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A Comprehensive Review of Stem Cells for Cartilage Regeneration in Osteoarthritis

  • Gauthaman Kalamegam
  • Adnan Memic
  • Emma Budd
  • Mohammed Abbas
  • Ali Mobasheri
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1089)

Abstract

Osteoarthritis (OA) is an age related joint disease associated with degeneration and loss of articular cartilage. Consequently, OA patients suffer from chronic joint pain and disability. Weight bearing joints and joints that undergo repetitive stress and excessive ‘wear and tear’ are particularly prone to developing OA. Cartilage has a poor regenerative capacity and current pharmacological agents only provide symptomatic pain relief. OA patients that respond poorly to conventional therapies are ultimately treated with surgical procedures to promote cartilage repair by implantation of artificial joint structures (arthroplasty) or total joint replacement (TJR). In the last two decades, stem cells derived from various tissues with varying differentiation and tissue regeneration potential have been used for the treatment of OA either alone or in combination with natural or synthetic scaffolds to aid cartilage repair. Although stem cells can be differentiated into chondrocytes in vitro or aid cartilage regeneration in vivo, their potential for OA management remains limited as cartilage regenerated by stem cells fails to fully recapitulate the structural and biomechanical properties of the native tissue. Efficient tissue regeneration remains elusive despite the simple design of cartilage, which unlike most other tissues is avascular and aneural, consisting of a single cell type. In this article, we have comprehensively reviewed the types of stem cells that have been proposed or tested for the management of OA, their potential efficacy as well as their limitations. We also touch on the role of biomaterials in cartilage tissue engineering and examine the prospects for their use in cell-based therapies.

Keywords

Chondrocytes In vitro In vivo Osteoarthritis Regenerative medicine Stem cells 

Abbreviations

2D

Two dimensional

3D

Three dimensional

ACI

Autologous chondrocyte implantation

ACT

Autologous chondrocyte transplantation

BM

Bone marrow

BMAC

Bone marrow aspirate concentrate

BMP

Bone morphogenetic protein

CD

Cluster of Differentiation

COX-2

Cyclooxygenase-2

CP

Cartilage pellet

EBs

Embryoid bodies

ESCs

Embryonic stem cells

FDA

Food and drug administration

HA

Hyaluronic acid

HSCs

Haematopoietic stem cells

iPSCs

Induced pluripotent stem cells

ISCT

International Society for Cellular Therapy

MMP-13

Matrix metallo-proteinase-13

MSCs

Mesenchymal stem cells

NSAID

Nonsteroidal anti-inflammatory drug

OA

Osteoarthritis

PRP

Platelet rich plasma

SF

Synovial Fluid

SNRIs

Serotonin-norepinephrine reuptake inhibitors

TGF-β

Transforming growth factor beta

TKA

Total knee arthroplasty

Notes

Acknowledgements

The authors acknowledge the financial support provided by the “Sheikh Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis by Stem Cells” and the stem cell laboratory facility at CEGMR and King Abdulaziz University Hospital.

Conflicts of Interest

The authors declare no conflict of interests.

Competing Interests and Disclosures

The authors declare no competing interests.

Author’s Contributions

G. Kalamegam and A. Memic were involved in intellectual contribution and manuscript writing. MA and EB were involved in intellectual contribution and editing of the manuscript. A. Mobasheri contributed to the synthesis and editing of the manuscript.

