Mechanical Actuation Systems for the Phenotype Commitment of Stem Cell-Based Tendon and Ligament Tissue Substitutes
- 476 Downloads
High tensile forces transmitted by tendons and ligaments make them susceptible to tearing or complete rupture. The present standard reparative technique is the surgical implantation of auto- or allografts, which often undergo failure.
Currently, different cell types and biomaterials are used to design tissue engineered substitutes. Mechanical stimulation driven by dedicated devices can precondition these constructs to a remarkable degree, mimicking the local in vivo environment. A large number of dynamic culture instruments have been developed and many appealing results collected. Of the cells that have been used, tendon stem cells are the most promising for a reliable stretch-induced tenogenesis, but their reduced availability represents a serious limitation to upscaled production. Biomaterials used for scaffold fabrication include both biological molecules and synthetic polymers, the latter being improved by nanotechnologies which reproduce the architecture of native tendons. In addition to cell type and scaffold material, other variables which must be defined in mechanostimulation protocols are the amplitude, frequency, duration and direction of the applied strain. The ideal conditions seem to be those producing intermittent tension rather than continuous loading. In any case, all physical parameters must be adapted to the specific response of the cells used and the tensile properties of the scaffold. Tendon/ligament grafts in animals usually have the advantage of mechanical preconditioning, especially when uniaxial cyclic forces are applied to cells engineered into natural or decellularized scaffolds. However, due to the scarcity of in vivo research, standard protocols still need to be defined for clinical applications.
KeywordsLigament Mechanical actuation systems Regenerative medicine Stem cells Tendon Tissue engineering
This work has been supported by a Regione Emilia Romagna grant: POR-FESR 2007-2011.
Compliance with Ethical Standards
Conflict of Interest
The authors indicate no potential conflicts of interest.
- 2.Robi, K., Jakob, N., Matevz, K., Matjaz, V. (2013). The physiology of sports injuries and repair processes. In M. Hamlin (Ed.), Current issues in sports and exercise medicine (pp. 43–86). Rijeka, Croatia: InTech. doi: 10.5772/54234.
- 6.Turner, N. J., & Badylak, S. F. (2013). Biologic scaffolds for musculotendinous tissue repair. European Cells & Materials, 25, 130–143.Google Scholar
- 8.Bagnaninchi, P. O., Yang, Y., El Haj, A. J., Maffulli, N. (2007). Tissue engineering for tendon repair. British Journal of Sports Medicine, 41(8), e10; discussion e10.Google Scholar
- 25.Birmingham, E., Niebur, G. L., McHugh, P. E., Shaw, G., Barry, F. P., & McNamara, L. M. (2012). Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche. European Cells & Materials, 23, 13–27.Google Scholar
- 32.Mazzocca, A. D., McCarthy, M. B. R., Chowaniec, D., et al. (2011). Bone marrow–derived mesenchymal stem cells obtained during arthroscopic rotator cuff repair surgery show potential for tendon cell differentiation after treatment with insulin. Arthroscopy, 27(11), 1459–1471.CrossRefPubMedGoogle Scholar
- 46.Ouyang, H. W., Goh, J. C. H., Mo, X. M., Teoh, S. H., & Lee, E. H. (2002). Characterization of anterior cruciate ligament cells and bone marrow stromal cells on various biodegradable polymeric films. Materials Science & Engineering. C, Materials for Biological Applications, 20(1–2), 63–69.CrossRefGoogle Scholar
- 64.Candiani, G., Riboldi, S. A., Sadr, N., et al. (2010). Cyclic mechanical stimulation favors myosin heavy chain accumulation in engineered skeletal muscle constructs. Journal of Applied Biomaterials & Biomechanics, 8(2), 68–75.Google Scholar
- 67.Angelidis, I. K., Thorfinn, J., Connolly, I. D., Lindsey, D., Pham, H. M., & Chang, J. (2010). Tissue engineering of flexor tendons: the effect of a tissue bioreactor on adipoderived stem cell-seeded and fibroblast-seeded tendon constructs. The Journal of Hand Surgery, 35(9), 1466–1472.CrossRefPubMedGoogle Scholar
- 69.Scott, A., Danielson, P., Abraham, T., Fong, G., Sampaio, A. V., & Underhill, T. M. (2011). Mechanical force modulates scleraxis expression in bioartificial tendons. Journal of Musculoskeletal & Neuronal Interactions, 11(2), 124–132.Google Scholar
- 70.Morita, Y., Watanabe, S., Ju, Y., & Xu, B. (2013b). Determination of optimal cyclic uniaxial stretches for stem cell-to-tenocyte differentiation under a wide range of mechanical stretch conditions by evaluating gene expression and protein synthesis levels. Acta of Bioengineering and Biomechanics, 15(3), 71–79.PubMedGoogle Scholar
- 73.Zhang, L., Tran, N., Chen, H. Q., et al. (2008). Time-related changes in expression of collagen types I and III and of tenascin-C in rat bone mesenchymal stem cells under co-culture with ligament fibroblasts or uniaxial stretching. Cell and Tissue Research, 332(1), 101–109.CrossRefPubMedGoogle Scholar
- 74.Kreja, L., Liedert, A., Schlenker, H., et al. (2012). Effects of mechanical strain on human mesenchymal stem cells and ligament fibroblasts in a textured poly(L-lactide) scaffold for ligament tissue engineering. Journal of Materials Science. Materials in Medicine, 23(10), 2575–2582.CrossRefPubMedGoogle Scholar
- 75.Kahn, C. J., Ziani, K., Zhang, Y. M., et al. (2013). Mechanical properties evolution of a PLGA-PLCL composite scaffold for ligament tissue engineering under static and cyclic traction-torsion in vitro culture conditions. Journal of biomaterials science. Polymer Edition, 24(8), 899–911.PubMedGoogle Scholar
- 81.Shearn, J. T., Kinneberg, K. R., Dyment, N. A., et al. (2011). Tendon tissue engineering: progress, challenges, and translation to the clinic. Journal of Musculoskeletal & Neuronal Interactions, 11(2), 163–173.Google Scholar
- 88.Nirmalanandhan, V. S., Juncosa-Melvin, N., Shearn, J. T., et al. (2009). Combined effects of scaffold stiffening and mechanical preconditioning cycles on construct biomechanics, gene expression, and tendon repair biomechanics. Tissue Engineering. Part A, 15(8), 2103–2111.CrossRefPubMedPubMedCentralGoogle Scholar