title: Polymers with tunable toxicity: a reference scale for cytotoxicity testing of biomaterial surfaces.
abstract: A series of copolymers, with varying ratio di-methylamino-ethylmethacrylate (DMAEMA) and methyl-methacrylate (MMA), was designed as a potential scale for cytotoxicity. These copolymers were characterized for toxicity of their surface. The surfaces of washed copolymers display increasing toxicity with increasing DMAEMA content. The toxicity was observed for three different cell-types, namely mouse fibroblasts, human endothelial cells and human osteoblast-like cells. With an increasing toxic surface, cell growth was inhibited as was indicated by the proliferation marker Ki-67. Staining for F-actin revealed that with increasing DMAEMA, cells adopted a more and more round morphology, resulting in decreased surface-contact area. Immuno-staining for phospho-tyrosine or vinculin demonstrated gradual loss of focal adhesions on increasingly toxic surfaces. Surprisingly loss of focal adhesions coincided with an increase in paxillin and vinculin protein, indicating cells try compensating for loss of adhesion. This series of copolymers may have potential as a cytotoxicity scale. They provoke cellular responses ranging from highly toxic to completely non-toxic, with some showing intermediate toxicity.
authors.affiliation: Centre for Biomaterials Research, Department of Medicine, University of Maastricht, Maastricht, The Netherlands. menno.knetsch@bioch.unimaas.nl
authors.forename: Menno L W
authors.initials: ML
authors.lastname: Knetsch
authors.forename: Nadine
authors.initials: N
authors.lastname: Olthof
authors.forename: Leo H
authors.initials: LH
authors.lastname: Koole
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000633:toxicity*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008422:Materials Testing; D008689:Methacrylates / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D009757:Nylons / Q000737:chemistry / Q000633:toxicity; D010006:Osteoblasts / Q000187:drug effects; D011108:Polymers / Q000737:chemistry / Q000633:toxicity*; D019904:Polymethyl Methacrylate / Q000737:chemistry / Q000633:toxicity; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D019394:Ki-67 Antigen; D008689:Methacrylates; C498355:Mki67 protein, mouse; D009757:Nylons; D011108:Polymers; C109846:poly(2-(diethylamino)ethyl methacrylate); D019904:Polymethyl Methacrylate