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Engineering    2017, Vol. 3 Issue (1) : 16 -27
Research |
Regenerative Engineering for Knee Osteoarthritis Treatment: Biomaterials and Cell-Based Technologies
Jorge L. Escobar Ivirico1,2,3,Maumita Bhattacharjee1,2,3,Emmanuel Kuyinu1,2,3,Lakshmi S. Nair1,2,3,4,5,Cato T. Laurencin1,2,3,4,5,6,7,8()
1. Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA
2. Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA
3. Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA
4. Department of Biomedical Engineering, School of Engineering, University of Connecticut, Storrs, CT 06269, USA
5. Department of Materials Science and Engineering, School of Engineering, University of Connecticut, Storrs, CT 06269, USA
6. Institute of Materials Science, University of Connecticut, Storrs, CT 06269, USA
7. Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA
8. Department of Chemical and Biomolecular Engineering, School of Engineering, University of Connecticut, Storrs, CT 06269, USA

Knee osteoarthritis (OA) is the most common form of arthritis worldwide. The incidence of this disease is rising and its treatment poses an economic burden. Two early targets of knee OA treatment include the predominant symptom of pain, and cartilage damage in the knee joint. Current treatments have been beneficial in treating the disease but none is as effective as total knee arthroplasty (TKA). However, while TKA is an end-stage solution of the disease, it is an invasive and expensive procedure. Therefore, innovative regenerative engineering strategies should be established as these could defer or annul the need for a TKA. Several biomaterial and cell-based therapies are currently in development and have shown early promise in both preclinical and clinical studies. The use of advanced biomaterials and stem cells independently or in conjunction to treat knee OA could potentially reduce pain and regenerate focal articular cartilage damage. In this review, we discuss the pathogenesis of pain and cartilage damage in knee OA and explore novel treatment options currently being studied, along with some of their limitations.

Keywords Knee osteoarthritis      Osteoarthritic pain      Mesenchymal stem cells      Biomaterials      Regenerative engineering     
Corresponding Authors: Cato T. Laurencin   
Just Accepted Date: 14 February 2017   Online First Date: 16 February 2017    Issue Date: 02 March 2017
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Jorge L. Escobar Ivirico
Maumita Bhattacharjee
Emmanuel Kuyinu
Lakshmi S. Nair
Cato T. Laurencin
Cite this article:   
Jorge L. Escobar Ivirico,Maumita Bhattacharjee,Emmanuel Kuyinu, et al. Regenerative Engineering for Knee Osteoarthritis Treatment: Biomaterials and Cell-Based Technologies[J]. Engineering, 2017, 3(1): 16 -27 .
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1   Kuyinu EL, Narayanan G, Nair LS, Laurencin CT. Animal models of osteoarthritis: classification, update, and measurement of outcomes. J Orthop Surg Res 2016; 11(1):1–27
doi: 10.1186/s13018-016-0346-5 pmid: 26837951
2   Glyn-Jones S, Palmer AJ, Agricola R, Price AJ, Vincent TL, Weinans H, et al. Osteoarthritis. Lancet 2015;386(9991):376–87
doi: 10.1016/S0140-6736(14)60802-3 pmid: 25748615
3   Neogi T. The epidemiology and impact of pain in osteoarthritis. Osteoarthritis Cartilage 2013;21(9):1145–53
doi: 10.1016/j.joca.2013.03.018 pmid: 23973124
4   Neogi T, Zhang Y. Epidemiology of osteoarthritis. Rheum Dis Clin North Am 2013;39(1):1–19
doi: 10.1016/j.rdc.2012.10.004
5   Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011?2012. JAMA 2014;311(8):806–4
doi: 10.1001/jama.2014.732 pmid: 24570244
6   Murphy L, Schwartz TA, Helmick CG, Renner JB, Tudor G, Koch G, et al. Lifetime risk of symptomatic knee osteoarthritis. Arthritis Rheum 2008;59(9):1207–13
doi: 10.1002/art.24021 pmid: 18759314
7   Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, et al. National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum 2008;58(1):26–35
doi: 10.1002/art.23176 pmid: 18163497
8   Hootman JM, Helmick CG. Projections of US prevalence of arthritis and associated activity limitations. Arthritis Rheum 2006;54(1):226–9
doi: 10.1002/art.21562 pmid: 16385518
9   Turkiewicz A, Petersson IF, Björk J, Hawker G, Dahlberg LE, Lohmander LS,et al. Current and future impact of osteoarthritis on health care: a population-based study with projections to year 2032. Osteoarthritis Cartilage 2014;22(11):1826–32
doi: 10.1016/j.joca.2014.07.015 pmid: 25084132
10   Le TK, Montejano LB, Cao Z, Zhao Y, Ang D. Healthcare costs associated with osteoarthritis in US patients. Pain Pract 2012;12(8):633–40
doi: 10.1111/j.1533-2500.2012.00535.x pmid: 22309128
11   Losina E, Paltiel AD, Weinstein AM, Yelin E, Hunter DJ, Chen SP, et al.Lifetime medical costs of knee osteoarthritis management in the United States: impact of extending indications for total knee arthroplasty. Arthritis CareRes (Hoboken) 2015;67 (2):203–15
doi: 10.1002/acr.22412 pmid: 25048053
12   Wilkie R, Hay EM, Croft P, Pransky G. Exploring how pain leads to productivity loss in primary care consulters for osteoarthritis: a prospective cohort study. PLoS One 2015;10 (4):e0120042
doi: 10.1371/journal.pone.0120042 pmid: 25849594
13   Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am 2007;89(4):780–5.17403800
doi: 10.2106/00004623-200704000-00012 pmid: 17403800.
