ArticleScience advances2021
A synthetic mechanogenetic gene circuit for autonomous drug delivery in engineered tissues.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 79 citations in OpenAlex.
- Conductive Hydrogels for Exogenous Sensing and Cell Fate Control.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- 25+ Years of TRPV4: From Discovery to Translational Horizons.Research square · 2026Article
- ToxiTaRGET: a multi-omics database for toxicant-responsive molecular targets.Nature communications · 2026Article
- A damaging mutation in COL6A3 alters the mechanobiologic response of chondrocytes derived from human induced pluripotent stem cells.Stem cell research & therapy · 2026Article
- Traceless Regulation of Genetic Circuitry.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Stem Cell and Cell-Free Strategies for Osteoarthritis: Toward Durable Regenerative Therapies.Stem cells international · 2026Review
- An Organ-on-Chip Platform for Strain-Controlled, Tissue-Specific Compression of Cartilage and Mineralized Osteochondral Interface to Study Mechanical Overloading in Osteoarthritis.Advanced healthcare materials · 2025Article
- Review
- Roles of Piezo1 in chronic inflammatory diseases and prospects for drug treatment (Review).Molecular medicine reports · 2025Review
- Designer mammalian living materials through genetic engineering.Bioactive materials · 2025Review
- Dual-responsive synthetic gene circuit for dynamic biologic drug delivery via inflammatory and circadian signaling pathways.Journal of biological engineering · 2025Review
- Skeletal dysplasia-causing mutations in TRPV4 alter the chondrocyte transcriptomic response to mechanical loading.American journal of physiology. Cell physiology · 2025Article
- A synthetic chronogenetic gene circuit for programmed circadian drug delivery.Nature communications · 2025Article
- Tuning the Response of Synthetic Mechanogenetic Gene Circuits Using Mutations in TRPV4.Tissue engineering. Part A · 2025Article
- A programmable arthritis-specific receptor for guided articular cartilage regenerative medicine.Osteoarthritis and cartilage · 2025Article
- Polyunsaturated fatty acids suppress PIEZO ion channel mechanotransduction in articular chondrocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Implications of mechanosensitive ion channels in the pathogenesis of osteoarthritis: a comprehensive review.Frontiers in cell and developmental biology · 2025Review
- Effect of load reduction on the calcification of rat tibial tuberosity: Focus on calcification factors and chondrocyte mechanosensors.Journal of anatomy · 2025Article
- Harnessing mechanobiology to enhance cell therapy.Mechanobiology in medicine · 2024Article
- Compressive stresses in cancer: characterization and implications for tumour progression and treatment.Nature reviews. Cancer · 2024Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Mechanobiologic signals regulate cellular responses under physiologic and pathologic conditions. Using synthetic biology and tissue engineering, we developed a mechanically responsive bioartificial tissue that responds to mechanical loading to produce a preprogrammed therapeutic biologic drug. By deconstructing the signaling networks induced by activation of the mechanically sensitive ion channel transient receptor potential vanilloid 4 (TRPV4), we created synthetic TRPV4-responsive genetic circuits in chondrocytes. We engineered these cells into living tissues that respond to mechanical loading by producing the anti-inflammatory biologic drug interleukin-1 receptor antagonist. Chondrocyte TRPV4 is activated by osmotic loading and not by direct cellular deformation, suggesting that tissue loading is transduced into an osmotic signal that activates TRPV4. Either osmotic or mechanical loading of tissues transduced with TRPV4-responsive circuits protected constructs from inflammatory degradation by interleukin-1α. This synthetic mechanobiology approach was used to develop a mechanogenetic system to enable long-term, autonomously regulated drug delivery driven by physiologically relevant loading.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.