Physicochemical cues are not potent regulators of human dermal fibroblast trans-differentiation

Christina N M Ryan; Eugenia Pugliese; Naledi Shologu; Diana Gaspar; Peadar Rooney; Md Nahidul Islam; Alan O'Riordan; Manus J Biggs; Matthew D Griffin; Dimitrios I Zeugolis

doi:10.1016/j.bbiosy.2023.100079

Physicochemical cues are not potent regulators of human dermal fibroblast trans-differentiation

Biomater Biosyst. 2023 May 29:11:100079. doi: 10.1016/j.bbiosy.2023.100079. eCollection 2023 Sep.

Authors

Christina N M Ryan^{1

2}, Eugenia Pugliese^{1

2}, Naledi Shologu^{1

2}, Diana Gaspar^{1

2}, Peadar Rooney², Md Nahidul Islam^{2

3

4}, Alan O'Riordan⁵, Manus J Biggs², Matthew D Griffin^{2

3}, Dimitrios I Zeugolis^{1

2

6}

Affiliations

¹ Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Biomedical Sciences Building, University of Galway, Galway, Ireland.
² Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, University of Galway, Galway, Ireland.
³ Regenerative Medicine Institute (REMEDI), School of Medicine, Biomedical Sciences Building, University of Galway, Galway, Ireland.
⁴ Discipline of Biochemistry, School of Natural Sciences, University of Galway, Galway, Ireland.
⁵ Tyndall National Institute, University College Cork (UCC), Cork, Ireland.
⁶ Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Charles Institute of Dermatology, Conway Institute of Biomolecular & Biomedical Research and School of Mechanical & Materials Engineering, University College Dublin (UCD), Dublin, Ireland.

Abstract

Due to their inherent plasticity, dermal fibroblasts hold great promise in regenerative medicine. Although biological signals have been well-established as potent regulators of dermal fibroblast function, it is still unclear whether physiochemical cues can induce dermal fibroblast trans-differentiation. Herein, we evaluated the combined effect of surface topography, substrate rigidity, collagen type I coating and macromolecular crowding in human dermal fibroblast cultures. Our data indicate that tissue culture plastic and collagen type I coating increased cell proliferation and metabolic activity. None of the assessed in vitro microenvironment modulators affected cell viability. Anisotropic surface topography induced bidirectional cell morphology, especially on more rigid (1,000 kPa and 130 kPa) substrates. Macromolecular crowding increased various collagen types, but not fibronectin, deposition. Macromolecular crowding induced globular extracellular matrix deposition, independently of the properties of the substrate. At day 14 (longest time point assessed), macromolecular crowding downregulated tenascin C (in 9 out of the 14 groups), aggrecan (in 13 out of the 14 groups), osteonectin (in 13 out of the 14 groups), and collagen type I (in all groups). Overall, our data suggest that physicochemical cues (such surface topography, substrate rigidity, collagen coating and macromolecular crowding) are not as potent as biological signals in inducing dermal fibroblast trans-differentiation.

Keywords: Collagen type I coating; Fibroblast plasticity; In vitro microenvironment; Macromolecular crowding; Substrate rigidity; Surface topography.