Fibrinogen scaffolds with immunomodulatory properties promote in vivo bone regeneration


The hypothesis behind this work is that fibrinogen (Fg), classically considered a pro-inflammatory protein, can promote bone repair/regeneration. Injury and biomaterial implantation naturally lead to an inflammatory response, which should be under control, but not necessarily minimized. Herein, porous scaffolds entirely constituted of Fg (Fg-3D) were implanted in a femoral rat bone defect and investigated at two important time points, addressing the bone regenerative process and the local and systemic immune responses, both crucial to elucidate the mechanisms of tissue remodelling. Fg-3D led to early infiltration of granulation tissue (6 days post-implantation), followed by bone defect closure, including periosteum repair (8 weeks post-injury). In the acute inflammatory phase (6 days) local gene expression analysis revealed significant increases of pro-inflammatory cytokines IL-6 and IL-8, when compared with non-operated animals. This correlated with modified proportions of systemic immune cell populations, namely increased T cells and decreased B, NK and NIT lymphocytes and myeloid cell, including the Mac 1+ (CD18+/CD11b+) subpopulation. At 8 weeks, Fg-3D led to decreased plasma levels of IL-1 beta and increased TGF-beta 1. Thus, our data supports the hypothesis, establishing a link between bone repair induced by Fg-3D and the immune response. In this sense, Fg-3D scaffolds may be considered immunomodulatory biomaterials. (C) 2016 Elsevier Ltd. All rights reserved.




Engineering; Materials Science


Vasconcelos, DM; Goncalves, RM; Almeida, CR; Pereira, IO; Oliveira, MI; Neves, N; Silva, AM; Ribeiro, AC; Cunha, C; Almeida, AR; Ribeiro, CC; Gil, AM; Seebach, E; Kynast, KL; Richter, W; Lamghari, M; Santos, SG; Barbosa, MA

nossos autores


This work was financed by the project (NORTE-01-0145-FEDER-000012), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). AS, DV, MIO, CC were supported by PhD and Post-Doc fellowships SFRH/BD/85968/2012, SFRH/BD/87516/2012, SFRH/BPD/37090/2007, SFRH/BDP/87071/2012, respectively. The NMR work was developed within the scope of the project CICECO-Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (FCT Ref. UID/CTM/50011/2013), financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. AMG also thanks Portuguese National Nuclear Magnetic Resonance Network, supported with FCT funds. The authors thank Griffons, S.A. for supplying thrombin.

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