In vitro loading models for tendon mechanobiology

Abstract

Tendons are the connective tissue responsible for transferring force from muscles to bones. A key factor in tendon development, maturation, repair, and degradation is its biomechanical environment. Understanding tendon mechanobiology is essential for the development of injury prevention strategies, rehabilitation protocols and potentially novel treatments in tendon injury and degeneration. Despite the simple overall loading on tendon tissue, cells within the tissue in vivo experience a much more complex mechanical environment including tension, compression and shear forces. This creates a substantial challenge in the establishment of in vitro loading models of the tendon. This article reviews multiple loading models used for the study of tendon mechanobiology and summarizes the main findings. Although impressive progress has been achieved in the functionality and mimicry of in vitro loading models, an ideal platform is yet to be developed. Multidisciplinary approaches and collaborations will be the key to unveiling the tendon mechanobiology. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:566-575, 2018.

3D uniaxial mechanical stimulation induces tenogenic differentiation of tendon‐derived stem cells through a PI3K/AKT signaling pathway

“…As the in situ loading of tendon cells is predominantly comprised of tension with some minor shear force and compression, current tendon mechanobiology studies mainly focus on the effect of tension on tendon cells. We had previously summarized and analyzed different tensile strains used in various models and studies and found that 4-6% strain is the most physiologically relevant range, which induces an anabolic effect on tendon cells (19). The loading regime (6% tensile strain, 0.25 Hz, 8 h/d, 6 d) used in the current study was optimized in our previous studies (10,16).…”

“…Rice et al (24) had previously reported differential effects of uniaxial and biaxial strain on mesenchymal stem cells in a vascular differentiation model. However, many tendon studies continue to be performed based on these 2 platforms (19). In particular, even though the biaxial loading provided by the Flexcell system is not fully uniform, nonetheless, it remains a widely used platform in mechanobiology studies.…”

“…Firstly, we examined the protein expression and activation status of AKT, ERK, and Connexin 43. AKT and ERK are key downstream effectors of many cellular signaling pathways, including those involved in musculoskeletal responses (19), and Connexin 43 is a gap junction protein that is modulated during changes to cell-cell adhesions (20,21). The expression of Connexin 43 was increased by mechanical stimulation in both 2D loading systems ( Fig.…”

The mechanobiology of tendon fibroblasts under static and uniaxial cyclic load in a 3D tissue engineered model mimicking native extracellular matrix

“…Cellular deformation in the tendon is an indication that the TF acutely adapt to the mechanical forces, demonstrating mechanical dynamism (Arnoczky et al, ). There are numbers of studies that have been performed under uniaxial and biaxial load (Giannopoulos et al, ; T. Wang et al, ). However, in this study, we had applied constant static load and cyclic to a collagen lattice mimicking NT for 24 hr and monitored force generation in the real time, which had provided us cytomechanical with quantitative cell physiological data, and the similarity between tFPCL static and tFPCL cyclic is that, in both conditions, cells were able to sense mechanical tension, which resulted in the phenomenon called “mechanical adaption” (Brown et al, ).…”

Musculoskeletal mechanobiology: A new era for MechanoMedicine

“…With this goal in mind, we are pleased to introduce this special issue in Musculoskeletal Mechanobiology. This special issue begins with several outstanding reviews that provide updates on the significance of mechanobiology in musculoskeletal research involving cartilage, tendon, muscle and bone, [1][2][3][4][5][6][7][8][9][10] and that span topics from the role of candidate mechanosensors and chemical mediators, 1,5,9,10 in vitro and in vivo models of tissue injury and repair, 3,4 and supporting technologies. 6,7 The majority of original articles following the review papers are related to the mechanobiology of bone and cartilage, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] tissues whose physical regulation have traditionally garnered intensive research focus, followed by complementary research papers in areas of growing prominence: Ligaments, intervertebral discs, and stem cells.…”