Human Knee Meniscus Regeneration Strategies: a Review on Recent Advances
- 36 Downloads
Purpose of Review
Lack of vascularity in the human knee meniscus often leads to surgical removal (total or partial meniscectomy) in the case of severe meniscal damage. However, complete recovery is in question after such removal as the meniscus plays an important role in knee stability. Thus, meniscus tissue regeneration strategies are of intense research interest in recent years.
The structural complexity and inhomogeneity of the meniscus have been addressed with processing technologies for precisely controlled three dimensional (3D) complex porous scaffold architectures, the use of biomolecules and nanomaterials.
The regeneration and replacement of the total meniscus have been studied by the orthopedic and scientific communities via successful pre-clinical trials towards mimicking the biomechanical properties of the human knee meniscus. Researchers have attempted different regeneration strategies which contribute to in vitro regeneration and are capable of repairing meniscal tears to some extent. This review discusses the present state of the art of these meniscus tissue engineering aspects.
KeywordsKnee meniscus Regeneration Tissue engineering Biomolecules Scaffolds Scaffold-free
The authors express deep gratitude to the management of PSG Institutions and Dr. P. Radhakrishnan, Director, PSG Institute of Advanced Studies, India, for their support to carry out this work.
Compliance with Ethical Standards
Conflict of Interest
Mamatha Pillai, J. Gopinathan, R. Selvakumar, and Amitava Bhattacharyya declare no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.Fairbank TJ. Knee joint changes after meniscectomy. Bone & Joint Journal. 1948;30(4):664–70.Google Scholar
- 5.Chambers MC, El-Amin SF. Tissue engineering of the meniscus: scaffolds for meniscus repair and replacement. Musculoskelet Regen 2015; 1.Google Scholar
- 12.Niu W, Guo W, Han S, Zhu Y, Liu S, Guo Q. Cell-based strategies for meniscus tissue engineering. Stem Cells Int. 2016;2016:1–10.Google Scholar
- 19.Zhang S, Matsushita T, Kuroda R, Nishida K, Matsuzaki T, Matsumoto T, et al. Local Administration of Simvastatin Stimulates Healing of an avascular meniscus in a rabbit model of a meniscal defect. Am J Sports Med. 2016;0363546516638342Google Scholar
- 20.•• Pillai MM, Elakkiya V, Gopinathan J, Sabarinath C, Shanthakumari S, Sahanand KS, et al. A combination of biomolecules enhances expression of E-cadherin and peroxisome proliferator-activated receptor gene leading to increased cell proliferation in primary human meniscal cells: an in vitro study. Cytotechnology. 2016;68(5):1747–61. This study highlights the development of an affordable biomocule combination for the enhancement for primary human knee meniscus cellular proliferation and ECM synthesis. CrossRefPubMedGoogle Scholar
- 21.•• Lee CH, Rodeo SA, Fortier LA, Lu C, Erisken C, Mao JJ. Protein-releasing polymeric scaffolds induce fibrochondrocytic differentiation of endogenous cells for knee meniscus regeneration in sheep. Sci Transl Med. 2014;6(266):266ra171. In this study, knee meniscus cartilage was regenerated with zonal matrix phenotype by using functionalized anatomically correct 3D-printed PCL scaffold in a sheep model. CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Van Der Bracht HA, Verdonk R, Verbruggen A, Elewaut D, Verdonk P. Cell-based meniscus tissue engineering. In: Ashammakhi N, Reis R, Chiellini E, editors. Topics in tissue engineering, vol 3, vol. 3. Oulu: Biomaterials and tissue engineering group; 2007. p. ch2_1–3.Google Scholar
- 24.Heidari M, Tahmasebi MN, Etemad S, Salehkhou S, Heidari-Vala H, Akhondi MM. In vitro human chondrocyte culture; a modified protocol. Middle-East J Sci Res. 2011;9(1):102–9.Google Scholar
