Journal article
Reciprocal Macrophage-MSC Crosstalk Drives Immunomodulatory and Regenerative Phenotypes in a Mineralized Collagen Scaffold
Journal of biomedical materials research. Part A, v 114(6), e70106
Jun 2026
PMID: 42244308
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Critical sized craniomaxillofacial bone defects do not heal naturally and often exhibit chronic inflammatory responses that restrict regeneration. It is increasingly apparent that biomaterials must facilitate dynamic crosstalk between immune cells, such as macrophages, and osteoprogenitors to resolve inflammation and accelerate regeneration. Here, we evaluate interactions between macrophages in a neutral (M0) or pro-inflammatory (M1) state with mesenchymal stem cells (MSCs) in a basal or licensed state within a mineralized collagen scaffold. We reveal that MSC-macrophage crosstalk influences significant changes in osteoprogenitor cell differentiation and immune cell polarization. Notably, crosstalk between MSCs and macrophages drives an early-stage inflammatory response, which enhances the immunomodulatory activity of MSCs via secretion of IL-6, an effect that is heightened for already licensed MSCs. The presence of macrophages in the co-cultures upregulated osteogenic (ALPL, BMP2, COL1A2, and RUNX2) and angiogenic genes (ANGPT1) in basal MSC groups. Further, MSC-macrophage interactions subsequently drive increased M2-like macrophage polarization as early as 7 days of culture, as indicated by surface marker expression. These findings show that biomaterial scaffolds can be leveraged as mediators of MSC-mediated immunomodulation with an emphasis on achieving early-stage pro-inflammatory phenotypes that drive subsequent macrophage polarization and markers of increased regenerative potency.
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Details
- Title
- Reciprocal Macrophage-MSC Crosstalk Drives Immunomodulatory and Regenerative Phenotypes in a Mineralized Collagen Scaffold
- Creators
- Vasiliki Kolliopoulos - University of Illinois Urbana-ChampaignMaxwell Polanek - University of Illinois Urbana-ChampaignHashni E Vidana Gamage - University of Illinois Urbana-ChampaignMelisande Wong Yan Ling - University of Illinois Urbana-ChampaignAleczandria Tiffany - University of Illinois Urbana-ChampaignErik R Nelson - University of Illinois Urbana-ChampaignKara L Spiller - Drexel UniversityBrendan A C Harley (Corresponding Author) - University of Illinois Urbana-Champaign
- Publication Details
- Journal of biomedical materials research. Part A, v 114(6), e70106
- Publisher
- Wiley
- Number of pages
- 13
- Grant note
- R01 DE030491 / NIDCR NIH HHS R01 HL130037 / NHLBI NIH HHS DGE-174604 / NSF Graduate Research Fellowship R21 DE026582 / NIDCR NIH HHS DGE-1144245 / NSF Graduate Research Fellowship GM070421 / Chemistry-Biology Interface Research Training Program at the University of Illinois R01 AR077858 / NIAMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering and Science; Chemical and Biological Engineering
- Web of Science ID
- WOS:001796710800009
- Other Identifier
- 991022191280104721
UN Sustainable Development Goals (SDGs)
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Source: SDGs in the Output
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Engineering, Biomedical
- Materials Science, Biomaterials