Tendon tissue engineering: biomechanical considerations

Abstract

Engineered soft tissue products—both tendon and ligament—have gained tremendous interest in regenerative medicine as alternatives to autograft and allograft treatments due to their potential to overcome limitations such as pain and donor site morbidity. Tendon engineered grafts have focused on the replication of native tendon tissue composition and architecture in the form of scaffolds using synthetic or natural biomaterials seeded with cells and factors. However, these approaches suffer due to static culture environments that fail to mimic the dynamic tissue environment and mechanical forces required to promote tenogenic differentiation of cultured cells. Mechanical stimulation is sensed by cellular mechanosensors such as integrins, focal adhesion kinase, and other transmembrane receptors which promote tenogenic gene expression and synthesis of tendon extracellular matrix components such as Type I collagen. Thus, it is imperative to apply biological and biomechanical aspects to engineer tendon. This review highlights the origin of tendon tissue, its ability to sense forces from its microenvironment, and the biological machinery that helps in mechanosensation. Additionally, this review focuses on use of bioreactors that aid in understanding cell-microenvironment interactions and enable the design of mechanically competent tendon tissue. We categorize these bioreactors based on functional features, sample size/type, and loading regimes and discuss their application in tendon research. The objective of this article is to provide a perspective on biomechanical considerations in the development of functional tendon tissue.

Biomechanical and Histological Results of Dual-Suspensory Reconstruction Using Banded Tendon Graft to Bridge Massive Rotator Cuff Tears in a Chronic Rabbit Model

“…Mechanical stimuli have been reported to be key factors in regulating cell orientation and collagen maturity, organization, and arrangement. 15,26,32 When a banded graft is used to restore the force chain of a damaged rotator cuff, the tensile stress typical along the graft in the suspensory technique might promote graft healing to the rotator cuff tendons and the bone tunnel. 9,17,25,49 With regard to the graft type selected for the dual-suspensory technique, the comparative advantages of the PT graft were identified in this study.…”

In Vitro Cellular Strain Models of Tendon Biology and Tenogenic Differentiation

“…Tendons are hypocellular structures that largely consist of water and extracellular matrix (ECM), with water making up 55–70% of the tissue mass. ( Jaiswal et al, 2020 ). ECM is predominantly composed of various types of collagen protein molecules.…”

“…Viscoelastic materials demonstrate different mechanical properties depending on the rate of loading ( Woo et al, 2000 ; Robi et al, 2013 ). One characteristic of viscoelastic materials such as tendons is creep, the deformation of a material in response to constant load ( Jaiswal et al, 2020 ). Creep test or “fatigue” test is used to demonstrate response of tendon to continuous or repetitive loading ( Wang et al, 2018a ).…”

The Lack of a Representative Tendinopathy Model Hampers Fundamental Mesenchymal Stem Cell Research

“…These reactors, however, lack vascularization, as the static presence of culture medium is not representative for in vivo blood flow. Additionally, culture medium is often individually provided per sample, limiting the inter-sample repeatability ( Jaiswal et al, 2020 ). In the bioreactor of Altman et al, BM-MSCs seeded onto collagen I gel matrices were grown in 12 individual tubes in between two anchors (2 cm apart) for ligament tissue engineering.…”

“…The variety within these studies complicates translational research and hampers scientific progress ( Beldjilali-Labro et al, 2018 ). For a universal tendon model, an optimal bioreactor with a multiple-chamber, multiple-sample set-up should be designed and used across laboratories, since different experimental conditions and appropriate controls are required ( Jaiswal et al, 2020 ). The stretch-perfusion bioreactors are the most advanced and the most suitable for this application, but a universal loading protocol is lacking.…”