14   Yoo JY, O’Malley MJ, Matsen Ko LJ, Cohen SB, Sharkey PF. Knee arthroplasty after subchondroplasty: early results, complications, and technical challenges. JArthroplasty 2016;31(10):2188–92
doi: 10.1016/j.arth.2015.12.051 pmid: 27430180
15   Cohen SB, Sharkey PF. Subchondroplasty for treating bone marrow lesions. JKnee Surg 2016;29(7):555–63
pmid: 26641077.
16   Laurencin CT, Khan Y. Regenerative engineering. Sci Trans Med 2012;4(160):160ed9
doi: 10.1126/scitranslmed.3004467 pmid: 23152324
17   Laurencin CT, Nair LS. The Quest toward limb regeneration: a regenerative engineering approach. Regen Biomater 2016;3(2):123–5
doi: 10.1093/rb/rbw002 pmid: 27047679
18   Arendt-minus;Nielsen L, Nie H, Laursen MB, Laursen BS, Madeleine P, Simonsen OH, et al. Sensitization in patients with painful knee osteoarthritis. Pain 2010;149(3):573–81
doi: 10.1016/j.pain.2010.04.003 pmid: 20418016
19   Connelly AE, Tucker AJ, Kott LS, Wright AJ, Duncan AM. Modifiable lifestyle factors are associated with lower pain levels in adults with knee osteoarthritis. Pain Res Manag 2015;20(5):241–8
doi: 10.1155/2015/389084
20   Miller RE, Miller RJ, Malfait AM. Osteoarthritis joint pain: the cytokine connection. Cytokine 2014;70(2):185–93
doi: 10.1016/j.cyto.2014.06.019 pmid: 25066335
21   Mease PJ, Hanna S, Frakes EP, Altman RD. Pain mechanisms in osteoarthritis: understanding the role of central pain and current approaches to its treatment. JRheumatol 2011;38(8):1546–51
doi: 10.3899/jrheum.100759 pmid: 21632678
22   McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-minus;Zeinstra SM, et al.OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage 2014;22 (3):363–88
doi: 10.1016/j.joca.2014.01.003 pmid: 24462672
23   Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, et al. American College of Rheumatology. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee .Arthritis Care Res (Hoboken) 2012;64(4):465–74
doi: 10.1002/acr.21596
24   Fransen M, McConnell S. Land-based exercise for osteoarthritis of the knee: a metaanalysis of randomized controlled trials. J Rheumatol 2009;36(6):1109–17
doi: 10.3899/jrheum.090058 pmid: 19447940
25   Fransen M, McConnell S, Harmer AR, Van der Esch M, Simic M, Bennell KL. Exercise for osteoarthritis of the knee. Cochrane DatabaseSyst Rev 2015;(1):CD004376
doi: 10.1002/14651858.cd004376.pub3
26   Silva LE, Valim V, Pessanha AP, Oliveira LM, Myamoto S, Jones A, et al. Hydrotherapy versus conventional land-based exercise for the management of patients with osteoarthritis of the knee: a randomized clinical trial. Phys Ther 2008;88(1):12–21
doi: 10.2522/ptj.20060040 pmid: 17986497
27   Batterham SI, Heywood S, Keating JL. Systematic review and meta-analysis comparing land and aquatic exercise for people with hip or knee arthritis on function, mobility and other health outcomes. BMC Musculoskelet Disord 2011;12:123
doi: 10.1186/1471-2474-12-123 pmid: 21635746
28   Barker AL, Talevski J, Morello RT, Brand CA, Rahmann AE, Urquhart DM. Effectiveness of aquatic exercise for musculoskeletal conditions: a meta-minus;analysis. Arch Phys Med Rehabil 2014;95(9):1776–86
doi: 10.1016/j.apmr.2014.04.005 pmid: 24769068
29   Ye J, Cai S, Zhong W, Cai S, Zheng Q. Effects of tai chi for patients with knee osteoarthritis: a systematic review. JPhysTherSci 2014;26(7):1133–7
doi: 10.1589/jpts.26.1133 pmid: 25140112
30   Kolasinski SL, Garfinkel M, Tsai AG, Matz W, Van Dyke A, Schumacher HR. Iyengar yoga for treating symptoms of osteoarthritis of the knees: a pilot study. J Altern Complement Med 2005;11(4):689–93
doi: 10.1089/acm.2005.11.689 pmid: 16131293
31   van Laar M, Pergolizzi JVJr, Mellinghoff HU, Merchante IM, Nalamachu S, O’Brien J, et al. Pain treatment in arthritis-related pain: beyond NSAIDs. Open Rheumatolo J 2012;6:320–30
doi: 10.2174/1874312901206010320 pmid: 23264838
32   Lapane KL, Yang S, Driban JB, Liu SH, Dubé CE, McAlindon TE, et al. Effects of prescription nonsteroidal antiinflammatory drugs on symptoms and disease progression among patients with knee osteoarthritis. Arthritis Rheumatol 2015;67(3):724–32
doi: 10.1002/art.38933 pmid: 25369996
33   Derry S, Moore RA, Rabbie R. Topical NSAIDs for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev 2012;(9):CD007400.