- 32.Riedel K, Riedel F, Goessler UR, Holle G, Germann G, Sauerbier M. Current status of genetic modulation of growth factors in wound repair. Int J Mol Med. 2006;17:183e93.Google Scholar
- 34.Perrier-Groult E, Pasdeloup M, Malbouyres M, Galéra P, Mallein-Gerin F. Control of collagen production in mouse chondrocytes by using a combination of bone morphogenetic protein-2 and small interfering RNA targeting Col1a1 for hydrogel-based tissue-engineered cartilage. Tissue Eng Part C: Methods. 2013;19(8):652–64.CrossRefGoogle Scholar
- 45.•• Gopinathan J, Mano S, Elakkiya V, Pillai MM, Sahanand KS, Rai BD, et al. Biomolecule incorporated poly-ε-caprolactone nanofibrous scaffolds for enhanced human meniscal cell attachment and proliferation. RSC Adv. 2015;5(90):73552–61. This study demonstrates the mode of delivery of biomolecules for the regenerative purpose. It was confirmed that both through medium and scaffolds will be a better approach for the supplementation of biomolecules. CrossRefGoogle Scholar
- 46.Abbadessa A, Mouser VH, Blokzijl MM, Gawlitta D, Dhert WJ, Hennink WE, et al. A synthetic thermo-sensitive hydrogel for cartilage bioprinting and its biofunctionalization with polysaccharides. Biomacromolecules. 2016;17(6):2137–47.Google Scholar
- 47.Mi HY, Jing X, Salick MR, Cordie TM, Turng LS. Carbon nanotube (CNT) and nanofibrillated cellulose (NFC) reinforcement effect on thermoplastic polyurethane (TPU) scaffolds fabricated via phase separation using dimethyl sulfoxide (DMSO) as solvent. J Mech Behav Biomed Mater. 2016;62:417–27.CrossRefPubMedGoogle Scholar
- 53.Hua-ding LU, Dao-zhang CA, Kun W, De-hai SH, Gang W, Gui-e L. Whole meniscus regeneration using polymer scaffolds loaded with fibrochondrocytes. Chin J Traumatol. 2011;14(4):195–204.Google Scholar
- 61.Cengiz IF, Silva-Correia J, Pereira H, Espregueira-Mendes J, Oliveira JM, Reis RL. Advanced regenerative strategies for human knee meniscus. In Regenerative Strategies for the Treatment of Knee Joint Disabilities 2017; 271–285. Springer International PublishingGoogle Scholar
- 64.•• Mamatha PM, Elakkiya V, Gopinathan J, Amitava Bhattacharyya R, Selvakumar C. Sabarinath, K Santosh Sahanand , B.K Dinakar Rai, High density pellet culture for human knee meniscus tissue formation using a unique combination of medium. Regen Med. 2015;10–7s:S12–95. In this study, in a scaffold-free system, meniscus cartilage was regenerated by using affordable biomolecule combination. Google Scholar
- 67.• Pillai MM, Gopinathan J, Indumathi B, Manjoosha YR, Sahanand KS, Rai BD, et al. Silk–PVA Hybrid Nanofibrous Scaffolds for Enhanced Primary Human Meniscal Cell Proliferation. The Journal of membrane biology. 2016;249(6):813–22. In this study, Silk rich PVA scaffolds were fabricated to minimize the limitations of both the polymers for meniscus tissue engineering CrossRefPubMedGoogle Scholar
- 68.•• Gopinathan J, Pillai MM, Sahanand KS, Rai BD, Selvakumar R, Bhattacharyya A. Synergistic effect of electrical conductivity and biomolecules on human meniscal cell attachment, growth, and proliferation in poly-ε-caprolactone nanocomposite scaffolds. Biomedical Materials. 2017;12(6):065001. This study investigates the synergistic effect of nanofillers and biomolecule functionalization on to the PCL scaffolds on enhancement of cellular proliferation and ECM synthesis CrossRefPubMedGoogle Scholar
- 69.• Pillai MM, Elakkiya Venugopal, Lakshmipriya H, Janarthanan Gopinathan, Selvakumar Rajendran, Amitava Bhattacharyya. A novel method to develop three dimensional (3D) silk-PVA microenvironments for bone tissue engineering – an in vitro study. Biomedical Physics & Engineering Express. 2017. http://iopscience.iop.org/article/10.1088/2057-1976/aaa0af. In this study, a 3D porous scaffold was developed using Silk-PVA blend for tissue engineering applications.
