Abstract
Tissue-engineered cartilage (TEC) remains a potential alternative for the repair of articular cartilage defects. However, there has been a significant different between the properties of TEC and those of natural cartilage. Studies have shown that mechanical stimulation such as compressive load can help regulate matrix remodelling in TEC, thus affecting its biomechanical properties. However, the influences of shear induced from the tissue fluid phase have not been well studied and may play an important role in tissue regeneration especially when integrated with the compressive load. Therefore, the aim of this study was to quantitatively investigate the effects of combined loading mechanisms on TEC in vitro. A bespoke biosimulator was built to incorporate the coupled motion of compression, friction and shear. The specimens, encapsulating freshly isolated rabbit chondrocytes in a hydrogel, were cultured within the biosimulator under various mechanical stimulations for 4 weeks, and the tissue activity, matrix contents and the mechanical properties were examined. Study groups were categorized according to different mechanical stimulation combinations, including strain (5–20% at 5% intervals) and frequency (0.25 Hz, 0.5 Hz, 1 Hz), and the effects on tissue behaviour were investigated. During the dynamic culture process, a combined load was applied to simulate the combined effects of compression, friction and shear on articular cartilage during human movement. The results indicated that a larger strain and higher frequency were more favourable for the specimen in terms of the cell proliferation and extracellular matrix synthesis. Moreover, the combined mechanical stimulation was more beneficial to matrix remodelling than the single loading motion. However, the contribution of the combined mechanical stimulation to the engineered cartilaginous tissue matrix was not sufficient to impede biodegradation of the tissue with culture time.
Similar content being viewed by others
Availability of data and material
The materials used in the article are purchased through regular channels, and the experimental data were true and reliable.
References
Sophia Fox AJ, Bedi A, Rodeo SA (2009) The basic science of articular cartilage: structure, composition, and function. Sports Health 1(6):461–468
Hayes DW Jr., Brower RL, John KJ (2001) Articular cartilage. anatomy, injury, and repair. Clin Podiat Med Surg 18(1):35–53
Musumeci G, Loreto C, Castorina S, Imbesi R, Castrogiovanni P (2013) Current concepts in the treatment of cartilage damage. A Rev 118(2):189–203
Murawski CD, Kennedy JG (2013) Operative treatment of osteochondral lesions of the talus. J Bone Joint Surg-Am 95A(11):1045–1054
Lan W, Chen W, Huang D (2019) Research progress on osteochondral tissue engineering. J Biomed Eng 36(3):504–510. https://doi.org/10.7507/1001-5515.201810001
Sahni V, Tibrewal S, Bissell L, Khan WS (2015) The role of tissue engineering in achilles tendon repair: a review. Curr Stem Cell Res Ther 10(1):31–36
Wang YJ, Shang SH, Li CZ (2016) Aligned biomimetic scaffolds as a new tendency in tissue engineering. Curr Stem Cell Res Ther 11(1):3–18
Xu Y, Guo X, Yang S, Li L, Mi S (2018) Construction of bionic tissue engineering cartilage scaffold based on 3D printing and oriented frozen technology. J Biomed Mater Res, Part A 106(6):1664–1676
Temenoff JS, Mikos AG (2000) Review: tissue engineering for regeneration of articular cartilage. Biomaterials 21(5):431–440. https://doi.org/10.1016/s0142-9612(99)00213-6
Wang YZ, Kim UJ, Blasioli DJ, Kim HJ, Kaplan DL (2005) In vitro cartilage tissue engineering with 3D porous aqueous-derived silk scaffolds and mesenchymal stem cells. Biomaterials 26(34):7082–7094
Raghunath J, Salacinski HJ, Sales KM, Butler PE, Seifalian AM (2005) Advancing cartilage tissue engineering: the application of stem cell technology. Curr Opin Biotechnol 16(5):503–509
Tan AR, Hung CT (2017) concise review: mesenchymal stem cells for functional cartilage tissue engineering: taking cues from chondrocyte-based constructs. Stem Cells Translational Medicine 6(4):1295–1303
Niu HJ, Wang Q, Wang YX, Li A, Sun LW, Yan Y, Fan F, Li DY, Fan YB (2012) The study on the mechanical characteristics of articular cartilage in simulated microgravity. Acta Mech Sin 28(5):1488–1493
Chowdhury TT, Bader DL, Shelton JC, Lee DA (2003) Temporal regulation of chondrocyte metabolism in agarose constructs subjected to dynamic compression. Arch Biochem Biophys 417(1):105–111
Ikenoue T, Trindade MCD, Lee MS, Lin EY, Schurman DJ, Goodman SB, Smith RL (2003) Meehanoregulation of human articular chondrocyte aggrecan and type II collagen expression by intermittent hydrostatic pressure in vitro. J Orthop Res 21(1):110–116
