ArticleScience advances2020
Enhancing the regenerative effectiveness of growth factors by local inhibition of interleukin-1 receptor signaling.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 30 citations in OpenAlex.
- A novel vascularized hydrogel by encapsulation of lyophilized platelet-rich fibrin into gelatin methacryloyl hydrogel for bone regeneration.Journal of materials science. Materials in medicine · 2025Article
- The P2X7R/NLRP3 inflammasome axis suppresses enthesis regeneration through inflammatory and metabolic macrophage-stem cell cross-talk.Science advances · 2025Article
- Adhesive and injectable hydrogel microspheres for NRF2-mediated periodontal bone regeneration.International journal of oral science · 2025Article
- Local administration of regulatory T cells promotes tissue healing.Nature communications · 2024Article
- Article
- Early osteoimmunomodulation by mucin hydrogels augments the healing and revascularization of rat critical-size calvarial bone defects.Bioactive materials · 2023Article
- Regulating macrophage-MSC interaction to optimize BMP-2-induced osteogenesis in the local microenvironment.Bioactive materials · 2023Article
- A superior extracellular matrix binding motif to enhance the regenerative activity and safety of therapeutic proteins.NPJ Regenerative medicine · 2023Article
- Stem Cell Membrane-Coated Microribbon Scaffolds Induce Regenerative Innate and Adaptive Immune Responses in a Critical-Size Cranial Bone Defect Model.Advanced materials (Deerfield Beach, Fla.) · 2023Article
- IL-1Ra gene transfer potentiates BMP2-mediated bone healing by redirecting osteogenesis toward endochondral ossification.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Innovative biomaterials for the treatment of periodontal disease.Frontiers in dental medicine · 2023Review
- Modulation of the Activity of Stem and Progenitor Cells by Immune Cells.Stem cells translational medicine · 2022Review
- Restoration of the healing microenvironment in diabetic wounds with matrix-binding IL-1 receptor antagonist.Communications biology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although growth factors (GFs) are key molecules for regenerative medicine, their use has been limited by issues associated with suboptimal delivery systems and incomplete understanding of their signaling dynamics. Here, we explored how proinflammatory signals affect GF regenerative potential. Using bone regeneration in mouse, we found that the regenerative capacity of two clinically relevant GFs (BMP-2 and PDGF-BB) is impaired by interleukin-1 receptor (IL-1R1). Mechanistically, IL-1R1 activation in bone-forming cells desensitizes them to GFs and accelerates senescence. Moreover, administration of the GFs triggers IL-1 release by macrophages. To provide localized and sustained IL-1R1 inhibition, we engineered IL-1R antagonist (IL-1Ra) to bind the extracellular matrix (ECM) very strongly and demonstrate that codelivering GFs with ECM-binding IL-1Ra induces superior regeneration. Thus, we highlight that GF regenerative activity is hindered by proinflammatory signals, and GF-based therapies should integrate immunomodulation. Particularly, ECM-binding IL-1Ra holds clinical translational potential by enhancing efficacy of GF therapies.
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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.