34   Pergolizzi J, Böger RH, Budd K, Dahan A, Erdine S, Hans G, et al. Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone). Pain Pract 2008;8(4):287–313
doi: 10.1111/j.1533-2500.2008.00204.x pmid: 18503626
35   Inacio MC, Pratt NL, Roughead EE, Paxton EW, Graves SE. Opioid use after total hip arthroplasty surgery is associated with revision surgery. BMC Musculoskelet Disord 2016;17:122
doi: 10.1186/s12891-016-0970-6 pmid: 26965992
36   Khanna IK, Pillarisetti S. Buprenorphine—an attractive opioid with underutilized potential in treatment of chronic pain. JPain Res 2015:8:859–70
pmid: 26672499.
37   Ramiro S, Radner H, van der Heijde D, van Tubergen A, Buchbinder R, Aletaha D,et al. Combination therapy for pain management in inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis). Cochrane DatabaseSyst Rev 2011;(10):CD008886
doi: 10.1002/14651858.cd008886.pub2
38   Altman R, Hochberg M, Gibofsky A, Jaros M, Young C. Efficacy and safety of low-dose SoluMatrix meloxicam in the treatment of osteoarthritis pain: a 12-week, phase 3 study. Curr Med Res Opin 2015;31(12):2331–43
doi: 10.1185/03007995.2015.1112772 pmid: 26503347
39   Wade WE, Spruill WJ. Tapentadol hydrochloride: a centrally acting oral analgesic. Clin Ther 2009;31(12):2804–18
doi: 10.1016/j.clinthera.2009.12.003 pmid: 20110020
40   McCarberg B. Tramadol extended-minus;release in the management of chronic pain. Ther Clin Risk Manag 2007;3(3):401–10
pmid: 18488071.
41   Rannou F, Pelletier JP, Martel-Pelletier J. Efficacy and safety of topical NSAIDs in the management of osteoarthritis: evidence from real-life setting trials and surveys. Semin Arthritis and Rheum 2016;45(4 Suppl):S18–21
doi: 10.1016/j.semarthrit.2015.11.007 pmid: 26806189
42   Zhang W, Nuki G, Moskowitz RW, Abramson S, Altman RD, Arden NK, et al. OARSI recommendations for the management of hip and knee osteoarthritis: part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage 2010;18(4):476–99
doi: 10.1016/j.joca.2010.01.013 pmid: 20170770
43   Wang ZY, Shi SY, Li SJ, Chen F, Chen H, Lin HZ, et al. Efficacy and safety of duloxetine on osteoarthritis knee pain: a meta-analysis of randomized controlled trials. Pain Med 2015;16(7):1373–85
doi: 10.1111/pme.12800 pmid: 26176791
44   Wadsworth LT, Kent JD, Holt RJ. Efficacy and safety of diclofenac sodium 2% topical solution for osteoarthritis of the knee: a randomized, double-blind, vehicle-controlled, 4 week study. Curr Med Res Opin 2016;32(2):241–50
doi: 10.1185/03007995.2015.1113400 pmid: 26506138
45   Biondi DM, Xiang J, Etropolski M, Moskovitz B. Tolerability and efficacy of tapentadol extended release in elderly patients≥75 years of age with chronic osteoarthritis knee or low back pain. J Opioid Manag 2015;11(5):393–403
doi: 10.5055/jom.2015.0289
46   Balazs EA, Denlinger JL. Viscosupplementation: a new concept in the treatment of osteoarthritis. J Rheumatol Suppl 1993;39:3–9
pmid: 8410881.
47   Altman RD, Åkermark C, Beaulieu AD, Schnitzer T;Durolane International Study Group. Efficacy and safety of a single intra-articular injection of non-animal stabilized hyaluronic acid (NASHA) in patients with osteoarthritis of the knee. Osteoarthritis Cartilage 2004;12(8):642–9
doi: 10.1016/j.joca.2004.04.010 pmid: 15262244
48   Fraser JR, Clarris BJ, Baxter E. Patterns of induced variation in the morphology, hyaluronic acid secretion, and lysosomal enzyme activity of cultured human synovial cells. Ann Rheum Dis 1979;38(3):287–94
doi: 10.1136/ard.38.3.287 pmid: 384932
49   Benke M, Shaffer B. Viscosupplementation treatment of arthritis pain. Curr Pain and Headache Rep 2009;13(6):440–6. 19889285
doi: 10.1007/s11916-009-0072-3 pmid: 19889285.
50   Supartz FX [package insert]. Tokyo: Seikagaku Corporation.2015 Apr.
51   Hyalgan [package insert]. Padua: Fidia Farmaceutici s.p.a.2014 May.
52   Euflexxa [package insert]. Parsippany: Ferring Pharmaceuticals, Inc. 2014 Sep.
53   Synvisc [package insert]. Ridgefield: Genzyme Biosurgery.2014Sep.
54   Synvisc-One [package insert]. Ridgefield: Genzyme Biosurgery.2014Sep.
55   Orthovisc [package insert]. Woburn: Anika Therapeutics, Inc.2006Feb.
56   Gel-One [package insert]. Tokyo: Seikagaku Corporation.2011May.
57   Monovisc [package insert]. Bedford: Anika Therapeutics, Inc.2014Feb.
58   Trigkilidas D, Anand A. The effectiveness of hyaluronic acid intra-articular injections in managing osteoarthritic knee pain. Ann R Coll Surg Engl 2013;95(8):545–51
doi: 10.1308/rcsann.2013.95.8.545 pmid: 24165334
59   Leopold SS, Redd BB, Warme WJ, Wehrle PA, Pettis PD, Shott S. Corticosteroid compared with hyaluronic acid injections for the treatment of osteoarthritis of the knee. a prospective, randomized trial. J Bone Joint Surg Am 2003;85–A(7):1197–203
doi: 10.2106/00004623-200307000-00003 pmid: 12851342
60   Kirchner M, Marshall D. A double-blind randomized controlled trial comparing alternate forms of high molecular weight hyaluronan for the treatment of osteoarthritis of the knee. Osteoarthritis Cartilage 2006;14(2):154–62
doi: 10.1016/j.joca.2005.09.003 pmid: 16242361
61   Petrella RJ, Petrella M. A prospective, randomized, double-blind, placebo controlled study to evaluate the efficacy of intraarticular hyaluronic acid for osteoarthritis of the knee. J Rheumatol 2006;33(5):951–6
pmid: 16652426.
