Sustained Release of Dexamethasone from 3D-Printed Scaffolds Modulates Macrophage Activation and Enhances Osteogenic Differentiation

Majrashi, Majed; Yang, Jing; Ghaemmaghami, Amir; Kotowska, Anna; Hicks, Jacqueline M.; Scurr, David

Abstract

Enhancing osteogenesis via modulating immune cells is emerging as a new approach to address current challenges in repairing bone defects and fractures. However, much remains unknown about the crosstalk between immune cells and osteolineage cells during bone formation. Moreover, biomaterial scaffold-based approaches to effectively modulate this crosstalk to favour bone healing are also lacking. This study is the first to investigate the interactions between macrophages and mesenchymal stem cells (MSCs) in co-cultures with the sustained release of an anti-inflammatory and pro-osteogenesis drug (dexamethasone) from 3D printed scaffolds. We successfully achieved the sustained release of dexamethasone from polycaprolactone (PCL) by adding the excipient-sucrose acetate isobutyrate (SAIB). Dexamethasone was released over 35 days in the 17 nM to 163 nM range. The osteogenic differentiation of MSCs was enhanced by M1 macrophages at early time points. The late-stage mineralisation was dominated by dexamethasone, with little contribution from the macrophages. Besides confirming BMP-2 whose secretion was promoted by both dexamethasone and M1 macrophages as a soluble mediator for enhanced osteogenesis, IL-6 was found to be a possible new soluble factor that mediated osteogenesis in macrophage-MSC co-cultures. The phenotype switching from M1 to M2 was drastically enhanced by the scaffold-released dexamethasone but only marginally by the co-cultured MSCs. Our results offer new insight into macrophage-MSC crosstalk and demonstrate the potential of using drug-release scaffolds to both modulate inflammation and enhance bone regeneration.

Citation

Majrashi, M., Yang, J., Ghaemmaghami, A., Kotowska, A., Hicks, J. M., & Scurr, D. (2023). Sustained Release of Dexamethasone from 3D-Printed Scaffolds Modulates Macrophage Activation and Enhances Osteogenic Differentiation. ACS Applied Materials and Interfaces, 15(49), 56623–56638. https://doi.org/10.1021/acsami.3c09774

• Journal Article Type: Article
• Acceptance Date: Nov 14, 2023
• Online Publication Date: Nov 28, 2023
• Publication Date: Dec 13, 2023
• Deposit Date: Nov 15, 2023
• Publicly Available Date: Nov 29, 2024
• Journal: ACS Applied Materials and Interfaces
• Print ISSN: 1944-8244
• Electronic ISSN: 1944-8252
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 49
• Pages: 56623–56638
• DOI: https://doi.org/10.1021/acsami.3c09774
• Keywords: Tissue engineering, Controlled release, Dexamethasone, 3D printing, Macrophages, Mesenchymal stem cells, Immunomodulation
• Public URL: https://nottingham-repository.worktribe.com/output/27372981
• Publisher URL: https://pubs.acs.org/doi/10.1021/acsami.3c09774