Journal
ACTA BIOMATERIALIA
Volume 9, Issue 7, Pages 7209-7217Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2013.04.008
Keywords
Bone repair/regeneration; Fibrinogen; Immune response; In vivo test; Inflammation
Funding
- FEDER funds through the Programa Operacional Factores de Competitividade - COMPETE
- Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia [PEst-C/SAU/LA0002/2011, PTDC/SAU-BEB/099954/2008]
- FCT-POPH [SFRH/BPD/48533/2008, SFRH/BPD/37090/2007, SFRH/BD/37582/2007]
- FCT-POPH-FSE (Ciencia)
- Fundação para a Ciência e a Tecnologia [PTDC/SAU-BEB/099954/2008] Funding Source: FCT
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Designing new biomaterials that can modulate the inflammatory response instead of attempting just to reduce it constitutes a paradigm change in regenerative medicine. This work aimed to investigate the capacity of an immunomodulatory biomaterial to enhance bone regeneration. For that purpose we incorporated a molecule with well-established pro-inflammatory and pro-healing roles, fibrinogen, in chitosan scaffolds. Two different incorporation strategies were tested, leading to concentrations of 0.54 +/- 0.10 mg fibrinogen g(-1) scaffold immediately upon adsorption (Fg-Sol), and 0.34 +/- 0.04 mg fibrinogen g(-1) scaffold after washing (Fg-Ads). These materials were implanted in a critical size bone defect in rats. At two months post-implantation the extent of bone regeneration was examined by histology and the systemic immune response triggered was evaluated by determining the percentages of myeloid cells, T and B lymphocytes in the draining lymph nodes. The results obtained indicate that the fibrinogen incorporation strategy conditioned the osteogenic capacity of biomaterials. Fg-Ads scaffolds led to more bone formation, and the presence of Fg stimulated angiogenesis. Furthermore, animals implanted with Fg-Ads scaffolds showed significant increases in the percentages of B lymphocytes and myeloid cells in the draining lymph nodes, while levels of T lymphocytes were not significantly different. Finally, a significant increase in TGF-beta was detected in the plasma of animals implanted with Fg-Ads. Taken together the results presented suggest a potential correlation between the elicited immune response and biomaterial osteogenic performance. (c) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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