References

  1. Abbas M (2017) Combination of bone marrow mesenchymal stem cells and cartilage fragments contribute to enhanced repair of osteochondral defects. Bioinformation 13:196CrossRefGoogle Scholar
  2. Al Faqeh H, Hamdan BMYN, Chen HC, Aminuddin BS, Ruszymah BHI (2012) The potential of intra-articular injection of chondrogenic-induced bone marrow stem cells to retard the progression of osteoarthritis in a sheep model. Exp Gerontol 47:458–464CrossRefGoogle Scholar
  3. Al-Arfaj A, Al-Boukai A (2002) Prevalence of radiographic knee osteoarthritis in Saudi Arabia. Clin Rheumatol 21:142–145CrossRefGoogle Scholar
  4. Aldahmash A et al (2013) Teratoma formation in immunocompetent mice after syngeneic and allogeneic implantation of germline capable mouse embryonic stem cells. Asian Pac J Cancer Prev 14:5705–5711CrossRefGoogle Scholar
  5. Apelgren P, Amoroso M, Lindahl A, Brantsing C, Rotter N, Gatenholm P, Kolby L (2017) Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo. PLoS One 12:e0189428.  https://doi.org/10.1371/journal.pone.0189428CrossRefPubMedPubMedCentralGoogle Scholar
  6. Armiento AR, Stoddart MJ, Alini M, Eglin D (2018) Biomaterials for articular cartilage tissue engineering: learning from biology. Acta Biomater 65:1–20.  https://doi.org/10.1016/j.actbio.2017.11.021CrossRefPubMedGoogle Scholar
  7. Arslan-Yildiz A, El Assal R, Chen P, Guven S, Inci F, Demirci U (2016) Towards artificial tissue models: past, present, and future of 3D bioprinting. Biofabrication 8:014103CrossRefGoogle Scholar
  8. Bertassoni LE et al (2014) Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs. Lab Chip 14:2202–2211.  https://doi.org/10.1039/c4lc00030gCrossRefPubMedPubMedCentralGoogle Scholar
  9. Bianco P, Robey PG (2015) Skeletal stem cells. Development 142:1023–1027CrossRefGoogle Scholar
  10. Bianco P, Robey PG, Simmons PJ (2008) Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell 2:313–319CrossRefGoogle Scholar
  11. Bongso A (2006) Blastocyst culture for deriving human embryonic stem cells. In: Human embryonic stem cell protocols. Springer, New York, pp 13–22CrossRefGoogle Scholar
  12. Brittberg M (2008) Autologous chondrocyte implantation—technique and long-term follow-up. Injury 39:40–49CrossRefGoogle Scholar
  13. Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331:889–895CrossRefGoogle Scholar
  14. Budd E, Waddell S, De Andres MC, Oreffo RO (2017) The potential of microRNAs for stem cell-based therapy for degenerative skeletal diseases. Curr Mol Biol Rep 3:263–275CrossRefGoogle Scholar
  15. Buschmann MD, Hoemann CD, Hurtig MB, Shive MS (2007) Cartilage repair with chitosan-glycerol phosphate-stabilized blood clots. In: Cartilage repair strategies. Humana Press, Totowa, pp 85–104CrossRefGoogle Scholar
  16. Calabrese G et al (2017) In vivo evaluation of biocompatibility and Chondrogenic potential of a cell-free collagen-based scaffold. Front Physiol 8:984.  https://doi.org/10.3389/fphys.2017.00984CrossRefPubMedPubMedCentralGoogle Scholar
  17. Chappell AS, Desaiah D, Liu-Seifert H, Zhang S, Skljarevski V, Belenkov Y, Brown JP (2011) A double-blind, randomized, placebo-controlled study of the efficacy and safety of duloxetine for the treatment of chronic pain due to osteoarthritis of the knee. Pain Pract 11:33–41CrossRefGoogle Scholar
  18. Christensen R, Astrup A, Bliddal H (2005) Weight loss: the treatment of choice for knee osteoarthritis? A randomized trial. Osteoarthr Cartil 13:20–27CrossRefGoogle Scholar
  19. Daly AC, Critchley SE, Rencsok EM, Kelly DJ (2016) A comparison of different bioinks for 3D bioprinting of fibrocartilage and hyaline cartilage. Biofabrication 8:045002.  https://doi.org/10.1088/1758-5090/8/4/045002CrossRefPubMedGoogle Scholar
