title: Macrophage interactions with polylactic acid and chitosan scaffolds lead to improved recruitment of human mesenchymal stem/stromal cells: a comprehensive study with different immune cells.
abstract: Despite the importance of immune cell-biomaterial interactions for the regenerative outcome, few studies have investigated how distinct three-dimensional biomaterials modulate the immune cell-mediated mesenchymal stem/stromal cells (MSC) recruitment and function. Thus, this work compares the response of varied primary human immune cell populations triggered by different model scaffolds and describes its functional consequence on recruitment and motility of bone marrow MSC. It was found that polylactic acid (PLA) and chitosan scaffolds lead to an increase in the metabolic activity of macrophages but not of peripheral blood mononuclear cells (PBMC), natural killer (NK) cells or monocytes. PBMC and NK cells increase their cell number in PLA scaffolds and express a secretion profile that does not promote MSC recruitment. Importantly, chitosan increases IL-8, MIP-1, MCP-1 and RANTES secretion by macrophages while PLA stimulates IL-6, IL-8 and MCP-1 production, all chemokines that can lead to MSC recruitment. This secretion profile of macrophages in contact with biomaterials correlates with the highest MSC invasion. Furthermore, macrophages enhance stem cell motility within chitosan scaffolds by 44% but not in PLA scaffolds. Thus, macrophages are the cells that in contact with engineered biomaterials become activated to secrete bioactive molecules that stimulate MSC recruitment.
authors.affiliation: i3S-Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal INEB-Instituto de Engenharia Biomédica, Porto, Portugal ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Hugo R
authors.identifier: 0000-0001-7657-7410
authors.initials: HR
authors.lastname: Caires
authors.affiliation: i3S-Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal INEB-Instituto de Engenharia Biomédica, Porto, Portugal Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, s/n, 4200-465 Porto, Portugal.
authors.forename: Tiago
authors.identifier: 0000-0003-3407-6436
authors.initials: T
authors.lastname: Esteves
authors.affiliation: i3S-Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal INEB-Instituto de Engenharia Biomédica, Porto, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Quelhas
authors.affiliation: i3S-Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal INEB-Instituto de Engenharia Biomédica, Porto, Portugal ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Mário A
authors.identifier: 0000-0003-3568-7482
authors.initials: MA
authors.lastname: Barbosa
authors.affiliation: International Center for Numerical Methods in Engineering (CIMNE), Edificio Nexus (103) Carrer del Gran Capità, 2-4, 08034 Barcelona, Spain.
authors.forename: Melba
authors.identifier: 0000-0002-2638-5784
authors.initials: M
authors.lastname: Navarro
authors.affiliation: i3S-Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal INEB-Instituto de Engenharia Biomédica, Porto, Portugal Department of Medical Sciences and Institute for Biomedicine-iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal catalmeida0@gmail.com.
authors.forename: Catarina R
authors.identifier: 0000-0001-6670-6004
authors.initials: CR
authors.lastname: Almeida
mesh_terms: D002465:Cell Movement / Q000276:immunology*; D048271:Chitosan / Q000737:chemistry*; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D011091:Polyesters / Q000737:chemistry*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D016207:Cytokines; D011091:Polyesters; C033616:poly(lactide); D048271:Chitosan
keywords: biomaterials; human; inflammation; mesenchymal stem cell; recruitment; regeneration