Multimodal analysis of the differential effects of cyclic strain on collagen isoform composition, fibril architecture and biomechanics of tissue engineered tendon

Janvier, Adam J, Pendleton, Emily G, Mortensen, Luke J, Green, Daniel C, Henstock, James R and Canty-Laird, Elizabeth G ORCID: 0000-0001-5041-1316 (2022) Multimodal analysis of the differential effects of cyclic strain on collagen isoform composition, fibril architecture and biomechanics of tissue engineered tendon. JOURNAL OF TISSUE ENGINEERING, 13. 20417314221130486-.

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Official URL: http://dx.doi.org/10.1177/20417314221130486

Abstract

Tendon is predominantly composed of aligned type I collagen, but additional isoforms are known to influence fibril architecture and maturation, which contribute to the tendon's overall biomechanical performance. The role of the less well-studied collagen isoforms on fibrillogenesis in tissue engineered tendons is currently unknown, and correlating their relative abundance with biomechanical changes in response to cyclic strain is a promising method for characterising optimised bioengineered tendon grafts. In this study, human mesenchymal stem cells (MSCs) were cultured in a fibrin scaffold with 3%, 5% or 10% cyclic strain at 0.5 Hz for 3 weeks, and a comprehensive multimodal analysis comprising qPCR, western blotting, histology, mechanical testing, fluorescent probe CLSM, TEM and label-free second-harmonic imaging was performed. Molecular data indicated complex transcriptional and translational regulation of collagen isoforms I, II, III, V XI, XII and XIV in response to cyclic strain. Isoforms (XII and XIV) associated with embryonic tenogenesis were deposited in the formation of neo-tendons from hMSCs, suggesting that these engineered tendons form through some recapitulation of a developmental pathway. Tendons cultured with 3% strain had the smallest median fibril diameter but highest resistance to stress, whilst at 10% strain tendons had the highest median fibril diameter and the highest rate of stress relaxation. Second harmonic generation exposed distinct structural arrangements of collagen fibres in each strain group. Fluorescent probe images correlated increasing cyclic strain with increased fibril alignment from 40% (static strain) to 61.5% alignment (10% cyclic strain). These results indicate that cyclic strain rates stimulate differential cell responses via complex regulation of collagen isoforms which influence the structural organisation of developing fibril architectures.

Item Type:	Article
Uncontrolled Keywords:	Tendon, collagen, cyclic strain, collagen isoforms, collagen fibril
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	08 Nov 2022 15:49
Last Modified:	18 Jan 2023 19:43
DOI:	10.1177/20417314221130486
Open Access URL:	https://doi.org/10.1177/20417314221130486
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3166064