Adsorbed fibrinogen leads to improved bone regeneration and correlates with differences in the systemic immune response

作者：Santos S G^*; Lamghari M; Almeida C R; Oliveira M I; Neves N; Ribeiro A C; Barbosa J N; Barros R; Maciel J; Martins M C L; Goncalves R M; Barbosa M A

来源：Acta Biomaterialia, 2013, 9(7): 7209-7217.

DOI：10.1016/j.actbio.2013.04.008

• Bone repair/regeneration
• Fibrinogen
• Immune response
• In vivo test
• Inflammation

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.

• 出版日期2013-7