62   Baker K, Grainger A, Niu J, Clancy, M, Guermazi A, Crema M, et al. Relation of synovitis to knee pain using contrast-enhanced MRIs. Ann Rheum Dis 2010;69(10):1779–83
doi: 10.1136/ard.2009.121426 pmid: 20472593
63   Saarakkala S, Julkunen P, Kiviranta P, Mäkitalo J, Jurvelin JS, Korhonen RK. Depth-wise progression of osteoarthritis in human articular cartilage: investigation of composition, structure and biomechanics. Osteoarthritis Cartilage 2010;18(1):73–81
doi: 10.1016/j.joca.2009.08.003 pmid: 19733642
64   Mort JS, Geng Y, Fisher WD, Roughley PJ. Aggrecan heterogeneity in articular cartilage from patients with osteoarthritis. BMC Musculoskelet Disord 2016;17:89
doi: 10.1186/s12891-016-0944-8 pmid: 26891838
65   Roughley PJ, Mort JS. The role of aggrecan in normal and osteoarthritic cartilage. JExp Orthop 2014;1(1):8
doi: 10.1186/s40634-014-0008-7 pmid: 26914753
66   Lahm A, Mrosek E, Spank H, Erggelet C, Kasch R, Esser J, et al. Changes in content and synthesis of collagen types and proteoglycans in osteoarthritis of the knee joint and comparison of quantitative analysis with Photoshop-based image analysis. ArchOrthopTrauma Surg 2010;130(4):557–64
doi: 10.1007/s00402-009-0981-y pmid: 19838720
67   Gelse K, Pöschl E, Aigner T. Collagens—structure, function, and biosynthesis. Adv Drug Deliv Rev 2003;55(12):1531–46
doi: 10.1016/j.addr.2003.08.002 pmid: 14623400
68   Troeberg L, Nagase H. Proteases involved in cartilage matrix degradation in osteoarthritis. BBA–Proteins and Proteomics 2012;1824(1):133–45
doi: 10.1016/j.bbapap.2011.06.020
69   Verma P, Dalal K. ADAMTS-4 and ADAMTS-5: key enzymes in osteoarthritis. J Cell Biochem 2011;112(12):3507–14
doi: 10.1002/jcb.23298 pmid: 21815191
70   Grenier S, Bhargava MM, Torzilli PA. An in vitro model for the pathological degradation of articular cartilage in osteoarthritis. J Biomech 2014;47(3):645–52
doi: 10.1016/j.jbiomech.2013.11.050 pmid: 24360770
71   Maldonado M, Nam J. The role of changes in extracellular matrix of cartilage in the presence of inflammation on the pathology of osteoarthritis. Biomed Res Int 2013;2013:284873
doi: 10.1155/2013/284873
72   Hoff P, Buttgereit F, Burmester GR, Jakstadt M, Gaber T, Andreas K, et al. Osteoarthritis synovial fluid activates pro-inflammatory cytokines in primary human chondrocytes. Int Orthop 2013;37(1):145–51
doi: 10.1007/s00264-012-1724-1 pmid: 23212731
73   Browne JE, Branch TP. Surgical alternatives for treatment of articular cartilage lesions. J AmAcad Orthop Surg 2000;8(3):180–9
doi: 10.5435/00124635-200005000-00005 pmid: 10874225
74   Ossendorf C, Steinwachs MR, Kreuz PC, Osterhoff G, Lahm A, Ducommun PP, et al. Autologous chondrocyte implantation (ACI) for the treatment of large and complex cartilage lesions of the knee. BMC Sports Sci Med Rehabil 2011;3(1):11
doi: 10.1186/1758-2555-3-11 pmid: 21599992
75   Oussedik S, Tsitskaris K, Parker D. Treatment of articular cartilage lesions of the knee by microfracture or autologous chondrocyte implantation: a systematic review. Arthroscopy 2015;31(4):732–44
doi: 10.1016/j.arthro.2014.11.023 pmid: 25660008
76   Steinwachs M, Kreuz PC. Autologous chondrocyte implantation in chondral defects of the knee with a type I/III collagen membrane: a prospective study with a 3-year follow-up. Arthroscopy 2007;23(4):381–7
doi: 10.1016/j.arthro.2006.12.003 pmid: 17418330
77   Kon E, Filardo G, Gobbi A, Berruto M, Andriolo L, Ferrua P, et al. Long-term results after hyaluronan-based MACT for the treatment of cartilage lesions of the patellofemoral joint. Am J Sports Med 2016;44(3):602–8
doi: 10.1177/0363546515620194 pmid: 26755690
78   Dean CS, Chahla J, Serra Cruz R, LaPrade RF. Fresh osteochondral allograft transplantation for treatment of articular cartilage defects of the knee. Arthrosc Tech 2016;5(1):e157–61
doi: 10.1016/j.eats.2015.10.015 pmid: 27274447
79   Migliaresi C, Motta A, DiBenedetto AT. Injectable scaffolds for bone and cartilage regeneration. In: Bronner F, Farach-Carson MC, Mikos AG, editors Engineering of functional skeletal tissues. London: Springer; 2007. p. 95–109
doi: 10.1007/978-1-84628-366-6_7
80   Minas T, Gomoll AH, Solhpour S, Rosenberger R, Probst C, Bryant T. Autologous chondrocyte implantation for joint preservation in patients with early osteoarthritis. Clin Orthop Relat Res 2010;468(1):147–57