- 71.Yang Y, Chen Z, Song X, Zhang Z, Zhang J, Shung KK, Zhou Q, Chen Y. Biomimetic Anisotropic Reinforcement Architectures by Electrically Assisted Nanocomposite 3D Printing. Advanced Materials. 2017;29(11).Google Scholar
- 74.Kanani AG, Bahrami SH. Review on electrospun nanofibers scaffold and biomedical applications. Trends Biomater Artif Organs. 2010;24(2):93–115.Google Scholar
- 78.Forriol F, Giuseppe Longo U, Duart J, Ripalda P, Vaquero J, Loppini M, et al. VEGF, BMP-7, MatrigelTM, hyaluronic acid, in vitro cultured chondrocytes and trephination for healing of the avascular portion of the meniscus. an experimental study in sheep. Current Stem Cell Research & Therapy. 2015;10(1):69–76.CrossRefGoogle Scholar
- 80.Kwak HS, Nam J, Lee JH, Kim HJ, Yoo JJ. Meniscal repair in vivo using human chondrocyte-seeded PLGA mesh scaffold pretreated with platelet-rich plasma. Journal of tissue engineering and regenerative medicine. 2017; 1;11(2):471-480Google Scholar
- 84.Qiao B, Padilla SR, Benya PD. Transforming growth factor (TGF)-β-activated kinase 1 mimics and mediates TGF-β-induced stimulation of type II collagen synthesis in chondrocytes independent of Col2a1 transcription and Smad3 signaling. Journal of Biological Chemistry. 2005;280(17):17562–71.CrossRefPubMedGoogle Scholar
- 88.Gropper SS, Smith LJ, Groff JL. Advanced nutrition and human metabolism. Wadsworth, USA: Cengage Learning; 2009.Google Scholar
- 89.Sriram D, Yogeeswari P. Medical chemistry. 2nd ed. New York: Dorling Kindersley; 2010.Google Scholar
- 90.Yoon JJ, Nam YS, Kim JH, Park TG. Surface immobilization of galactose onto aliphatic biodegradable polymers for hepatocyte culture. Biotechnology and bioengineering. 2002; 78(1):1-0.Google Scholar
- 96.Gleeson JP, O'Brien FJ. Composite scaffolds for orthopaedic regenerative medicine. INTECH Open Access Publisher; 2011.Google Scholar
- 98.• Pillai MM, Akshaya TR, Elakkiya V, Gopinathan J, Sahanand KS, Rai BD, et al. Egg shell membrane–a potential natural scaffold for human meniscal tissue engineering: an in vitro study. RSC Advances. 2015;5(93):76019–25. In this study process optimization of egg shell membrane was carried out and found that autoclaved eggshell membrane has the potential for meniscus tissue engineering CrossRefGoogle Scholar
- 100.Maiti S, Shrivastava NK, Suin S, Khatua BB. A strategy for achieving low percolation and high electrical conductivity in melt-blended polycarbonate (PC)/multiwall carbon nanotube (MWCNT) nanocomposites: Electrical and thermo-mechanical properties. Express Polymer Letters. 2013; 7(6).Google Scholar
- 104.Yuan X, Arkonac DE, Chao PH, Vunjak-Novakovic G. Electrical stimulation enhances cell migration and integrative repair in the meniscus. Scientific reports. 2014; 4.Google Scholar
- 107.Zhang C, Wang L, Zhai T, Wang X, Dan Y, Turng LS. The surface grafting of graphene oxide with poly (ethylene glycol) as a reinforcement for poly (lactic acid) nanocomposite scaffolds for potential tissue engineering applications. Journal of the Mechanical Behavior of Biomedical Materials. 2016;53:403–13.CrossRefPubMedGoogle Scholar