ArticleJournal of biomedical materials research. Part A2012
The effects of substrate stiffness on the in vitro activation of macrophages and in vivo host response to poly(ethylene glycol)-based hydrogels.
Article in Journal of biomedical materials research. Part A, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 222 papers, 1 of them a synthesis that pooled it.
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Who cites it
222 citing papers in PubMed, 1 synthesis or guideline pooled it, 459 citations in OpenAlex.
- Macrophage mechanobiology: from sensing to disease.Frontiers in immunology · 2026Pooled it
- Trial
- Engineering Multilayer Poly(ethylene glycol) Hydrogels via Off-Stoichiometry Thiol-Ene Chemistry.ACS applied polymer materials · 2026Article
- Rational design of immunological programs for functional regenerative niches.Materials today. Bio · 2026Review
- Review
- Diminished fibrotic encapsulation and comparable physicochemical properties of poly (styrene-Frontiers in bioengineering and biotechnology · 2026Article
- PIEZO1 in Immune Cells: From Force to Function.Results and problems in cell differentiation · 2026Review
- Human Endometrial Extracellular Matrix Hydrogel Facilitated Endometrial Mesenchymal Stem Cells for Endometrial Regeneration.Advanced healthcare materials · 2026Article
- A Novel Core-Shell Hydrogel 3D Model for Studying Macrophage Mechanosensing and Foreign Body Giant Cell Formation.Advanced healthcare materials · 2026Article
- Exploring Matrix Stiffness-Related Gene in Periodontitis: A Comprehensive Multidataset Analysis.Mediators of inflammation · 2026Article
- Harnessing stromal vascular fraction-based therapies for wound healing: Mechanisms, synergies, and clinical translation.Regenerative therapy · 2025Review
- The Immobilization of Hyaluronic Acid in 3D Hydrogel Scaffolds Modulates Macrophage Polarization.Advanced biology · 2025Article
- Zwitterionic hydrogel designs for conducting polymers enable bioelectronics with suppressed foreign body responses.bioRxiv : the preprint server for biology · 2025Article
- Immunomodulatory bioadhesive technologies.Biomaterials · 2025Review
- Topographical Patterning of Cell-Repellent Interfaces for Immune-Stealth Implantable Electronics via Multiphoton Ablation Lithography.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Research Progress on Biomaterials with Immunomodulatory Effects in Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- 3D-Printed Microfluidic-Based Cell Culture System With Analysis to Investigate Macrophage Activation.Electrophoresis · 2025Article
- Macrophage Polarization Profiling in Dynamic Culture System.Cellular and molecular bioengineering · 2025Article
- Damage Associated Molecular Patterns (DAMPs) Mediate the Foreign Body Response to Poly(ethylene glycol) Diacrylate Hydrogels via Toll like Receptors.ACS biomaterials science & engineering · 2025Article
- The foreign body response to biomaterial implants is reduced by co-inhibition of TLR2 and TLR4.Acta biomaterialia · 2025Article
162 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Poly(ethylene glycol) (PEG) hydrogels, modified with RGD, are promising platforms for cell encapsulation and tissue engineering. While these hydrogels offer tunable mechanical properties, the extent of the host response may limit their in vivo applicability. The overall objective was to characterize the effects of hydrogel stiffness on the in vitro macrophage response and in vivo host response. We hypothesized that stiffer substrates induce better attachment, adhesion, and increased cell spreading, which elevates the macrophage classically activated phenotype and leads to a more severe foreign body reaction (FBR). PEG-RGD hydrogels were fabricated with compressive moduli of 130, 240, and 840 kPa, and the same RGD concentration. Hydrogel stiffness did not impact macrophage attachment, but elicited differences in cell morphology. Cells retained a round morphology on 130 kPa substrates, with localized and dense F-actin and localized α(V) integrin stainings. Contrarily, cells on stiffer substrates were more spread, with filopodia protruding from the cell, a more defined F-actin, and greater α(V) integrin staining. When stimulated with lipopolysaccharide, macrophages had a classical activation phenotype, with increased expression of TNF-α, IL-1β, and IL-6, however the degree of activation was significantly reduced with the softest hydrogels. A FBR ensued in response to all hydrogels when implanted subcutaneously in mice, but 28 days postimplantation the layer of macrophages at the implant surface was significantly lower in the softest hydrogels. In conclusion, hydrogels with lower stiffness led to reduced macrophage activation and a less severe and more typical FBR, and therefore are more suited for in vivo tissue engineering applications.
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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.