title: Impact of 3-D printed PLA- and chitosan-based scaffolds on human monocyte/macrophage responses: unraveling the effect of 3-D structures on inflammation.
abstract: Recent studies have pointed towards a decisive role of inflammation in triggering tissue repair and regeneration, while at the same time it is accepted that an exacerbated inflammatory response may lead to rejection of an implant. Within this context, understanding and having the capacity to regulate the inflammatory response elicited by 3-D scaffolds aimed for tissue regeneration is crucial. This work reports on the analysis of the cytokine profile of human monocytes/macrophages in contact with biodegradable 3-D scaffolds with different surface properties, architecture and controlled pore geometry, fabricated by 3-D printing technology. Fabrication processes were optimized to create four different 3-D platforms based on polylactic acid (PLA), PLA/calcium phosphate glass or chitosan. Cytokine secretion and cell morphology of human peripheral blood monocytes allowed to differentiate on the different matrices were analyzed. While all scaffolds supported monocyte/macrophage adhesion and stimulated cytokine production, striking differences between PLA-based and chitosan scaffolds were found, with chitosan eliciting increased secretion of tumor necrosis factor (TNF)-α, while PLA-based scaffolds induced higher production of interleukin (IL)-6, IL-12/23 and IL-10. Even though the material itself induced the biggest differences, the scaffold geometry also impacted on TNF-α and IL-12/23 production, with chitosan scaffolds having larger pores and wider angles leading to a higher secretion of these pro-inflammatory cytokines. These findings strengthen the appropriateness of these 3-D platforms to study modulation of macrophage responses by specific parameters (chemistry, topography, scaffold architecture).
authors.affiliation: INEB - Instituto de Engenharia Biomédica, NEWTherapies Group, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. Electronic address: cralmeid@ineb.up.pt.
authors.forename: Catarina R
authors.initials: CR
authors.lastname: Almeida
authors.affiliation: IBEC - Institute for Bioengineering of Catalonia, Biomaterials for Regenerative Group, Baldiri Reixac 15-21, 08028 Barcelona, Spain; CIBER in Bioengineering, Biomaterials and Nanomedicine, Barcelona, Spain.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Serra
authors.affiliation: INEB - Instituto de Engenharia Biomédica, NEWTherapies Group, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
authors.forename: Marta I
authors.initials: MI
authors.lastname: Oliveira
authors.affiliation: IBEC - Institute for Bioengineering of Catalonia, Biomaterials for Regenerative Group, Baldiri Reixac 15-21, 08028 Barcelona, Spain; CIBER in Bioengineering, Biomaterials and Nanomedicine, Barcelona, Spain.
authors.forename: Josep A
authors.initials: JA
authors.lastname: Planell
authors.affiliation: INEB - Instituto de Engenharia Biomédica, NEWTherapies Group, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira n° 228, 4050-313 Porto, Portugal.
authors.forename: Mário A
authors.initials: MA
authors.lastname: Barbosa
authors.affiliation: IBEC - Institute for Bioengineering of Catalonia, Biomaterials for Regenerative Group, Baldiri Reixac 15-21, 08028 Barcelona, Spain; CIBER in Bioengineering, Biomaterials and Nanomedicine, Barcelona, Spain. Electronic address: melba.navarro@gmail.com.
authors.forename: Melba
authors.initials: M
authors.lastname: Navarro
mesh_terms: D000199:Actins / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011091:Polyesters; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D013194:Staining and Labeling; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000199:Actins; D016207:Cytokines; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D048271:Chitosan
keywords: 3-D scaffolds; Human macrophages; Inflammation; Rapid prototyping; Tissue engineering