title: Adsorbed fibrinogen leads to improved bone regeneration and correlates with differences in the systemic immune response.
abstract: 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±0.10mg fibrinogen g(-1) scaffold immediately upon adsorption (Fg-Sol), and 0.34±0.04mg 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-β1 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.
authors.affiliation: Instituto de Engenharia Biomédica, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. susana.santos@ineb.up.pt
authors.forename: S G
authors.initials: SG
authors.lastname: Santos
authors.forename: M
authors.initials: M
authors.lastname: Lamghari
authors.forename: C R
authors.initials: CR
authors.lastname: Almeida
authors.forename: M I
authors.initials: MI
authors.lastname: Oliveira
authors.forename: N
authors.initials: N
authors.lastname: Neves
authors.forename: A C
authors.initials: AC
authors.lastname: Ribeiro
authors.forename: J N
authors.initials: JN
authors.lastname: Barbosa
authors.forename: R
authors.initials: R
authors.lastname: Barros
authors.forename: J
authors.initials: J
authors.lastname: Maciel
authors.forename: M C L
authors.initials: MC
authors.lastname: Martins
authors.forename: R M
authors.initials: RM
authors.lastname: Gonçalves
authors.forename: M A
authors.initials: MA
authors.lastname: Barbosa
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000276:immunology; D000327:Adsorption; D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects*; D001861:Bone Regeneration / Q000187:drug effects / Q000276:immunology*; D048271:Chitosan / Q000737:chemistry; D004343:Drug Implants / Q000008:administration & dosage; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005340:Fibrinogen / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D007155:Immunologic Factors; D008297:Male; D008422:Materials Testing; D051381:Rats; D017208:Rats, Wistar; D013223:Statistics as Topic; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology* / Q000517:prevention & control*; D054457:Tissue Scaffolds / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D001672:Biocompatible Materials; D004343:Drug Implants; D007155:Immunologic Factors; D005340:Fibrinogen; D048271:Chitosan