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Introduction: The immune system plays a vital role in inducing inflammation, tissue repairing and regeneration. Currently, there is an endeavour to investigate the role of macrophages in bone tissue regeneration. It has been elucidated that macrophages can polarise to proinflammatory M1 and anti-inflammatory M2 phenotypes. However, the role of macrophage phenotypes in bone tissue regeneration is not fully understood and needs more investigation.
On the other hand, the interaction of macrophages with an implanted biomaterial is inevitable. It has been acknowledged that the property of implanted biomaterials may cause exacerbated immune response, which leads to the rejection of implants and bone tissue deterioration. Therefore, controlling the macrophage phenotypes by releasing immunomodulatory drugs from the implant for directing the bone tissue regeneration outcomes is the scope of this study.
Methodology: Polycaprolactone (PCL) polymer was alone or mixed with different ratios of poloxamers F127, F68, L31, and surfactants SPAN80 and emulsifying agent. Dexamethasone was added to polymer mixtures as 0.12% (w/w). Polymer inks were printed by a 3D Discovery printer (regenHU, Switzerland) with a dimension of 10 x 10 x 5 mm3. The release of Dexamethasone from 3D printed PCL scaffolds were conducted in PBS at 37⁰C. Afterwards, the immunomodulatory effect of the released drug from 3D printed scaffolds on M1 polarization was evaluated by quantifying Tumour necrosis factor-alpha (TNF-α), IL-6, IL-1β, IL10, CCL-18 cytokines by DuoSet ELISA kit (R&D Systems); also surface markers calprotectin and mannose were stained.
Results: Scaffolds composed of emulsifying agent showed a prolonged release profile up to 30 days with the cumulative release of 80%, on the other hand, scaffolds made of poloxamer and surfactants showed 100% cumulative release of drug within 24h hrs whereas, PCL alone reached 100% of cumulative release in 7 days. The released dose of Dexamethasone from scaffold made of emulsifying agent and PCL alone was reduced the production of TNF-α, IL-6 and IL-1β from Polarized M1 macrophages. Also, it enhanced the expression of CCL-18 and Mannose receptor expression at day 7.
Conclusion: our result demonstrated a prolonged release profile of Dexamethasone from 3D printed PCL scaffolds composed of emulsifying agent compared to other scaffolds. The released dose of Dexamethasone modulated the immune response of macrophages without compromising its viability in vitro.
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