Metabolomic Profiling and Mechanotransduction of Single Chondrocytes Encapsulated in Alginate Microgels
Articular cartilage is comprised of two main components, the extracellular matrix (ECM) and the pericellular matrix (PCM). The PCM helps to protect chondrocytes in the cartilage from mechanical loads, but in patients with osteoarthritis, the PCM is weakened, resulting in increased chondrocyte stress...
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MDPI AG
2022-03-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/5/900 |
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| author | Jacob P. Fredrikson Priyanka P. Brahmachary Ayten E. Erdoğan Zachary K. Archambault James N. Wilking Ronald K. June Connie B. Chang |
| author_facet | Jacob P. Fredrikson Priyanka P. Brahmachary Ayten E. Erdoğan Zachary K. Archambault James N. Wilking Ronald K. June Connie B. Chang |
| author_sort | Jacob P. Fredrikson |
| collection | DOAJ |
| description | Articular cartilage is comprised of two main components, the extracellular matrix (ECM) and the pericellular matrix (PCM). The PCM helps to protect chondrocytes in the cartilage from mechanical loads, but in patients with osteoarthritis, the PCM is weakened, resulting in increased chondrocyte stress. As chondrocytes are responsible for matrix synthesis and maintenance, it is important to understand how mechanical loads affect the cellular responses of chondrocytes. Many studies have examined chondrocyte responses to <i>in vitro</i> mechanical loading by embedding chondrocytes in 3-D hydrogels. However, these experiments are mostly performed in the absence of PCM, which may obscure important responses to mechanotransduction. Here, drop-based microfluidics is used to culture single chondrocytes in alginate microgels for cell-directed PCM synthesis that closely mimics the <i>in vivo</i> microenvironment. Chondrocytes formed PCM over 10 days in these single-cell 3-D microenvironments. Mechanotransduction studies were performed, in which single-cell microgels mimicking the cartilage PCM were embedded in high-stiffness agarose. After physiological dynamic compression in a custom-built bioreactor, microgels exhibited distinct metabolomic profiles from both uncompressed and monolayer controls. These results demonstrate the potential of single cell encapsulation in alginate microgels to advance cartilage tissue engineering and basic chondrocyte mechanobiology. |
| first_indexed | 2024-03-09T20:43:31Z |
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| id | doaj.art-36746f2ed1d64e4284ef2fe269c1bbf4 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:43:31Z |
| publishDate | 2022-03-01 |
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| series | Cells |
| spelling | doaj.art-36746f2ed1d64e4284ef2fe269c1bbf42023-11-23T22:51:58ZengMDPI AGCells2073-44092022-03-0111590010.3390/cells11050900Metabolomic Profiling and Mechanotransduction of Single Chondrocytes Encapsulated in Alginate MicrogelsJacob P. Fredrikson0Priyanka P. Brahmachary1Ayten E. Erdoğan2Zachary K. Archambault3James N. Wilking4Ronald K. June5Connie B. Chang6Department of Chemical & Biological Engineering, Montana State University, P.O. Box 173920, Bozeman, MT 59717, USADepartment of Mechanical & Industrial Engineering, Montana State University, P.O. Box 173800, Bozeman, MT 59717, USADepartment of Chemical & Biological Engineering, Montana State University, P.O. Box 173920, Bozeman, MT 59717, USADepartment of Mechanical & Industrial Engineering, Montana State University, P.O. Box 173800, Bozeman, MT 59717, USADepartment of Chemical & Biological Engineering, Montana State University, P.O. Box 173920, Bozeman, MT 59717, USADepartment of Mechanical & Industrial Engineering, Montana State University, P.O. Box 173800, Bozeman, MT 59717, USADepartment of Chemical & Biological Engineering, Montana State University, P.O. Box 173920, Bozeman, MT 59717, USAArticular cartilage is comprised of two main components, the extracellular matrix (ECM) and the pericellular matrix (PCM). The PCM helps to protect chondrocytes in the cartilage from mechanical loads, but in patients with osteoarthritis, the PCM is weakened, resulting in increased chondrocyte stress. As chondrocytes are responsible for matrix synthesis and maintenance, it is important to understand how mechanical loads affect the cellular responses of chondrocytes. Many studies have examined chondrocyte responses to <i>in vitro</i> mechanical loading by embedding chondrocytes in 3-D hydrogels. However, these experiments are mostly performed in the absence of PCM, which may obscure important responses to mechanotransduction. Here, drop-based microfluidics is used to culture single chondrocytes in alginate microgels for cell-directed PCM synthesis that closely mimics the <i>in vivo</i> microenvironment. Chondrocytes formed PCM over 10 days in these single-cell 3-D microenvironments. Mechanotransduction studies were performed, in which single-cell microgels mimicking the cartilage PCM were embedded in high-stiffness agarose. After physiological dynamic compression in a custom-built bioreactor, microgels exhibited distinct metabolomic profiles from both uncompressed and monolayer controls. These results demonstrate the potential of single cell encapsulation in alginate microgels to advance cartilage tissue engineering and basic chondrocyte mechanobiology.https://www.mdpi.com/2073-4409/11/5/900chondrocytesmicrogelsmicrofluidicsmechanotransductionosteoarthritispericellular matrix |
| spellingShingle | Jacob P. Fredrikson Priyanka P. Brahmachary Ayten E. Erdoğan Zachary K. Archambault James N. Wilking Ronald K. June Connie B. Chang Metabolomic Profiling and Mechanotransduction of Single Chondrocytes Encapsulated in Alginate Microgels Cells chondrocytes microgels microfluidics mechanotransduction osteoarthritis pericellular matrix |
| title | Metabolomic Profiling and Mechanotransduction of Single Chondrocytes Encapsulated in Alginate Microgels |
| title_full | Metabolomic Profiling and Mechanotransduction of Single Chondrocytes Encapsulated in Alginate Microgels |
| title_fullStr | Metabolomic Profiling and Mechanotransduction of Single Chondrocytes Encapsulated in Alginate Microgels |
| title_full_unstemmed | Metabolomic Profiling and Mechanotransduction of Single Chondrocytes Encapsulated in Alginate Microgels |
| title_short | Metabolomic Profiling and Mechanotransduction of Single Chondrocytes Encapsulated in Alginate Microgels |
| title_sort | metabolomic profiling and mechanotransduction of single chondrocytes encapsulated in alginate microgels |
| topic | chondrocytes microgels microfluidics mechanotransduction osteoarthritis pericellular matrix |
| url | https://www.mdpi.com/2073-4409/11/5/900 |
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