Abstract
The purpose of this study was to prove the effect of cyclic uniaxial intermittent strain on the mRNA expression of ligament-specific marker genes in human mesenchymal stem cells (MSC) and anterior cruciate ligament-derived fibroblasts (ACL-fibroblasts) seeded onto a novel textured poly(l-lactide) scaffold (PLA scaffold). Cell-seeded scaffolds were mechanically stimulated by cyclic uniaxial stretching. The expression of ligament matrix gene markers: collagen types I and III, fibronectin, tenascin C and decorin, as well as the proteolytic enzymes matrix metalloproteinase MMP-1 and MMP-2 and their tissue specific inhibitors TIMP-1 and TIMP-2 was investigated by analysing the mRNA expression using reverse transcriptase polymerase chain reaction and related to the static control. In ACL-fibroblasts seeded on PLA, mechanical load induced up-regulation of collagen types I and III, fibronectin and tenascin C. No effect of mechanical stimulation on the expression of ligament marker genes was found in undifferentiated MSC seeded on PLA. The results indicated that the new textured PLA scaffold could transfer the mechanical load to the ACL-fibroblasts and improved their ligament phenotype. This scaffold might be suitable as a cell-carrying component of ACL prostheses.
Similar content being viewed by others
References
Laurencin CT, Freeman JW. Ligament tissue engineering: an evolutionary materials science approach. Biomaterials. 2005;26:7530–6.
Pertigliano FA, McAllister DR, Wu BM. Tissue engineering for anterior cruciate ligament reconstruction: a review of current strategies. Arthroscopy. 2006;22:441–51.
Dourte LM, Kuntz A, Soslowsky LJ. Twenty-five years of tendon and ligament research. J Orthop Res. 2008;26:1297–305.
Viera AC, Guedes RM, Marques AT. Development of ligament tissue biodegradable devices: a review. J Biomech. 2009;42:2421–30.
Hogan MV, Bagayoko N, James R, Starnes T, Katz A, Chhabra AB. Tissue engineering solutions for tendon repair. J Am Acad Orthop Surg. 2011;19:134–42.
Shearn JT, Kinneberg KRC, Dyment NA, Galloway MT, Kenter K, Wylie C, Butler DL. Tendon tissue engineering: progress, challenges, and translation to the clinic. J Musculoskelet Neuronal Interact. 2011;11:163–73.
Heckmann L, Schlenker HJ, Fiedler J, Brenner RE, Dauner M, Bergenthal G, Mattes T, Claes L, Ignatius A. Human mesenchymal progenitor cell response to a novel textured poly(l-lactide) scaffold for ligament tissue engineering. J Biomed Mater Res A Appl Biomater. 2007;81B:82–90.
Dunn MG, Liesch JB, Tiku ML, Zawadsky JP. Development of fibroblast-seeded ligament analogs for ACL reconstruction. J Biomed Mater Res. 1995;29:1363–71.
Ge Z, Goh JC, Lee EH. Selection of cell source for ligament tissue engineering. Cell Transplant. 2005;14:573–83.
Lee EH, Hui JH. The potential of stem cells in orthopaedic surgery. J Bone Joint Surg Br. 2006;88:841–51.
Van Eijk F, Saris DB, Riesle J, Willems WJ, Van Blitterswijk CA, Verbaut AJ. Tissue engineering of ligaments: a comparison of bone marrow stromal cells, anterior cruciate ligaments, and skin fibroblasts as cell source. Tissue Eng. 2004;10:893–903.
Yin Z, Chen X, Chen JL, Ouyang HW. Stem cells for tendon tissue engineering and regeneration. Expert Opin Biol Ther. 2010;10:689–700.
Bernhardt HA, Cosgriff-Hernandez EM. The role of mechanical loading in ligament tissue engineering. Tissue Eng Part B. 2009;15:467–75.
Kuo CK, Marturano JE, Tuan RS. Novel strategies in tendon and ligament tissue engineering: advanced biomaterials and regeneration motifs. Sports Med Arthrosc Rehabil Ther Technol. 2010;2:20.
Altman GH, Horan RL, Martin I, Farhadi J, Stark PR, Volloch V, Richmond JC, Vunjak-Novakovic G, Kaplan DL. Cell differentiation by mechanical stress. FASEB J. 2002;16:270–2.
Butler DL, Juncosa-Melvin N, Boivin GP, Galloway MT, Shearn JT, Gooch C, Awad H. Functional tissue engineering for tendon repair: a multidisciplinary strategy using mesenchymal stem cells, bioscaffolds, and mechanical stimulation. J Orthop Res. 2008;26:1–9.
Chen J, Horan RL, Bramono D, Moreau J, Wang Y, Geuss LR, Collette AL, Volloch V, Altman GH. Monitoring mesenchymal stromal cell developmental stage to apply on-time mechanical stimulation for ligament tissue engineering. Tissue Eng. 2006;12:3085–95.
Juncosa-Melvin N, Matlin KS, Holdcraft RW, Nirmalanandhan VS, Butler DL. Mechanical stimulation increase collagen type I and collagen type III gene expression of stem cell-collagen sponge constructs for patella tendon repair. Tissue Eng. 2007;13:1219–26.
Moreau JE, Bramono D, Horan RL, Kaplan DL, Altman GH. Sequential biochemical and mechanical stimulation in the development of tissue-engineered ligaments. Tissue Eng Part A. 2008;14:1161–72.
Petrigliano FA, English CS, Barba D, Esmende S, Wu BM, MacAllister DR. The effects of local bFGF release and uniaxial strain on cellular adaptation and gene expression in a 3D environment: implications for ligament tissue engineering. Tissue Eng. 2007;13:2721–31.