doi: 10.1007/s11999-009-0998-0 pmid: 19653049
81   Estes BT, Wu AW, Guilak F. Potent induction of chondrocytic differentiation of human adipose-derived adult stem cells by bone morphogenetic protein 6. Arthritis Rheum 2006;54(4):1222–32
doi: 10.1002/art.21779 pmid: 16572454
82   Lee JC, Lee SY, Min HJ, Han SA, Jang J, Lee S, et al. Synovium-derived mesenchymal stem cells encapsulated in a novel injectable gel can repair osteochondral defects in a rabbit model. Tissue Eng Part A 2012;18(19–20):2173–86
doi: 10.1089/ten.tea.2011.0643 pmid: 22765885
83   Leijten JC, Georgi N, Wu L, van Blitterswijk CA, Karperien M. Cell sources for articular cartilage repair strategies: shifting from monocultures to cocultures. Tissue Eng Part B Rev 2013;19(1):31–40
doi: 10.1089/ten.teb.2012.0273 pmid: 22845048
84   Zhao W, Jin X, Cong Y, Liu Y, Fu J. Degradable natural polymer hydrogels for articular cartilage tissue engineering. J Chem Technol Biot 2013;88(3):327–39
doi: 10.1002/jctb.3970
85   Sun J, Zhao X, Illeperuma WR, Chaudhuri O, Oh KH, Mooney DJ, et al. Highly stretchable and tough hydrogels. Nature 2012;489(7414):133–6
doi: 10.1038/nature11409 pmid: 22955625
86   Amini AA, Nair LS. Injectable hydrogels for bone and cartilage repair. Biomed Mater 2012;7(2):024105
doi: 10.1088/1748-6041/7/2/024105 pmid: 22456837
87   Chung C, Burdick JA. Influence of three-dimensional hyaluronic acid microenvironments on mesenchymal stem cell chondrogenesis. Tissue Eng Part A 2009;15(2):243–54
doi: 10.1089/ten.tea.2008.0067 pmid: 19193129
88   Roberts JJ, Nicodemus GD, Giunta S, Bryant SJ. Incorporation of biomimetic matrix molecules in PEG hydrogels enhances matrix deposition and reduces load-induced loss of chondrocyte-secreted matrix. J Biomed Mater Res A 2011;97(3):281–91
doi: 10.1002/jbm.a.33057 pmid: 21442729
89   Bhattacharjee M, Coburn J, Centola M, Murab S, Barbero A, Kaplan DL, et al. Tissue engineering strategies to study cartilage development, degeneration and regeneration. Adv Drug Deliv Rev 2015;84:107–22
doi: 10.1016/j.addr.2014.08.010 pmid: 25174307
90   Lam J, Clark EC, Fong EL, Lee EJ, Lu S, Tabata Y, et al. Evaluation of cell-minus;laden polyelectrolyte hydrogels incorporating poly(L-lysine) for applications in cartilage tissue engineering. Biomaterials 2016;83:332–46
doi: 10.1016/j.biomaterials.2016.01.020 pmid: 26799859
91   Re’em T, Tsur-minus;Gang O, Cohen S. The effect of immobilized RGD peptide in macroporous alginate scaffolds on TGFβ1-induced chondrogenesis of human mesenchymal stem cells. Biomaterials 2010;31(26):6746–55
doi: 10.1016/j.biomaterials.2010.05.025 pmid: 20542332
92   Zhang L, Yuan T, Guo L, Zhang X. An in vitro study of collagen hydrogel to induce the chondrogenic differentiation of mesenchymal stem cells. J Biomed Mater Res A 2012;100(10):2717–25
doi: 10.1002/jbm.a.34194 pmid: 22623365
93   Strehin I, Nahas Z, Arora K, Nguyen T, Elisseeff J. A versatile pH sensitive chondroitin sulfate-PEG tissue adhesive and hydrogel. Biomaterials 2010;31(10):2788–97
doi: 10.1016/j.biomaterials.2009.12.033 pmid: 20047758
94   Bulpitt P, Aeschlimann D. New strategy for chemical modification of hyaluronic acid: preparation of functionalized derivatives and their use in the formation of novel biocompatible hydrogels. J BiomedMater Res 1999;47(2):152–69
doi: 10.1002/(SICI)1097-4636(199911)47:2<152::AID-JBM5>3.0.CO;2-I pmid: 10449626
95   Collins MN, Birkinshaw C. Hyaluronic acid based scaffolds for tissue engineering−a review. Carbohydr Polym 2013;92(2):1262–79
doi: 10.1016/j.carbpol.2012.10.028 pmid: 23399155
96   Domingues RM, Silva M, Gershovich P, Betta S, Babo P, Caridade SG, et al. Development of injectable hyaluronic acid/cellulose nanocrystals bionanocomposite hydrogels for tissue engineering applications. Bioconjug Chem 2015;26(8):1571–81
doi: 10.1021/acs.bioconjchem.5b00209 pmid: 26106949
97   Su W, Chen Y, Lin F. Injectable oxidized hyaluronic acid/adipic acid dihydrazide hydrogel for nucleus pulposus regeneration. Acta Biomater 2010;6(8):3044–55
doi: 10.1016/j.actbio.2010.02.037 pmid: 20193782
98   Wu A, Senter PD. Arming antibodies: prospects and challenges for immunoconjugates. Nat Biotechnol 2005;23(9):1137–46
doi: 10.1038/nbt1141 pmid: 16151407
