Synthetic Materials that Affect the Extracellular Matrix via Cellular Metabolism and Responses to a Metabolic State
In regenerative medicine and tissue engineering, many materials are developed to mimic the extracellular matrix (ECM). However, these ECM-mimicking materials do not yet completely recapitulate the diversity and complexity of biological tissue-specific ECM. In this review, an alternative strategy is...
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| Format: | Article |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2021.742132/full |
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| author | Mireille M.J.P.E. Sthijns Mireille M.J.P.E. Sthijns Clemens A. van Blitterswijk Vanessa L.S. LaPointe |
| author_facet | Mireille M.J.P.E. Sthijns Mireille M.J.P.E. Sthijns Clemens A. van Blitterswijk Vanessa L.S. LaPointe |
| author_sort | Mireille M.J.P.E. Sthijns |
| collection | DOAJ |
| description | In regenerative medicine and tissue engineering, many materials are developed to mimic the extracellular matrix (ECM). However, these ECM-mimicking materials do not yet completely recapitulate the diversity and complexity of biological tissue-specific ECM. In this review, an alternative strategy is proposed to generate ECM, namely synthesizing a material that functions as a drug delivery system, releasing molecules that target cellular metabolic pathways and thereby stimulate the local cells to create their own ECM. This is based on the fact that ECM synthesis, modification, composition, signaling, stiffness, and degradation are modulated by cellular metabolism. Metabolism can be targeted at different levels, ranging from modulating the availability of substrates or co-factors to regulating the activity of essential transcription factors. Depending on the drug of interest, its characteristics, mechanism of action, cellular target, and application, a different drug delivery system should be designed. Metabolic drugs modulating the ECM require cellular uptake for their function, therefore reversible linkers are recommended. Preferably the metabolic modulators are only released when needed, which will be upon a specific metabolic state, a change in ECM stiffness, or ECM remodeling. Therefore, reversible linkers that respond to an environmental stimulus could be incorporated. All in all, a novel strategy is suggested to develop a tissue-specific ECM by generating a synthetic material that releases metabolic molecules modulating the ECM. Various ways to modulate the ECM properties via the metabolism are reviewed and guidelines for the development of these materials are provided. |
| first_indexed | 2024-12-20T18:46:04Z |
| format | Article |
| id | doaj.art-68f9cdb6bf574020ac2f606ad71d17cd |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-20T18:46:04Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-68f9cdb6bf574020ac2f606ad71d17cd2022-12-21T19:29:43ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852021-10-01910.3389/fbioe.2021.742132742132Synthetic Materials that Affect the Extracellular Matrix via Cellular Metabolism and Responses to a Metabolic StateMireille M.J.P.E. Sthijns0Mireille M.J.P.E. Sthijns1Clemens A. van Blitterswijk2Vanessa L.S. LaPointe3Department of Cell Biology–Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, NetherlandsDepartment of Food Innovation and Health at the Centre of Healthy Eating and Food Innovation, Maastricht University, Maastricht, NetherlandsDepartment of Cell Biology–Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, NetherlandsDepartment of Cell Biology–Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, NetherlandsIn regenerative medicine and tissue engineering, many materials are developed to mimic the extracellular matrix (ECM). However, these ECM-mimicking materials do not yet completely recapitulate the diversity and complexity of biological tissue-specific ECM. In this review, an alternative strategy is proposed to generate ECM, namely synthesizing a material that functions as a drug delivery system, releasing molecules that target cellular metabolic pathways and thereby stimulate the local cells to create their own ECM. This is based on the fact that ECM synthesis, modification, composition, signaling, stiffness, and degradation are modulated by cellular metabolism. Metabolism can be targeted at different levels, ranging from modulating the availability of substrates or co-factors to regulating the activity of essential transcription factors. Depending on the drug of interest, its characteristics, mechanism of action, cellular target, and application, a different drug delivery system should be designed. Metabolic drugs modulating the ECM require cellular uptake for their function, therefore reversible linkers are recommended. Preferably the metabolic modulators are only released when needed, which will be upon a specific metabolic state, a change in ECM stiffness, or ECM remodeling. Therefore, reversible linkers that respond to an environmental stimulus could be incorporated. All in all, a novel strategy is suggested to develop a tissue-specific ECM by generating a synthetic material that releases metabolic molecules modulating the ECM. Various ways to modulate the ECM properties via the metabolism are reviewed and guidelines for the development of these materials are provided.https://www.frontiersin.org/articles/10.3389/fbioe.2021.742132/fullextracellar matrixmetabolismmaterialsregenerative medicinetissue engineering |
| spellingShingle | Mireille M.J.P.E. Sthijns Mireille M.J.P.E. Sthijns Clemens A. van Blitterswijk Vanessa L.S. LaPointe Synthetic Materials that Affect the Extracellular Matrix via Cellular Metabolism and Responses to a Metabolic State Frontiers in Bioengineering and Biotechnology extracellar matrix metabolism materials regenerative medicine tissue engineering |
| title | Synthetic Materials that Affect the Extracellular Matrix via Cellular Metabolism and Responses to a Metabolic State |
| title_full | Synthetic Materials that Affect the Extracellular Matrix via Cellular Metabolism and Responses to a Metabolic State |
| title_fullStr | Synthetic Materials that Affect the Extracellular Matrix via Cellular Metabolism and Responses to a Metabolic State |
| title_full_unstemmed | Synthetic Materials that Affect the Extracellular Matrix via Cellular Metabolism and Responses to a Metabolic State |
| title_short | Synthetic Materials that Affect the Extracellular Matrix via Cellular Metabolism and Responses to a Metabolic State |
| title_sort | synthetic materials that affect the extracellular matrix via cellular metabolism and responses to a metabolic state |
| topic | extracellar matrix metabolism materials regenerative medicine tissue engineering |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2021.742132/full |
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