A Novel Core-Shell Hydrogel 3D Model for Studying Macrophage Mechanosensing and Foreign Body Giant Cell Formation.
| Title: | A Novel Core-Shell Hydrogel 3D Model for Studying Macrophage Mechanosensing and Foreign Body Giant Cell Formation. |
|---|---|
| Authors: | Mahanty M; Department of Nutrition and Food Science, University of Maryland, College Park, MD, 20742, USA.; Ou W; Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.; Zhu X; Department of Veterinary Medicine, University of Maryland, College Park, MD, 20742, USA.; Bromberg JS; University of Maryland School of Medicine, Baltimore, MD, 21201, USA.; He X; Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.; Rahaman SO; Department of Nutrition and Food Science, University of Maryland, College Park, MD, 20742, USA. |
| Source: | Advanced healthcare materials [Adv Healthc Mater] 2026 Jan; Vol. 15 (3), pp. e01614. Date of Electronic Publication: 2025 Sep 20. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 101581613 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2192-2659 (Electronic) Linking ISSN: 21922640 NLM ISO Abbreviation: Adv Healthc Mater Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Weinheim : Wiley-VCH, 2012- |
| MeSH Terms: | Macrophages*/metabolism ; Macrophages*/cytology ; Hydrogels*/chemistry ; Hydrogels*/pharmacology ; Giant Cells, Foreign-Body*/metabolism ; Giant Cells, Foreign-Body*/cytology ; Mechanotransduction, Cellular*; TRPV Cation Channels/metabolism ; TRPV Cation Channels/genetics ; Actins/metabolism ; Animals ; Mice |
| Abstract: | The foreign body response (FBR) to biomaterials is primarily driven by macrophages. At implant sites, macrophages often fuse into destructive foreign body giant cells (FBGCs), yet FBGC-targeted treatments for FBR remain elusive. To fill this knowledge gap, a novel microscale core-shell hydrogel 3D model is developed using heterogeneous alginate-collagen microcapsules with varying matrix stiffness to culture macrophages. This 3D model more closely replicates in vivo conditions. This model is further used to investigate the effects of stiffness and TRPV4 (transient receptor potential vanilloid 4) on FBGC formation. Stiffer 3D hydrogel robustly enhances FBGC formation and F-actin production in wild-type macrophages compared to softer hydrogel, with IL4 and GMCSF priming amplifying these effects. Crucially, TRPV4-null macrophages exhibit reduced FBGC formation and F-actin production, underscoring TRPV4's role in mechanosensing. Further, the N-terminal residues 1-130 of TRPV4 are identified as critical for FBGC formation and F-actin generation. RNA-seq data reveal that TRPV4 modulates inflammatory, fibrotic, and mechanosensitive gene expression in macrophages in 3D environments, offering insights into how TRPV4 governs FBR. Overall, the data establish this 3D model as a powerful tool for biomaterials research and highlight TRPV4 as a key player in macrophage mechanosensing and FBGC formation in 3D condition.; (© 2025 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.) |
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| Grant Information: | R01 AI172086 United States AI NIAID NIH HHS; R01 EB024556 United States EB NIBIB NIH HHS |
| Contributed Indexing: | Keywords: 3D alginate‐collagen microcapsule; biomaterials; foreign body response; giant cell; macrophages |
| Substance Nomenclature: | 0 (Hydrogels); 0 (TRPV Cation Channels); 0 (Actins); 0 (Trpv4 protein, mouse) |
| Entry Date(s): | Date Created: 20250920 Date Completed: 20260120 Latest Revision: 20260307 |
| Update Code: | 20260307 |
| PubMed Central ID: | PMC12817113 |
| DOI: | 10.1002/adhm.202501614 |
| PMID: | 40974126 |
| Database: | MEDLINE |
Journal Article