99   Oommen OP, Wang S, Kisiel M, Sloff M, Hilborn J, Varghese OP. Smart design of stable extracellular matrix mimetic hydrogel: synthesis, characterization, and in vitro and in vivo evaluation for tissue engineering. Adv Funct Mater 2013;23(10):1273–80
doi: 10.1002/adfm.201201698
100   Wang S, Oommen OP, Yan H, Varghese OP. Mild and efficient strategy for site-selective aldehyde modification of glycosaminoglycans: tailoring hydrogels with tunable release of growth factor. Biomacromolecules 2013;14(7):2427–32
doi: 10.1021/bm400612h. pmid: 23721079
101   Zheng-Shu X, Liu Y, Palumbo FS, Luo Y, Prestwich GD. In situ crosslinkable hyaluronan hydrogels for tissue engineering. Biomaterials 2004;25(7-8):1339–48
doi: 10.1016/j.biomaterials.2003.08.014 pmid: 14643608
102   Burdick JA, Prestwich GD. Hyaluronic acid hydrogels for biomedical applications. Adv Mater 2011;23(12):H41–56
doi: 10.1002/adma.201003963 pmid: 21394792
103   Jin R, Moreira Teixeira LS, Krouwels A, Dijkstra PJ, van Blitterswijk CA, Karperien M, et al. Synthesis and characterization of hyaluronic acid-poly(ethylene glycol) hydrogels via Michael addition: an injectable biomaterial for cartilage repair. Acta Biomater 2010;6(6):1968–77
doi: 10.1016/j.actbio.2009.12.024 pmid: 20025999
104   Leach BJ, Bivens KA, Patrick CWJr, Schmidt CE. Photocrosslinked hyaluronic acid hydrogels: natural, biodegradable tissue engineering scaffolds. BiotechnolBioeng 2003;82(5):578–89
doi: 10.1002/bit.10605 pmid: 12652481
105   Yang X, Bakaic E, Hoare T, Cranston ED. Injectable polysaccharide hydrogels reinforced with cellulose nanocrystals: morphology, rheology, degradation, and cytotoxicity. Biomacromolecules 2013;14(12):4447–55
doi: 10.1021/bm401364z pmid: 24206059
106   Moutos FT, Guilak F. Functional properties of cell-minus;seeded three-dimensionally woven poly(ϵ-minus;caprolactone) scaffolds for cartilage tissue engineering. Tissue Eng Part A 2010;16(4):1291–301
doi: 10.1089/ten.tea.2009.0480 pmid: 19903085
107   Nguyen LH, Kudva AK, Saxena NS, Roy K. Engineering articular cartilage with spatially-varying matrix composition and mechanical properties from a single stem cell population using a multi-layered hydrogel. Biomaterials 2011;32(29):6946–52
doi: 10.1016/j.biomaterials.2011.06.014 pmid: 21723599
108   Song J, Kim R, Lee C, Tripathy N, Yoon KH, Lee G, et al. Effects of purified alginate sponge on the regeneration of chondrocytes: in vitro and in vivo. J Biomater Sci Polym E 2015;26(3):181–95
doi: 10.1080/09205063.2014.987570
109   Wang C, Yang K, Lin K, Liu Y, Liu H, Lin F. Cartilage regeneration in SCID mice using a highly organized three-dimensional alginate scaffold. Biomaterials 2012;33(1):120–7
doi: 10.1016/j.biomaterials.2011.09.042 pmid: 21982587
110   Zhang Q, Lu H, Kawazoe N, Chen G. Pore size effect of collagen scaffolds on cartilage regeneration. Acta Biomater 2014;10(5):2005–13
doi: 10.1016/j.actbio.2013.12.042 pmid: 24384122
111   Nanda HS, Chen S, Zhang Q, Kawazoe N, Chen G. Collagen scaffolds with controlled insulin release and controlled pore structure for cartilage tissue engineering. BioMed Res Int 2014;2014(24):623805
doi: 10.1155/2014/623805
112   Xu C, Lu W, Bian S, Liang J, Fan Y, Zhang X. Porous collagen scaffold reinforced with surfaced activated PLLA nanoparticles. Sci World J 2012;2012:695137
doi: 10.1100/2012/695137
113   Foss C, Merzari E, Migliaresi C, Motta A. Silk fibroin/hyaluronic acid 3D matrices for cartilage tissue engineering. Biomacromolecules 2013;14(1):38–47
doi: 10.1021/bm301174x pmid: 23134349
114   Ko CL, Tien YC, Wang J, Chen W. Characterization of controlled highly porous hyaluronan/gelatin cross-linking sponges for tissue engineering. J Mech Behav Biomed Mater 2012;14:227–38
doi: 10.1016/j.jmbbm.2012.06.019 pmid: 23122717
115   Schwartz Z, Griffon DJ, Fredericks LP, Lee HB, Weng HY. Hyaluronic acid and chondrogenesis of murine bone marrow mesenchymal stem cells in chitosan sponges. Am J Vet Res 2011;72(1):42–50
doi: 10.2460/ajvr.72.1.42 pmid: 21194334
116   Dinescu S, Galateanu B, Radu E, Hermenean A, Lungu A, Stancu IC,et al. A 3D porous gelatin-alginate-minus;based-minus;IPN acts as an efficient promoter of chondrogenesis from human adipose-derived stem cells. Stem Cells Int 2015;2015:252909.
