title: High content imaging in the screening of biomaterial-induced MSC behavior.
abstract: Upon contact with a biomaterial, cells and surrounding tissues respond in a manner dictated by the physicochemical and mechanical properties of the material. Traditionally, cellular responses are monitored using invasive analytical methods that report the expression of genes or proteins. These analytical methods involve assessing commonly used markers for a predefined readout, masking the actual situation induced in the cells. Hence, a broader expression profile of the cellular response should be envisioned, which technically limits up scaling to higher throughput systems. However, it is increasingly recognized that morphometric readouts, obtained non-invasively, are related to gene expression patterns. Here, we introduced distinct surface roughness to three PLA surfaces, by exposure to oxygen plasma of different duration times. The response of mesenchymal stromal cells was compared to smooth untreated PLA surfaces without the addition of differentiation agents. Morphological and genome wide expression profiles revealed underlying cellular changes which was hidden for the commonly used gene markers for osteo-, chondro- and adipogenesis. Using 3 morphometric parameters, obtained by high content imaging, we were able to build a classifier and discriminate between oxygen plasma-induced modified sheets and non-modified PLA sheets where evaluating classical candidates missed this effect. This approach shows the feasibility to use noninvasive morphometric data in high-throughput systems to screen biomaterial surfaces indicating the underlying genetic biomaterial-induced changes.
authors.affiliation: MIRA Institute for Biomedical Technology and Technical Medicine, Department of Tissue Regeneration, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
authors.forename: H V
authors.initials: HV
authors.lastname: Unadkat
authors.forename: N
authors.initials: N
authors.lastname: Groen
authors.forename: J
authors.initials: J
authors.lastname: Doorn
authors.forename: B
authors.initials: B
authors.lastname: Fischer
authors.forename: A M C
authors.initials: AM
authors.lastname: Barradas
authors.forename: M
authors.initials: M
authors.lastname: Hulsman
authors.forename: J
authors.initials: J
authors.lastname: van de Peppel
authors.forename: L
authors.initials: L
authors.lastname: Moroni
authors.forename: J P
authors.initials: JP
authors.lastname: van Leeuwen
authors.forename: M J T
authors.initials: MJ
authors.lastname: Reinders
authors.forename: C A
authors.initials: CA
authors.lastname: van Blitterswijk
authors.forename: J
authors.initials: J
authors.lastname: de Boer
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D005240:Feasibility Studies; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D057054:Molecular Imaging / Q000379:methods*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D020543:Proteome / Q000378:metabolism*; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D011091:Polyesters; D011108:Polymers; D020543:Proteome; D019344:Lactic Acid; C033616:poly(lactide)