ArticleBiomaterials2015
Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds.
Article in Biomaterials, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 344 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
344 citing papers in PubMed, 1 synthesis or guideline pooled it, 752 citations in OpenAlex.
- Effect of Dimethyloxalylglycine on Stem Cells Osteogenic Differentiation and Bone Tissue Regeneration-A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Advances in 3D bioprinting of immunoregulatory biomaterials for bone regeneration.Materials today. Bio · 2026Review
- Article
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- Engineering the Immune-Stromal Microenvironment: A Design Framework for Regenerative Biomaterials.Cells · 2026Review
- Engineering Smart Scaffolds for Osteomyelitis: Integrating Nanotechnology, Drug Delivery, and Tissue Regeneration-A Narrative Review.Journal of functional biomaterials · 2026Review
- Encoded Cell-Material Interactions to Reroute Cytokine Signaling for Regenerative Medicine.Advanced healthcare materials · 2026Article
- Biochemical and Physicomechanical Cues of Biomaterials Guide Osteogenic Differentiation of Mesenchymal Stem Cells.International journal of molecular sciences · 2026Review
- Enhancing Bone Healing with a Priming Stimulus.Life (Basel, Switzerland) · 2026Article
- Nanoparticle-Enabled Modulation of the Bone Immune Microenvironment for Enhanced Regeneration.Bioengineering (Basel, Switzerland) · 2026Review
- Advanced Functional Wound Dressings in Precision Surgery: Immunometabolic Reprogramming, Bioadaptive Biomaterials, and Intelligent Regenerative Interfaces.International journal of molecular sciences · 2026Review
- Time-sequentially released bilayer sandwich cerium oxide nanoparticles on femtosecond laser-treated zirconia implant surface for enhanced antibacterial and osseointegration capacity.Materials today. Bio · 2026Article
- An immunomodulatory bioactive glass orchestrates early bone healing via coordinated macrophage polarization and osteogenesis-osteolysis balance.Materials today. Bio · 2026Article
- Discovery and Characterization of Interleukin-4-Specific Affibodies for Affinity-Controlled Protein Release and Macrophage Polarization.bioRxiv : the preprint server for biology · 2026Article
- Immunogenicity as a Key Challenge in Tissue Engineering: Toward Clinical Translation.Advanced pharmaceutical bulletin · 2026Article
- The Osteoimmune Axis: Immune-Mechanical Crosstalk in Periodontal Bone Remodeling.Biomolecules · 2026Article
- 3D-bioprinted mesenchymal stem cell-derived exosomes reprogram macrophages via PI3K/AKT to accelerate nerve regeneration.Journal of translational medicine · 2026Article
- Recent progress in immunomodulation-based strategies for bone repair.Regenerative therapy · 2026Review
- Integrated in vivo and in vitro experiments with multi-omics analysis reveal SPP1 drives pancreatic cancer progression.BMC cancer · 2026Article
- 3D Osteoimmune Stem Cell Spheroids with Osteoinduction and Immunomodulation Dual Functionality forACS biomaterials science & engineering · 2026Article
284 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
In normal tissue repair, macrophages exhibit a pro-inflammatory phenotype (M1) at early stages and a pro-healing phenotype (M2) at later stages. We have previously shown that M1 macrophages initiate angiogenesis while M2 macrophages promote vessel maturation. Therefore, we reasoned that scaffolds that promote sequential M1 and M2 polarization of infiltrating macrophages should result in enhanced angiogenesis and healing. To this end, we first analyzed the in vitro kinetics of macrophage phenotype switch using flow cytometry, gene expression, and cytokine secretion analysis. Then, we designed scaffolds for bone regeneration based on modifications of decellularized bone for a short release of interferon-gamma (IFNg) to promote the M1 phenotype, followed by a more sustained release of interleukin-4 (IL4) to promote the M2 phenotype. To achieve this sequential release profile, IFNg was physically adsorbed onto the scaffolds, while IL4 was attached via biotin-streptavidin binding. Interestingly, despite the strong interactions between biotin and streptavidin, release studies showed that biotinylated IL4 was released over 6 days. These scaffolds promoted sequential M1 and M2 polarization of primary human macrophages as measured by gene expression of ten M1 and M2 markers and secretion of four cytokines, although the overlapping phases of IFNg and IL4 release tempered polarization to some extent. Murine subcutaneous implantation model showed increased vascularization in scaffolds releasing IFNg compared to controls. This study demonstrates that scaffolds for tissue engineering can be designed to harness the angiogenic behavior of host macrophages towards scaffold vascularization.
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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.