117   Zhu Y, Wan Y, Zhang J, Yin D, Cheng W. Manufacture of layered collagen/chitosan-polycaprolactone scaffolds with biomimetic microarchitecture. Colloids Surf B Biointerfaces 2014;113:352–60
doi: 10.1016/j.colsurfb.2013.09.028 pmid: 24121078
118   Silva JM, Georgi N, Costa R, Sher P, Reis RL, Van Blitterswijk CA, et al. Nanostructured 3D constructs based on chitosan and chondroitin sulphate multilayers for cartilage tissue engineering. PLoS One 2013;8(2):e55451
doi: 10.1371/journal.pone.0055451 pmid: 23437056
119   Steele JA, McCullen SD, Callanan A, Autefage H, Accardi MA, Dini D, et al. Combinatorial scaffold morphologies for zonal articular cartilage engineering. Acta Biomater 2014;10(5):2065–75
doi: 10.1016/j.actbio.2013.12.030 pmid: 24370641
120   Moutos FT, Estes BT, Guilak F. Multifunctional hybrid three-dimensionally woven scaffolds for cartilage tissue engineering. Macromol Biosci 2010;10(11):1355–64
doi: 10.1002/mabi.201000124 pmid: 20857388
121   Garrigues NW, Little D, Sanchez-minus;Adams J, Ruch DS, Guilak F. Electrospun cartilage-derived matrix scaffolds for cartilage tissue engineering. J Biomed Mater Res A 2014;102(11):3998–4008
doi: 10.1002/jbm.a.35068 pmid: 24375991
122   Levorson EJ, Raman Sreerekha P, Chennazhi KP, Kasper FK, Nair SV, Mikos AG. Fabrication and characterization of multiscale electrospun scaffolds for cartilage regeneration. Biomed Mater 2013;8(1):014103
doi: 10.1088/1748-6041/8/1/014103 pmid: 23353096
123   Li W, Tuli R, Huang X, Laquerriere P, Tuan R. Multilineage differentiation of human mesenchymal stem cells in a three-dimensional nanofibrous scaffold. Biomaterials 2005;26(25):5158–66
doi: 10.1016/j.biomaterials.2005.01.002 pmid: 15792543
124   McCullen SD, Autefage H, Callanan A, Gentleman E, Stevens MM. Anisotropic fibrous scaffolds for articular cartilage regeneration. Tissue Eng Part A 2012;18(19–20):2073–83
doi: 10.1089/ten.tea.2011.0606 pmid: 22655795
125   Camarero-Espinosa S, Rothen–Rutishauser B, Foster EJ, Weder C. Articular cartilage: from formation to tissue engineering. Biomater Sci 2016;4(5):734–67
doi: 10.1039/C6BM00068A pmid: 26923076
126   Torricelli P, Gioffrè M, Fiorani A, Panzavolta S, Gualandi C, Fini M, et al. Co-electrospun gelatin–poly(L-minus;lactic acid) scaffolds: modulation of mechanical properties and chondrocyte response as a function of composition. Mater Sci Eng C Mater Biol Appl 2014;36:130–8
doi: 10.1016/j.msec.2013.11.050 pmid: 24433895
127   Younesi M, Islam A, Kishore V, Panit S, Akkus O. Fabrication of compositionally and topographically complex robust tissue forms by 3D-electrochemical compaction of collagen. Biofabrication 2015;7(3):035001
doi: 10.1088/1758-5090/7/3/035001 pmid: 26069162
128   Gupta PK, Das AK, Chullikana A, Majumdar AS . Mesenchymal stem cells for cartilage repair in osteoarthritis. Stem Cell Res Ther 2012;3(4):25
doi: 10.1186/scrt116 pmid: 22776206
129   Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006;98(5):1076–84
doi: 10.1002/jcb.20886 pmid: 16619257
130   Agung M, Ochi M, Yanada S, Adachi N, Izuta Y, Yamasaki T, et al. Mobilization of bone marrow-derived mesenchymal stem cells into the injured tissues after intraarticular injection and their contribution to tissue regeneration. Knee Surg Sports Traumatol Arthrosc 2006;14(12):1307–14
doi: 10.1007/s00167-006-0124-8 pmid: 16788809
131   Al Faqeh H, Nor Hamdan BM, Chen HC, Aminuddin BS, Ruszymah BH. 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 2012;47(6):458–64
doi: 10.1016/j.exger.2012.03.018 pmid: 22759409
132   Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician 2008;11(3):343–53
pmid: 18523506.