Dürselen L, Dauner M, Hierlemann H, Planck H, Claes LE, Ignatius A. Resorbable polymer fibers for ligament augmentation. J Biomed Mater Res. 2001;58:666–72.
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop DJ, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy. 2006;8:315–7.
Ignatius A, Blessing H, Liedert A, Schmidt C, Neidlinger-Wilke C, Kaspar D, Friemert B, Claes L. Tissue engineering of bone: effects of mechanical strain on osteoblastic cells in type I collagen matrices. Biomaterials. 2005;26:311–8.
Beynnon BD, Fleming BC. Anterior cruciate ligament strain in vivo: a review of previous work. J Biomech. 1998;31:519–25.
Mikuni-Takagaki Y, Suzuki Y, Kawase T, Saito S. Distinct responses of different populations of bone cells to mechanical stress. Endocrinology. 1996;137:2028–35.
Kraft K, Bindslev DA, Melsen B, Abdallah BM, Kassem M, Klein-Nulend J. Mechanosensitivity of dental pulp stem cells is related to their osteogenic maturity. Eur J Oral Sci. 2010;118:29–38.
Chokalingam K, Juncosa-Melvin N, Hunter SA, Gooch C, Frede C, Floret J, Bradica G, Wenstrup R, Butler DL. Tensile stimulation of murine stem cell-collagen sponge constructs increases collagen type I gene expression and linear stiffness. Tissue Eng Part A. 2009;15:2561–70.
Dorski DM, Levenston ME, Temenoff JS. Cyclic tensile culture promotes fibroblastic differentiation of marrow stromal cells encapsulated in poly(ethylene glycol)-based hydrogels. Tissue Eng Part A. 2010;16:3457–66.
Nöth U, Schupp K, Heymer A, Kall S, Jacob F, Schütze N, Bauman B, Barthel T, Eulert J, Hendrich C. Anterior cruciate ligament constructs fabricated from human mesenchymal stem cells in collagen type I hydrogel. Cytotherapy. 2005;7:447–55.
Chen YJ, Huang CH, Lee YT, Chen MH, Young TH. Effects of cyclic stretching on the mRNA expression of tendon/ligament-related and osteoblasts-specific genes in human mesenchymal stem cells. Connect Tissue Res. 2008;49:7–14.
Phinney DG, Koppen G, Righter W, Webster S, Tremain N, Prockop DJ. Donor variation in the growth properties and osteogenic potential of human marrow stromal cells. J Cell Biochem. 1999;75:424–36.
Sidappa R, Licht R, van Blitterswijk C, de Boer J. Donor variation and loss of multipotency during in vitro expansion of human mesenchymal stem cells for bone tissue engineering. J Orthop Res. 2007;25:1029–41.
Hannafin JA, Attia JA, Henshaw R, Warren RF, Bhargava MM. Effect of cyclic strain and plating matrix on cell proliferation and integrin expression by ligament fibroblasts. J Orthop Res. 2006;24:149–56.
Yang G, Crawford RC, Wang JH-C. Proliferation and collagen production of human patellar tendon fibroblasts in response to cyclic uniaxial stretching in serum-free conditions. J Biomech. 2004;37:1543–50.
Zeichen J, van Griensven M, Bosch U. The proliferative response of isolated tendon fibroblasts to cyclic biaxial mechanical strain. Am J Sports Med. 2000;28:888–92.
Kim SG, Akaike T, Sasagaw T, Atomi Y, Kurosawa H. Gene expression of type I and type III collagen by mechanical stretch in anterior cruciate ligament cells. Cell Struct Funct. 2002;27:139–44.
Tetsunaga T, Furumatsu T, Abe N, Nishda K. Mechanical stretch stimulates integrin αVβ3-mediated collagen expression in human anterior cruciate ligament cells. J Biomech. 2009;42:2097–103.
Zhang J, Wang JH-C. Mechanobiological response of tendon stem cells: implications of tendon homeostasis and pathogenesis of tendinopathy. J Orthop Res. 2010;28:639–43.
Lee CH, Shin HJ, Cho IH, Kang YM, Kim IA, Park KD, Shin JW. Nanofiber alignment and direction of mechanical strain affect the ECM production of human ACL fibroblast. Biomaterials. 2005;26:1261–70.
Sawaguchi N, Majima T, Funakoshi T, Shimode K, Harada K, Minami A, Nishimura S. Effect of cyclic tree-dimensional strain on cell prloiferation and collagen synthesis of fibroblasts-seeded chitosan-hyaluronan hybrid polymer fiber. J Orthop Sci. 2010;15:569–77.
Lee J, Guarino V, Gloria A, Ambrosio L, Tae G, Kim YH, Kim HS. Regeneration of Achilles’ tendon: the role of dynamic stimulation for enhanced cell proliferation and mechanical properties. J Biomater Sci. 2010;21:1173–90.
Jiang Y, Liu H, Li H, Wang F, Chen K, Zhou G, Zhang W, Ye M, Cao Y, Liu W, Zou H. A proteomic analysis of engineered tendon formation under dynamic mechanical loading in vitro. Biomaterials. 2011;32:4085–95.
Acknowledgments
The authors wish to thank the Government of Baden-Württemberg for supporting this study in the context of the Network of Excellence for Biomaterials.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kreja, L., Liedert, A., Schlenker, H. et al. Effects of mechanical strain on human mesenchymal stem cells and ligament fibroblasts in a textured poly(l-lactide) scaffold for ligament tissue engineering. J Mater Sci: Mater Med 23, 2575–2582 (2012). https://doi.org/10.1007/s10856-012-4710-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10856-012-4710-7