Controlled M1-to-M2 transition of aged macrophages by calcium phosphate coatings
| Autor: | Iman M. Al-Naggar, Jumana R. Alhamdi, Tao Peng, Kelly L. Hawley, Liisa T. Kuhn, Kara L. Spiller |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Calcium Phosphates
Male Simvastatin Time Factors THP-1 Cells medicine.medical_treatment Biophysics chemistry.chemical_element Bioengineering Inflammation 02 engineering and technology Bone healing Calcium Bone grafting Article Biomaterials Interferon-gamma 03 medical and health sciences Drug Delivery Systems Immune system Coated Materials Biocompatible Bone cell Animals Humans Medicine Cellular Senescence 030304 developmental biology 0303 health sciences Dose-Response Relationship Drug business.industry Macrophages Monocyte 021001 nanoscience & nanotechnology Mice Inbred C57BL Kinetics medicine.anatomical_structure Gene Expression Regulation chemistry Mechanics of Materials Ceramics and Composites Cancer research Bone marrow medicine.symptom 0210 nano-technology business |
| Zdroj: | Biomaterials. 196:90-99 |
| ISSN: | 0142-9612 |
| DOI: | 10.1016/j.biomaterials.2018.07.012 |
| Popis: | Older adults suffer from weakened and delayed bone healing due to age-related alterations in bone cells and in the immune system. Given the interaction between the immune system and skeletal cells, therapies that address deficiencies in both the skeletal and the immune system are required to effectively treat bone injuries of older patients. The sequence of macrophage activation observed in healthy tissue repair involves a transition from a pro-inflammatory state followed by a pro-reparative state. In older patients, inflammation is slower to resolve and impedes healing. The goal of this study was to design a novel drug delivery system for temporal guidance of the polarization of macrophages using bone grafting materials. A biomimetic calcium phosphate coating (bCaP) physically and temporally separated the pro-inflammatory stimulus interferon-gamma (IFNγ) from the pro-reparative stimulus simvastatin (SIMV). Effective doses were identified using a human monocyte line (THP-1) and testing culminated with bone marrow macrophages obtained from old mice. Sequential M1-to-M2 activation was achieved with both cell types. These results suggest that this novel immunomodulatory drug delivery system holds potential for controlling macrophage activation in bones of older patients. |
| Databáze: | OpenAIRE |
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