De Croos JNA, Dhaliwal SS, Grynpas MD, Pilliar RM, Kandel RA (2006) Cyclic compressive mechanical stimulation induces sequential catabolic and anabolic gene changes in chondrocytes resulting in increased extracellular matrix accumulation. Matrix Biol 25(6):323–331
Wu JZ, Herzog W (2006) Analysis of the mechanical behavior of chondrocytes in unconfined compression tests for cyclic loading. J Biomech 39(4):603–616
Wagner DR, Lindsey DP, Li KW, Tummala P, Chandran SE, Smith RL, Longaker MT, Carter DR, Beaupre GS (2008) Hydrostatic pressure enhances chondrogenic differentiation of human bone marrow stromal cells in osteochondrogenic medium. Ann Biomed Eng 36(5):813–820
Omata S, Sonokawa S, Sawae Y, Murakami T (2012) Effects of both vitamin C and mechanical stimulation on improving the mechanical characteristics of regenerated cartilage. Biochem Biophys Res Commun 424(4):724–729
Shelton JC, Bader DL, Lee DA (2003) Mechanical conditioning influences the metabolic response of cell-seeded constructs. Cells Tissues Organ 175(3):140–150
Nebelung S, Gavenis K, Rath B, Tingart M, Ladenburger A, Stoffel M, Zhou B, Mueller-Rath R (2011) Continuous cyclic compressive loading modulates biological and mechanical properties of collagen hydrogels seeded with human chondrocytes. Biorheology 48(5–6):247–261
Chen T, Buckley M, Cohen I, Bonassar L, Awad HA (2012) Insights into interstitial flow, shear stress, and mass transport effects on ECM heterogeneity in bioreactor-cultivated engineered cartilage hydrogels. Biomech Model Mechanobiol 11(5):689–702
Natenstedt J, Kok AC, Dankelman J, Tuijthof GJ (2015) What quantitative mechanical loading stimulates in vitro cultivation best? J Exp Orthop 2(1):15
Chen C, Tambe DT, Deng LH, Yang L (2013) Biomechanical properties and mechanobiology of the articular chondrocyte. Am J Physiol-Cell Physiol 305(12):C1202–C1208
Ling Wang HS, Nie Jichang, Li Dichen, Fan Hongbin, Jin Zhongmin, Liu Chaozong (2018) Functional testing on engineered cartilage to identify the role played by shearing. Med Eng Phys 51:17–23
Grandolfo M, D’Andrea P, Paoletti S, Martina M, Silvestrini G, Bonucci E, Vittur F (1993) Culture and differentiation of chondrocytes entrapped in alginate gels. Calcif Tissue Int 52(1):42–48
Fragonas E, Valente M, Pozzi-Mucelli M, Toffanin R, Rizzo R, Silvestri F, Vittur F (2000) Articular cartilage repair in rabbits by using suspensions of allogenic chondrocytes in alginate. Biomaterials 21(8):795–801. https://doi.org/10.1016/s0142-9612(99)00241-0
Wang S, An W, Yao Y, Chen R, Zheng X, Yang W, Zhao Y, Hu X, Jiang E, Bie YH, Chen ZQ, Ouyang P, Zhang H, Xiong H (2015) Interleukin 37 expression inhibits STAT3 to suppress the proliferation and invasion of human cervical cancer cells. J Cancer 6(10):962–969
Sittinger M, Lukanoff B, Burmester GR, Dautzenberg H (1996) Encapsulation of artificial tissues in polyelectrolyte complexes: preliminary studies. Biomaterials 17(10):1049–1051
Acknowledgements
The work was supported by National Key R&D Program of China [2018YFE0207900], Key R&D Program of Guangdong Province [2018B090906001], the Fundamental Research Funds for the Central Universities and the Youth Innovation Team of Shaanxi Universities and the EU via the H2020-MSCA-RISE-2016 program [734156].
Author information
Authors and Affiliations
Contributions
ZH participated in the study design, experimental research, data analysis, writing and editing of the manuscript. SW, AF and JK performed the experimental research and data analysis. JN performed the experimental research, the study design and data analysis. DL and CL performed writing and editing of the manuscript. LW performed the study design, writing and editing of the manuscript. All authors have read and approved the final manuscript and, therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
Corresponding author
Ethics declarations
Conflicts of interest
The authors declare that they have no conflict of interest.
Ethical approval
This research has been approved by the Animal Management Committee of Xi’an Jiaotong University.
Consent to participate
All authors agree to participate in the work related to this article.
Consent for publication
The manuscript was approved by all authors for publication.
Rights and permissions
About this article
Cite this article
Hao, Z., Wang, S., Nie, J. et al. Effects of bionic mechanical stimulation on the properties of engineered cartilage tissue. Bio-des. Manuf. 4, 33–43 (2021). https://doi.org/10.1007/s42242-020-00090-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s42242-020-00090-8