4.8 Article

Identification of topographical architectures supporting the phenotype of rat tenocytes

Journal

ACTA BIOMATERIALIA
Volume 83, Issue -, Pages 277-290

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2018.10.041

Keywords

Micro-topography; Tenocytes; Phenotypic maintenance; Machine learning; Cell morphology

Funding

  1. Dutch province of Limburg
  2. European Union's Seventh Framework Programme (FP7/2007-2013) [289720]
  3. European Union's Horizon 2020 Programme (H2020-MSCA- ITN-2015) [676338]

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Tenocytes, the main cell type of the tendon, require mechanical stimuli for their proper function. When the tenocyte environment changes due to tissue damage or by transferring tenocytes from their native environment into cell culture, the signals from the tenocyte niche are lost, leading towards a decline of phenotypic markers. It is known that micro-topographies can influence cell fate by the physical cues they provide. To identify the optimal topography-induced biomechanical niche in vitro, we seeded tenocytes on the TopoChip, a micro-topographical screening platform, and measured expression of the tendon transcription factor Scleraxis. Through machine learning algorithms, we associated elevated Scleraxis levels with topological design parameters. Fabricating micro-topographies with optimal surface characteristics on larger surfaces allowed finding an improved expression of multiple tenogenic markers. However, long-term confluent culture conditions coincided with osteogenic marker expression and the loss of morphological characteristics. In contrast, passaging tenocytes which migrated from the tendon directly on the topography resulted in prolonged elongated morphology and elevated Scleraxis levels. This research provides new insights into how micro-topographies influence tenocyte cell fate, and supports the notion that micro-topographical design can be implemented in a new generation of tissue culture platforms for supporting the phenotype of tenocytes. (C) 2018 Published by Elsevier Ltd on behalf of Acta Materialia Inc.

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