ArticleBiomaterials2021
Substrate stiffness induces neutrophil extracellular trap (NET) formation through focal adhesion kinase activation.
Article in Biomaterials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 75 citations in OpenAlex.
- Immune-epigenetic convergence in biomaterial-guided tissue regeneration.Materials today. Bio · 2026Article
- Regulating Cells Fate and Function to Facilitate Bone Regeneration via Designing Programmable Bio-Interactive Materials.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Epithelial-Mesenchymal Transition, Immune Response, and Extracellular Matrix Remodelling in Oral Cancer.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026Article
- Airway mucins function as endogenous inhibitors of neutrophil extracellular traps.bioRxiv : the preprint server for biology · 2026Article
- Neutrophil migration in the lung is altered by alveolar collapse and stretch.bioRxiv : the preprint server for biology · 2026Article
- Dual inhibition of neutrophil superoxide generation and elastase releaseRSC advances · 2026Article
- The hypoxic ECM and neutrophils in MIBC immunotherapy resistance.Nature reviews. Urology · 2026Review
- Spatiotemporal dynamics of tumor-associated neutrophils: bridging the gap between cancer progression and immunotherapy.Molecular cancer · 2026Review
- PIEZO1 in Immune Cells: From Force to Function.Results and problems in cell differentiation · 2026Review
- Mechanical Microenvironment in Tumor Immune Evasion: Bidirectional Regulation Between Matrix Stiffness and Immune Cells and Its Therapeutic Implications.International journal of biological sciences · 2026Review
- Mechanotransduction in Shaping Immunity: Pathways, Crosstalk, and Pathophysiological Relevance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Regulation of neutrophil function by the extracellular matrix.Biochemical Society transactions · 2025Review
- Autologous and synthetic vascular grafts trigger different host responses in the anastomotic regions and in the perivascular adipose tissue during the early healing phase.Materials today. Bio · 2025Article
- Irisin regulates integrin αvβ5/FAK/ERK to inhibit neutrophil extracellular traps formation and reduce pancreatic beta-cells pyroptosis in type 2 diabetes mellitus.Diabetology & metabolic syndrome · 2025Article
- The foreign body response to biomaterial implants is reduced by co-inhibition of TLR2 and TLR4.Acta biomaterialia · 2025Article
- Modulating Neutrophil Extracellular Trap FormationACS central science · 2025Article
- Guidance on the assessment of the functionality of biomaterials for periodontal tissue regeneration: Methodologies and testing procedures.Dental materials : official publication of the Academy of Dental Materials · 2025Review
- Neutrophil extracellular traps in ischemic stroke: mechanisms, clinical implications, and therapeutic potential.Frontiers in neurology · 2025Review
- Bioscaffold materials resist infection and promote bone defect repair by regulating neutrophil function.Frontiers in bioengineering and biotechnology · 2025Review
- Extended view on the mechanobiology of fracture healing: interplay between mechanics and inflammation.Frontiers in bioengineering and biotechnology · 2025Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Neutrophils predominate the early inflammatory response to tissue injury and implantation of biomaterials. Recent studies have shown that neutrophil activation can be regulated by mechanical cues such as stiffness or surface wettability; however, it is not known how neutrophils sense and respond to physical cues, particularly how they form neutrophil extracellular traps (NET formation). To examine this, we used polydimethylsiloxane (PDMS) substrates of varying physiologically relevant stiffness (0.2-32 kPa) and examined the response of murine neutrophils to untreated surfaces or to surfaces coated with various extracellular matrix proteins recognized by integrin heterodimers (collagen, fibronectin, laminin, vitronectin, synthetic RGD). Neutrophils on higher stiffness PDMS substrates had increased NET formation and higher secretion of pro-inflammatory cytokines and chemokines. Extracellular matrix protein coatings showed that fibronectin induced the most NET formation and this effect was stiffness dependent. Synthetic RGD peptides induced similar levels of NET formation and pro-inflammatory cytokine release than the full-length fibronectin protein. To determine if the observed NET formation in response to substrate stiffness required focal adhesion kinase (FAK) activity, which is down stream of integrin activation, FAK inhibitor PF-573228 was used. Inhibition of FAK using PF-573228 ablated the stiffness-dependent increase in NET formation and pro-inflammatory molecule secretion. These findings demonstrate that neutrophils regulate NET formation in response to physical and mechanical biomaterial cues and this process is regulated through integrin/FAK signaling.
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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 OpenQuestion graph.