title: Incorporation of Mg particles into PDLLA regulates mesenchymal stem cell and macrophage responses.
abstract: In this work, we investigated a new approach to incorporate Mg particles within a PDLLA matrix using a solvent-free commercially available process. PDLLA/Mg composites were manufactured by injection moulding and the effects of Mg incorporated into PDLLA on MSC and macrophage responses were evaluated. Small amounts of Mg particles (≤ 1 wt %) do not cause thermal degradation of PDLLA, which retains its mechanical properties. PDLLA/Mg composites release hydrogen, alkaline products and Mg(2+) ions without changing pH of culture media. Mg-containing materials provide a noncytotoxic environment that enhances MSC viability. Concentration of Mg(2+) ions in extracts of MSCs increases with the increment of Mg content in the composites. Incorporation of Mg particles into PDLLA stimulates FN production, ALP activity, and VEGF secretion in MSCs, an effect mediated by degradation products dissolved from the composites. Degradation products of PDLLA induce an increase in MCP-1, RANTES, and MIP-1α secretion in macrophages while products of composites have minimal effect on these chemokines. Regulation of MSC behavior at the biomaterial's interface and macrophage-mediated inflammatory response to the degradation products is related to the incorporation of Mg in the composites. These findings suggest that including small amounts of Mg particles into polymeric devices can be a valuable strategy to promote osseointegration and reduce host inflammatory response.
authors.affiliation: Departamento de Metalurgia Física, Centro Nacional De Investigaciones Metalúrgicas (CENIM-CSIC), Avda. Gregorio Del Amo 8, Madrid, 28040, Spain.
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Cifuentes
authors.affiliation: Grupo de Fisiopatología Ósea y Biomateriales, Hospital Universitario La Paz-IdiPAZ, Paseo De La Castellana 261, Madrid, 28046, Spain.|CIBER De Bioingeniería, Biomateriales Y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors.forename: Fátima
authors.initials: F
authors.lastname: Bensiamar
authors.affiliation: CIBER De Bioingeniería, Biomateriales Y Nanomedicina (CIBER-BBN), Madrid, Spain.|Departamento De Física Aplicada, Universidad De Extremadura, Avda. De Elvas S/N, Badajoz, 06006, Spain.
authors.forename: Amparo M
authors.initials: AM
authors.lastname: Gallardo-Moreno
authors.affiliation: Department of Mechanical Engineering, Polymer Engineering Center (PEC), University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Tim A
authors.initials: TA
authors.lastname: Osswald
authors.affiliation: Departamento de Metalurgia Física, Centro Nacional De Investigaciones Metalúrgicas (CENIM-CSIC), Avda. Gregorio Del Amo 8, Madrid, 28040, Spain.|CIBER De Bioingeniería, Biomateriales Y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: González-Carrasco
authors.affiliation: Departamento de Química Física, Instituto De Ciencia Y Tecnología De Polímeros ICTP-CSIC, Madrid, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Benavente
authors.affiliation: CIBER De Bioingeniería, Biomateriales Y Nanomedicina (CIBER-BBN), Madrid, Spain.|Departamento De Física Aplicada, Universidad De Extremadura, Avda. De Elvas S/N, Badajoz, 06006, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: González-Martín
authors.affiliation: Grupo de Fisiopatología Ósea y Biomateriales, Hospital Universitario La Paz-IdiPAZ, Paseo De La Castellana 261, Madrid, 28046, Spain.|Departamento de Cirugía Ortopédica y Traumatología, Hospital Universitario La Paz-IdiPAZ, Paseo De La Castellana 261, Madrid 28046, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: García-Rey
authors.affiliation: Grupo de Fisiopatología Ósea y Biomateriales, Hospital Universitario La Paz-IdiPAZ, Paseo De La Castellana 261, Madrid, 28046, Spain.|CIBER De Bioingeniería, Biomateriales Y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Vilaboa
authors.affiliation: Grupo de Fisiopatología Ósea y Biomateriales, Hospital Universitario La Paz-IdiPAZ, Paseo De La Castellana 261, Madrid, 28046, Spain.|CIBER De Bioingeniería, Biomateriales Y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Saldaña
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054405:Chemokine CCL3 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; C111835:CCL2 protein, human; C483024:CCL5 protein, human; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D018946:Chemokine CCL5; D011091:Polyesters; D042461:Vascular Endothelial Growth Factor A; C033616:poly(lactide); D000469:Alkaline Phosphatase; D008274:Magnesium
keywords: composite; macrophage; magnesium; mesenchymal stem cell; polymer