  20. Das S et al (2015) Bioprintable, cell-laden silk fibroin-gelatin hydrogel supporting multilineage differentiation of stem cells for fabrication of three-dimensional tissue constructs. Acta Biomater 11:233–246.  https://doi.org/10.1016/j.actbio.2014.09.023CrossRefPubMedGoogle Scholar
  21. De Coppi P et al (2007) Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 25:100–106CrossRefGoogle Scholar
  22. DeLemos BP, Xiang J, Benson C, Gana TJ, Pascual MLG, Rosanna R, Fleming B (2011) Tramadol hydrochloride extended-release once-daily in the treatment of osteoarthritis of the knee and/or hip: a double-blind, randomized, dose-ranging trial. Am J Ther 18:216–226CrossRefGoogle Scholar
  23. Diekman BO, Rowland CR, Lennon DP, Caplan AI, Guilak F (2009) Chondrogenesis of adult stem cells from adipose tissue and bone marrow: induction by growth factors and cartilage-derived matrix. Tissue Eng A 16:523–533CrossRefGoogle Scholar
  24. Dominici M et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317CrossRefGoogle Scholar
  25. Duarte Campos DF, Drescher W, Rath B, Tingart M, Fischer H (2012) Supporting biomaterials for articular cartilage repair. Cartilage 3:205–221.  https://doi.org/10.1177/1947603512444722CrossRefPubMedPubMedCentralGoogle Scholar
  26. Duchi S et al (2017) Handheld co-axial bioprinting: application to in situ surgical cartilage repair. Sci Rep 7:5837.  https://doi.org/10.1038/s41598-017-05699-xCrossRefPubMedPubMedCentralGoogle Scholar
  27. Ernst E, Posadzki P (2011) Complementary and alternative medicine for rheumatoid arthritis and osteoarthritis: an overview of systematic reviews. Curr Pain Headache Rep 15:431–437CrossRefGoogle Scholar
  28. Filardo G et al (2012) Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskelet Disord 13:229.  https://doi.org/10.1186/1471-2474-13-229CrossRefPubMedPubMedCentralGoogle Scholar
  29. Fong C-Y, Subramanian A, Gauthaman K, Venugopal J, Biswas A, Ramakrishna S, Bongso A (2012) Human umbilical cord Wharton’s jelly stem cells undergo enhanced chondrogenic differentiation when grown on nanofibrous scaffolds and in a sequential two-stage culture medium environment. Stem Cell Rev Rep 8:195–209CrossRefGoogle Scholar
  30. Foyt DA, Norman MDA, Yu TTL, Gentleman E (2018) Exploiting advanced hydrogel technologies to address key challenges in regenerative medicine. Adv Healthc Mater.  https://doi.org/10.1002/adhm.201700939
  31. Gooding C, Bartlett W, Bentley G, Skinner J, Carrington R, Flanagan A (2006) A prospective, ranomised study comparing two techniques of autologous chondrocyte implantation for osteochondral defects in the knee: periosteum covered versus type I/III collagen covered. Knee 13:203–210CrossRefGoogle Scholar
  32. Grogan SP, Miyaki S, Asahara H, D D’Lima D, Lotz MK (2009) Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis. Arthritis Res Ther 11:R85CrossRefGoogle Scholar
  33. Guillot PV, Gotherstrom C, Chan J, Kurata H, Fisk NM (2007) Human first-trimester fetal MSC express pluripotency markers and grow faster and have longer telomeres than adult MSC. Stem Cells 25:646–654CrossRefGoogle Scholar
  34. Hasan A, Paul A, Memic A, Khademhosseini A (2015) A multilayered microfluidic blood vessel-like structure. Biomed Microdevices 17:88.  https://doi.org/10.1007/s10544-015-9993-2CrossRefPubMedPubMedCentralGoogle Scholar
  35. Huang W-N, Tso TK (2018) Etoricoxib improves osteoarthritis pain relief, joint function, and quality of life in the extreme elderly. Bosn J Basic Med Sci 18:87–94.Google Scholar
  36. Ismail AI, Al-Abdulwahab AH, Al-Mulhim AS (2006) Osteoarthritis of knees and obesity in Eastern Saudi Arabia. Saudi Med J 27:1742–1744PubMedGoogle Scholar
  37. Jang J, Yi H-G, Cho D-W (2016) 3D printed tissue models: present and future. ACS Biomate Sci Eng 2(10):1722–1731CrossRefGoogle Scholar
