stiffness interact together to regulate stem cell fate, and for rapidly optimizing ECM-containing scaffolds to support stem cell differentiation and tissue regeneration.
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Details
- Title
- Chondrogenic Differentiation of Adipose-Derived Stromal Cells in Combinatorial Hydrogels Containing Cartilage Matrix Proteins with Decoupled Mechanical Stiffness
- Creators
- Tianyi Wang - Stanford UniversityJanice H. Lai - Stanford UniversityLi-Hsin Han - Stanford UniversityXinming Tong - Stanford UniversityFan Yang - Stanford University
- Publication Details
- Tissue engineering. Part A, v 20(15-16), pp 2131-2139
- Publisher
- Mary Ann Liebert, Inc
- Number of pages
- 9
- Grant note
- March of Dimes Foundation; March of Dimes Stanford Bio-X interdisciplinary initiative award Singapore A*STAR; Agency for Science Technology & Research (A*STAR)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Mechanical Engineering and Mechanics; Drexel University
- Web of Science ID
- WOS:000340846500009
- Scopus ID
- 2-s2.0-84906542453
- Other Identifier
- 991020100183204721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Cell & Tissue Engineering
- Cell Biology
- Engineering, Biomedical
- Materials Science, Biomaterials