133   Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Regeneration of meniscus cartilage in a knee treated with percutaneously implanted autologous mesenchymal stem cells. Med Hypotheses 2008;71(6):900–8
doi: 10.1016/j.mehy.2008.06.042 pmid: 18786777
134   Centeno CJ, Schultz JR, Cheever M, Robinson B, Freeman M, Marasco W. Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique. Curr Stem Cell Res Ther 2010;5(1):81–93
doi: 10.2174/157488810790442796 pmid: 19951252
135   Davatchi F, Abdollahi BS, Mohyeddin M, Shahram F, Nikbin B. Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients. Int J Rheum Dis 2011;14(2):211–5
doi: 10.1111/j.1756-185X.2011.01599.x pmid: 21518322
136   Emadedin M, Aghdami N, Taghiyar L, Fazeli R, Moghadasali R, Jahangir S, et al. Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med 2012;15(7):422–8
pmid: 22724879.
137   Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, et al. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation 2013;95(12):1535–41
doi: 10.1097/TP.0b013e318291a2da pmid: 23680930
138   Soler R, Orozco L, Munar A, Huguet M, López R, Vives J, et al. Final results of a phase I-II trial using ex vivo expanded autologous mesenchymal stromal cells for the treatment of osteoarthritis of the knee confirming safety and suggesting cartilage regeneration. Knee 2016;23(4):647–54
doi: 10.1016/j.knee.2015.08.013 pmid: 26783191
139   Li J, Pei M. Cell senescence: a challenge in cartilage engineering and regeneration. Tissue Eng Part B Rev 2012;18(4):270–87
doi: 10.1089/ten.teb.2011.0583 pmid: 22273114
140   He F, Chen X, Pei M. Reconstruction of an in vitro tissue-specific microenvironment to rejuvenate synovium-derived stem cells for cartilage tissue engineering. Tissue Eng Part A 2009;15(12):3809–21
doi: 10.1089/ten.tea.2009.0188 pmid: 19545204
141   Diekman BO, Rowland CR, Lennon DP, Caplan AI, Guilak F. Chondrogenesis of adult stem cells from adipose tissue and bone marrow: induction by growth factors and cartilage-derived matrix. Tissue Eng Part A 2010;16(2):523–33
doi: 10.1089/ten.tea.2009.0398 pmid: 19715387
142   ter Huurne M, Schelbergen R, Blattes R, Blom A, de Munter W, Grevers LC, et al. Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum 2012;64(11):3604–13
doi: 10.1002/art.34626 pmid: 22961401
143   Toghraie F, Razmkhah M, Gholipour MA, Faghih Z, Chenari N, Torabi Nezhad S, et al. Scaffold-free adipose-derived stem cells (ASCs) improve experimentally induced osteoarthritis in rabbits. Arch Iran Med 2012;15(8):495–9
pmid: 22827787.
144   Vilar JM, Batista M, Morales M, Santana A, Cuervo B, Rubio M, et al. Assessment of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells in osteoarthritic dogs using a double blinded force platform analysis. BMC Vet Res 2014;10:143
doi: 10.1186/1746-6148-10-143 pmid: 24984756
145   Koh YG, Choi YJ, Kwon SK, Kim YS, Yeo JE. Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc 2015;23(5):1308–16
doi: 10.1007/s00167-013-2807-2 pmid: 24326779
146   Jo CH, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC, et al. Intra-minus;articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-minus;concept clinical trial. Stem Cells 2014;32(5):1254–66
doi: 10.1002/stem.1634 pmid: 24449146
147   Segawa Y, Muneta T, Makino H, Nimura A, Mochizuki T, Ju YJ, et al. Mesenchymal stem cells derived from synovium, meniscus, anterior cruciate ligament, and articular chondrocytes share similar gene expression profiles. J Orthop Res 2009;27(4):435–41
doi: 10.1002/jor.20786 pmid: 18973232
148   Fan J, Varshney RR, Ren L, Cai D, Wang DA. Synovium-derived mesenchymal stem cells: a new cell source for musculoskeletal regeneration. Tissue Eng Part B Rev 2009;15(1):75–86
doi: 10.1089/ten.teb.2008.0586 pmid: 19196118
149   Pei M, He F, Li J, Tidwell JE, Jones AC, McDonough EB. Repair of large animal partial-thickness cartilage defects through intraarticular injection of matrix-rejuvenated synovium-derived stem cells. Tissue Eng Part A 2013;19(9–10):1144–54
doi: 10.1089/ten.tea.2012.0351 pmid: 23216161
150   Mak J, Jablonski CL, Leonard CA, Dunn JF, Raharjo E, Matyas JR, et al. Intra-minus;articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model. Sci Rep 2016;6:23076
doi: 10.1038/srep23076 pmid: 26983696
151   Ozeki N, Muneta T, Koga H, Nakagawa Y, Mizuno M, Tsuji K, et al. Not single but periodic injections of synovial mesenchymal stem cells maintain viable cells in knees and inhibit osteoarthritis progression in rats. Osteoarthr Cartilage 2016;24(6):1061–70
doi: 10.1016/j.joca.2015.12.018 pmid: 26880531
[1] David F. Williams. Biocompatibility Pathways in Tissue-Engineering Templates[J]. Engineering, 2018, 4(2): 286 -290 .
[2] Alessandro Pistone, Daniela Iannazzo, Claudia Espro, Signorino Galvagno, Anna Tampieri, Monica Montesi, Silvia Panseri, Monica Sandri. Tethering of Gly-Arg-Gly-Asp-Ser-Pro-Lys Peptides on Mg-Doped Hydroxyapatite[J]. Engineering, 2017, 3(1): 55 -59 .
[3] Rúben F. Pereira, Paulo J. Bártolo. 3D Photo-Fabrication for Tissue Engineering and Drug Delivery[J]. Engineering, 2015, 1(1): 90 -112 .
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