The Role of Mechanical Loading in Ligament Tissue Engineering

Abstract

Tissue-engineered ligaments have received growing interest as a promising alternative for ligament reconstruction when traditional transplants are unavailable or fail. Mechanical stimulation was recently identified as a critical component in engineering load-bearing tissues. It is well established that living tissue responds to altered loads through endogenous changes in cellular behavior, tissue organization, and bulk mechanical properties. Without the appropriate biomechanical cues, new tissue formation lacks the necessary collagenous organization and alignment for sufficient load-bearing capacity. Therefore, tissue engineers utilize mechanical conditioning to guide tissue remodeling and improve the performance of ligament grafts. This review provides a comparative analysis of the response of ligament and tendon fibroblasts to mechanical loading in current bioreactor studies. The differential effect of mechanical stimulation on cellular processes such as protease production, matrix protein synthesis, and cell proliferation is examined in the context of tissue engineering design.

Influence of Shear Stress in Perfusion Bioreactor Cultures for the Development of Three-Dimensional Bone Tissue Constructs: A Review

“…In addition to bone, mechanical stimuli have been shown to influence the differentiation of other tissues in the body; for example, cyclic distension for the formation of arteries, [105][106][107] dynamic compressive loading for the formation of cartilage, [108][109][110][111] and uniaxial strain or axial compression/tension and torsion for ligament growth. 112 Directing cells toward an angiogenic (endothelial cell) lineage using shear stress is no exception. Similarly to bone, nonhuman [113][114][115][116][117][118][119][120][121][122][123] and human [124][125][126][127][128] cell lines have been studied, with the source of the progenitor cell lines being different to the bone studies.…”

What We Should Know Before Using Tissue Engineering Techniques to Repair Injured Tendons: A Developmental Biology Perspective

“…63,70 However, little is known about their precise roles. The identification of the signaling pathways that initiate and control the progressive change in structure and function of the tendon at its insertion site is a very high priority.…”

Skeletal Regeneration by Mesenchymal Stem Cells: What Else?

“…iv. Though MSC have been made to express tendon-like phenotype and produce aligned collagen-I, mechanical properties of the neotissue produced could not match those of native tendon unless the cells had been subjected to mechanical stimulation (JuncosaMelvin et al, 2006;Benhardt & Cosgriff-Hernández, 2009). Several types of bioreactors have been developed which allow to apply load uniaxially, in a static or dynamic (cyclical) mode, to seeded constructs (Guo & Spector, 2006;Garvin et al, 2003;Abousleiman et al, 2009).…”

“…An excessive mechanical conditioning has been shown to lead to tendon disorders and matrix degeneration, however; thus, optimal values of those mechanical parameters must be determined (Wang, 2006). Generally, cyclic stress application has resulted in better results than static stresses as regards matrix formation and fibre alignment (Kuo & Tuan, 2008;Benhardt & Cosgriff-Hernández, 2009;Nguyen et al, 2009). Taking into account those concepts, we are currently investigating the potential of human MSCs to differentiate into functional tenocytes.…”