  38. Jiang YZ, Zhang SF, Qi YY, Wang LL, Ouyang HW (2011) Cell transplantation for articular cartilage defects: principles of past, present, and future practice. Cell Transplant 20:593–607CrossRefGoogle Scholar
  39. Kang HW, Lee SJ, Ko IK, Kengla C, Yoo JJ, Atala A (2016) A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat Biotechnol 34:312–319.  https://doi.org/10.1038/nbt.3413CrossRefPubMedGoogle Scholar
  40. Kern S, Eichler H, Stoeve J, Klüter H, Bieback K (2006) Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24:1294–1301CrossRefGoogle Scholar
  41. Lee PT, Li WJ (2017) Chondrogenesis of embryonic stem cell-derived mesenchymal stem cells induced by TGFβ1 and BMP7 through increased TGFβ receptor expression and endogenous TGFβ1 production. J Cell Biochem 118:172–181CrossRefGoogle Scholar
  42. Lee J-C et al (2012) Synovium-derived mesenchymal stem cells encapsulated in a novel injectable gel can repair osteochondral defects in a rabbit model. Tissue Eng A 18:2173–2186CrossRefGoogle Scholar
  43. Lee M et al (2017) A randomized, multicenter, phase III trial to evaluate the efficacy and safety of polmacoxib compared with celecoxib and placebo for patients with osteoarthritis clinics in orthopedic surgery 9:439–457Google Scholar
  44. Lotz M, Loeser RF (2012) Effects of aging on articular cartilage homeostasis. Bone 51:241–248CrossRefGoogle Scholar
  45. Mackay AM, Beck SC, Murphy JM, Barry FP, Chichester CO, Pittenger MF (1998) Chondrogenic differentiation of cultured human mesenchymal stem cells from marrow. Tissue Eng 4:415–428CrossRefGoogle Scholar
  46. Makris EA, Gomoll AH, Malizos KN, Hu JC, Athanasiou KA (2015) Repair and tissue engineering techniques for articular cartilage. Nat Rev Rheumatol 11:21–34.  https://doi.org/10.1038/nrrheum.2014.157CrossRefPubMedGoogle Scholar
  47. Manunta AF et al (2016) The use of embryonic cells in the treatment of osteochondral defects of the knee: an ovine in vivo study. Joints 4:70CrossRefGoogle Scholar
  48. Markstedt K, Mantas A, Tournier I, Martinez Avila H, Hagg D, Gatenholm P (2015) 3D bioprinting human chondrocytes with Nanocellulose-alginate bioink for cartilage tissue engineering applications. Biomacromolecules 16:1489–1496.  https://doi.org/10.1021/acs.biomac.5b00188CrossRefPubMedGoogle Scholar
  49. Mathis DT, Kaelin R, Rasch H, Arnold MP, Hirschmann MT (2017) Good clinical results but moderate osseointegration and defect filling of a cell-free multi-layered nano-composite scaffold for treatment of osteochondral lesions of the knee. Knee Surg Sports Traumatol Arthrosc 26(4):1273–1280.  https://doi.org/10.1007/s00167-017-4638-zCrossRefPubMedGoogle Scholar
  50. Mehrali M, Thakur A, Pennisi CP, Talebian S, Arpanaei A, Nikkhah M, Dolatshahi-Pirouz A (2016) Nanoreinforced hydrogels for tissue engineering: biomaterials that are compatible with load-bearing and electroactive tissues. Adv Mater 29(8):1603612CrossRefGoogle Scholar
  51. Memic A et al (2015) Hydrogels 2.0: improved properties with nanomaterial composites for biomedical applications. Biomed Mater 11:014104.  https://doi.org/10.1088/1748-6041/11/1/014104CrossRefPubMedGoogle Scholar
  52. Memic A et al (2017) Bioprinting technologies for disease modeling. Biotechnol Lett 39:1279–1290.  https://doi.org/10.1007/s10529-017-2360-zCrossRefPubMedGoogle Scholar
  53. Mistry H et al (2017) Autologous chondrocyte implantation in the knee: systematic review and economic evaluation. National Institute for Health Research, SouthamptonGoogle Scholar
  54. Mobasheri A, Rayman MP, Gualillo O, Sellam J, van der Kraan P, Fearon U (2017) The role of metabolism in the pathogenesis of osteoarthritis nature reviews rheumatology. Nat Rev Rheumatol 13(5):302–311CrossRefGoogle Scholar
  55. Mouser VHM et al (2017) Three-dimensional bioprinting and its potential in the field of articular cartilage regeneration. Cartilage 8:327–340.  https://doi.org/10.1177/1947603516665445CrossRefPubMedGoogle Scholar
