Journal
BIOMATERIALS
Volume 35, Issue 19, Pages 5138-5147Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.03.024
Keywords
Silk; Tropoelastin; Subcutaneous implant; IL-1 beta; Inflammation
Funding
- Lishui Municipality
- National Key Project [2010CB945501, 2010CB912604]
- E-Institutes of Shanghai Municipal Education Commission [E03003]
- Australian Research Council
- Australian Defense Health Foundation
- National Health and Medical Research Council [APP1033079, APP1039072]
- National Institutes of Health [EB014283, HL107503]
- University of Sydney Travel Fellowship
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Blended polymers are used extensively in many critical medical conditions as components of permanently implanted devices. Hybrid protein polymers containing recombinant human tropoelastin and silk fibroin have favorable characteristics as implantable scaffolds in terms of mechanical and biological properties. A firefly luciferase transgenic mouse model was used to monitor real-time IL-1 beta production localized to the site of biomaterial implantation, to observe the acute immune response (up to 5 days) to these materials. Significantly reduced levels of IL-1 beta were observed in silk/tropoelastin implants compared to control silk only implants at 1, 2 and 3 days post-surgery. Subsequently, mice (n = 9) were euthanized at 10 days (10D) and 3 weeks (3W) post-surgery to assess inflammatory cell infiltration and collagen deposition, using histopathology and immunohistochemistry. Compared to control silk only implants, fewer total inflammatory cells were found in silk/tropoelastin (similar to 29% at 10D and similar to 47% at 3W). Also fewer ingrowth cells (similar to 42% at 10D and similar to 63% at 3W) were observed within the silk/tropoelastin implants compared to silk only. Lower IL-6 ( similar to 52%) and MMP-2 ( similar to 84%) (pro-inflammatory) were also detected for silk/tropoelastin at 10 days. After 3 weeks implantation, reduced neovascularization (vWF similar to 43%), fewer proliferating cells (1(167 similar to 58% and PCNA similar to 41%), macrophages (F4/80 similar to 64%), lower IL-10 (similar to 47%) and MMP-9 (similar to 55%) were also observed in silk/tropoelastin materials compared to silk only. Together, these results suggest that incorporation of tropoelastin improves on the established biocompatibility of silk fibroin, uniquely measured here as a reduced foreign body inflammatory response. Crown Copyright (C) 2014 Published by Elsevier Ltd. All rights reserved.
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