title: Surface modification of biomaterials based on high-molecular polylactic acid and their effect on inflammatory reactions of primary human monocyte-derived macrophages: perspective for personalized therapy.
abstract: Polylactic acid (PLA) based implants can cause inflammatory complications. Macrophages are key innate immune cells that control inflammation. To provide higher biocompatibility of PLA-based implants with local innate immune cells their surface properties have to be improved. In our study surface modification technique for high-molecular PLA (MW=1,646,600g/mol) based biomaterials was originally developed and successfully applied. Optimal modification conditions were determined. Treatment of PLA films with toluene/ethanol=3/7 mixture for 10min with subsequent exposure in 0.001M brilliant green dye (BGD) solution allows to entrap approximately 10(-9)mol/cm(2) model biomolecules. The modified PLA film surface was characterized by optical microscopy, SERS, FT-IR, UV and TG/DTA/DSC analysis. Tensile strain of modified films was determined as well. The effect of PLA films modified with BGD on the inflammatory reactions of primary human monocyte-derived macrophages was investigated. We developed in vitro test-system by differentiating primary monocyte-derived macrophages on a coating material. Type 1 and type 2 inflammatory cytokines (TNFα, CCL18) secretion and histological biomarkers (CD206, stabilin-1) expression were analyzed by ELISA and confocal microscopy respectively. BGD-modified materials have improved thermal stability and good mechanical properties. However, BGD modifications induced additional donor-specific inflammatory reactions and suppressed tolerogenic phenotype of macrophages. Therefore, our test-system successfully demonstrated specific immunomodulatory effects of original and modified PLA-based biomaterials, and can be further applied for the examination of improved coatings for implants and identification of patient-specific reactions to implants.
authors.affiliation: Department of Bioengineering and Organic Chemistry, National Research Tomsk Polytechnic University, Russia.
authors.forename: Ksenia S
authors.initials: KS
authors.lastname: Stankevich
authors.affiliation: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Germany; Red Cross Blood Service Baden-Württemberg - Hessen, Mannheim, Germany.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Gudima
authors.affiliation: Department of Bioengineering and Organic Chemistry, National Research Tomsk Polytechnic University, Russia.
authors.forename: Victor D
authors.initials: VD
authors.lastname: Filimonov
authors.affiliation: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Germany; Red Cross Blood Service Baden-Württemberg - Hessen, Mannheim, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Klüter
authors.affiliation: Department of Bioengineering and Organic Chemistry, National Research Tomsk Polytechnic University, Russia.
authors.forename: Evgeniya M
authors.initials: EM
authors.lastname: Mamontova
authors.affiliation: Department of Theoretical and Experimental Physics, National Research Tomsk Polytechnic University, Russia. Electronic address: tverd@tpu.ru.
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Tverdokhlebov
authors.affiliation: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Germany; Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, Russia; Red Cross Blood Service Baden-Württemberg - Hessen, Mannheim, Germany. Electronic address: julia.kzhyshkowska@medma.uni-heidelberg.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Kzhyshkowska
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D055119:Elastic Modulus; D006244:Hardness; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry* / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008422:Materials Testing; D008970:Molecular Weight; D018802:Patient-Centered Care / Q000379:methods; D011091:Polyesters; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013499:Surface Properties; D013718:Tensile Strength
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide)
keywords: Biocompatibility; Cytokines; Macrophages; Monocytes; Polylactic acid; Surface modification