  56. Murphy SV, Atala A (2014) 3D bioprinting of tissues and organs. Nat Biotechnol 32:773–785.  https://doi.org/10.1038/nbt.2958CrossRefPubMedGoogle Scholar
  57. Murphy C, Mobasheri A, Tancos Z, Kobolak J, Dinnyes A (2017) The Potency of induced pluripotent stem cells in cartilage regeneration and osteoarthritis treatment. In: Advances in experimental medicine and biology. Springer, Boston, pp 1–14.  https://doi.org/10.1007/5584_2017_141
  58. Musumeci G, Aiello FC, Szychlinska MA, Di Rosa M, Castrogiovanni P, Mobasheri A (2015) Osteoarthritis in the XXIst century: risk factors and behaviours that influence disease onset and progression. Int J Mol Sci 16:6093–6112CrossRefGoogle Scholar
  59. Nam Y, Rim YA, Jung SM, Ju JH (2017) Cord blood cell-derived iPSCs as a new candidate for chondrogenic differentiation and cartilage regeneration. Stem Cell Res Ther 8:16CrossRefGoogle Scholar
  60. Nguyen U-SD, Ayers DC, Li W, Harrold LR, Franklin PD (2016) Preoperative pain and function: profiles of patients selected for total knee arthroplasty. J Arthroplast 31:2402–2407, e2402CrossRefGoogle Scholar
  61. Niemeyer P et al (2014) Long-term outcomes after first-generation autologous chondrocyte implantation for cartilage defects of the knee. Am J Sports Med 42:150–157CrossRefGoogle Scholar
  62. Ober TJ, Foresti D, Lewis JA (2015) Active mixing of complex fluids at the microscale. Proc Natl Acad Sci U S A 112:12293–12298.  https://doi.org/10.1073/pnas.1509224112CrossRefPubMedPubMedCentralGoogle Scholar
  63. Ozbolat IT, Peng W, Ozbolat V (2016) Application areas of 3D bioprinting. Drug Discov Today 21:1257–1271.  https://doi.org/10.1016/j.drudis.2016.04.006CrossRefPubMedPubMedCentralGoogle Scholar
  64. Park JH, Jang J, Lee JS, Cho DW (2016) Current advances in three-dimensional tissue/organ printing. Tissue Eng Regen Med 13:612–621CrossRefGoogle Scholar
  65. Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A (2013) Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med 41:356–364.  https://doi.org/10.1177/0363546512471299CrossRefPubMedGoogle Scholar
  66. Patrascu JM, Freymann U, Kaps C, Poenaru DV (2010) Repair of a post-traumatic cartilage defect with a cell-free polymer-based cartilage implant: a follow-up at two years by MRI and histological review. J Bone Joint Surg (Br) 92:1160–1163.  https://doi.org/10.1302/0301-620X.92B8.24341CrossRefGoogle Scholar
  67. Patrascu JM et al (2013) Polyglycolic acid-hyaluronan scaffolds loaded with bone marrow-derived mesenchymal stem cells show chondrogenic differentiation in vitro and cartilage repair in the rabbit model. J Biomed Mater Res B Appl Biomater 101:1310–1320.  https://doi.org/10.1002/jbm.b.32944CrossRefPubMedGoogle Scholar
  68. Pera MF, Reubinoff B, Trounson A (2000) Human embryonic stem cells. J Cell Sci 113:5–10PubMedGoogle Scholar
  69. Poulet B, Staines KA (2016) New developments in osteoarthritis and cartilage biology. Curr Opin Pharmacol 28:8–13CrossRefGoogle Scholar
  70. Richardson SM et al (2016) Mesenchymal stem cells in regenerative medicine: focus on articular cartilage and intervertebral disc regeneration. Methods 99:69–80.  https://doi.org/10.1016/j.ymeth.2015.09.015CrossRefPubMedGoogle Scholar
  71. Richter W (2009) Mesenchymal stem cells and cartilage in situ regeneration. J Intern Med 266:390–405.  https://doi.org/10.1111/j.1365-2796.2009.02153.xCrossRefPubMedGoogle Scholar
  72. Saito T et al (2015) Hyaline cartilage formation and tumorigenesis of implanted tissues derived from human induced pluripotent stem cells. Biomed Res 36:179–186CrossRefGoogle Scholar
  73. Schon BS, Hooper GJ, Woodfield TB (2017) Modular tissue assembly strategies for biofabrication of engineered cartilage. Ann Biomed Eng 45:100–114.  https://doi.org/10.1007/s10439-016-1609-3CrossRefPubMedGoogle Scholar
