The Collagen-Based Medical Device MD-Tissue Acts as a Mechanical Scaffold Influencing Morpho-Functional Properties of Cultured Human Tenocytes

Cells. 2020 Dec 8;9(12):2641. doi: 10.3390/cells9122641.

Abstract

Mechanotransduction is the ability of cells to translate mechanical stimuli into biochemical signals that can ultimately influence gene expression, cell morphology and cell fate. Tenocytes are responsible for tendon mechanical adaptation converting mechanical stimuli imposed during mechanical loading, thus affecting extracellular matrix homeostasis. Since we previously demonstrated that MD-Tissue, an injectable collagen-based medical compound containing swine-derived collagen as the main component, is able to affect tenocyte properties, the aim of this study was to analyze whether the effects triggered by MD-Tissue were based on mechanotransduction-related mechanisms. For this purpose, MD-Tissue was used to coat Petri dishes and cytochalasin B was used to deprive tenocytes of mechanical stimulation mediated by the actin cytoskeleton. Cell morphology, migration, collagen turnover pathways and the expression of key mechanosensors were analyzed by morphological and molecular methods. Our findings confirm that MD-Tissue affects collagen turnover pathways and favors cell migration and show that the MD-Tissue-induced effect represents a mechanical input involving the mechanotransduction machinery. Overall, MD-Tissue, acting as a mechanical scaffold, could represent an effective medical device for a novel therapeutic, regenerative and rehabilitative approach to favor tendon healing in tendinopathies.

Keywords: YAP/TAZ; actin cytoskeleton; collagen turnover; mechanotransduction; medical device; tendinopathy; tendon; tenocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton
  • Aged
  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Movement / drug effects
  • Cells, Cultured
  • Collagen / chemistry*
  • Collagen Type I / metabolism
  • Cytochalasin B / pharmacology
  • Female
  • Focal Adhesion Kinase 1 / genetics
  • Focal Adhesion Kinase 1 / metabolism
  • Focal Adhesions / metabolism
  • Humans
  • Male
  • Middle Aged
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / genetics
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / metabolism
  • Stress, Mechanical*
  • Swine
  • Tenocytes / cytology
  • Tenocytes / drug effects
  • Tenocytes / metabolism*
  • Tenocytes / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Vinculin / genetics
  • Vinculin / metabolism

Substances

  • Cell Cycle Proteins
  • Collagen Type I
  • Transcription Factors
  • YY1AP1 protein, human
  • Vinculin
  • Cytochalasin B
  • Collagen
  • PLOD2 protein, human
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase
  • Focal Adhesion Kinase 1
  • PTK2 protein, human