  74. Shabestari M, Vik J, Reseland J, Eriksen E (2016) Bone marrow lesions in hip osteoarthritis are characterized by increased bone turnover and enhanced angiogenesis. Osteoarthr Cartil 24:1745–1752CrossRefGoogle Scholar
  75. Siclari A, Mascaro G, Gentili C, Cancedda R, Boux E (2012) A cell-free scaffold-based cartilage repair provides improved function hyaline-like repair at one year. Clin Orthop Relat Res 470:910–919.  https://doi.org/10.1007/s11999-011-2107-4CrossRefPubMedGoogle Scholar
  76. Stanish WD et al (2013) Novel scaffold-based BST-CarGel treatment results in superior cartilage repair compared with microfracture in a randomized controlled trial. J Bone Joint Surg Am 95:1640–1650.  https://doi.org/10.2106/JBJS.L.01345CrossRefPubMedGoogle Scholar
  77. Suchorska WM, Augustyniak E, Richter M, Łukjanow M, Filas V, Kaczmarczyk J, Trzeciak T (2017) Modified methods for efficiently differentiating human embryonic stem cells into chondrocyte-like cells. Adv Hyg Exp Med/Postepy Higieny i Medycyny Doswiadczalnej 71:500–509Google Scholar
  78. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676CrossRefGoogle Scholar
  79. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872CrossRefGoogle Scholar
  80. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147CrossRefGoogle Scholar
  81. Vaidya M (2015) Startups tout commercially 3D-printed tissue for drug screening. Nat Med 21:2–2CrossRefGoogle Scholar
  82. Watt FM, Huck WT (2013) Role of the extracellular matrix in regulating stem cell fate. Nat Rev Mol Cell Biol 14:467–473CrossRefGoogle Scholar
  83. Wise JK, Yarin AL, Megaridis CM, Cho M (2008) Chondrogenic differentiation of human mesenchymal stem cells on oriented nanofibrous scaffolds: engineering the superficial zone of articular cartilage. Tissue Eng A 15:913–921CrossRefGoogle Scholar
  84. Yang J, Zhang YS, Yue K, Khademhosseini A (2017) Cell-laden hydrogels for osteochondral and cartilage tissue engineering. Acta Biomater 57:1–25.  https://doi.org/10.1016/j.actbio.2017.01.036CrossRefPubMedPubMedCentralGoogle Scholar
  85. Zhang Y, Jordan JM (2010) Epidemiology of osteoarthritis. Clin Geriatr Med 26:355–369CrossRefGoogle Scholar
  86. Zhang W, Ouyang H, Dass CR, Xu J (2016) Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res 4:15040CrossRefGoogle Scholar
  87. Zhang YS et al (2017) 3D bioprinting for tissue and organ fabrication. Ann Biomed Eng 45:148–163.  https://doi.org/10.1007/s10439-016-1612-8CrossRefPubMedGoogle Scholar
  88. Zhu Z et al (2017) Cross-sectional and longitudinal associations between serum inflammatory cytokines and knee bone marrow lesions in patients with knee osteoarthritis. Osteoarthr Cartil 25:499–505CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Gauthaman Kalamegam
    • 1
    • 2
  • Adnan Memic
    • 3
  • Emma Budd
    • 4
  • Mohammed Abbas
    • 2
    • 5
  • Ali Mobasheri
    • 2
    • 4
    • 6
    • 7
  1. 1.Center of Excellence in Genomic Medicine ResearchKing Abdulaziz UniversityJeddahSaudi Arabia
  2. 2.Sheikh Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis with Stem CellsKing Abdulaziz UniversityJeddahSaudi Arabia
  3. 3.Center of NanotechnologyKing AbdulAziz UniversityJeddahSaudi Arabia
  4. 4.Department of Veterinary Pre-Clinical Sciences, School of Veterinary Medicine, Faculty of Health and Medical SciencesUniversity of SurreyGuildfordUK
  5. 5.Department of Orthopaedic Surgery, Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia
  6. 6.Arthritis Research UK Centre for Sport, Exercise and OsteoarthritisQueen’s Medical CentreNottinghamUK
  7. 7.Department of Regenerative MedicineState Research Institute Centre for Innovative MedicineVilniusLithuania

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