J Knee Surg 2012; 25(03): 187-196
DOI: 10.1055/s-0032-1319783
Special Focus Section
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Toward Engineering a Biological Joint Replacement

Grace D. O'Connell
1   Department of Biomedical Engineering, Columbia University, New York
,
Eric G. Lima
2   Department of Mechanical Engineering, Cooper Union, New York
,
Liming Bian
3   Department of Mechanical & Automation Engineering, Biomedical Engineering Programme, The Chinese University of Hong Kong, Hong Kong
,
Nadeen O. Chahine
4   Department of Bioengineering, The Feinstein Institute for Medical Research, Manhasset, New York
,
Michael B. Albro
5   Department of Mechanical Engineering, Columbia University, New York
,
James L. Cook
6   Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri
,
Gerard A. Ateshian
5   Department of Mechanical Engineering, Columbia University, New York
,
Clark T. Hung
1   Department of Biomedical Engineering, Columbia University, New York
› Author Affiliations
Further Information

Publication History

09 October 2011

13 March 2012

Publication Date:
28 June 2012 (online)

Abstract

Osteoarthritis is a major cause of disability and pain for patients in the United States. Treatments for this degenerative disease represent a significant challenge considering the poor regenerative capacity of adult articular cartilage. Tissue-engineering techniques have advanced over the last two decades such that cartilage-like tissue can be cultivated in the laboratory for implantation. Even so, major challenges remain for creating fully functional tissue. This review article overviews some of these challenges, including overcoming limitations in nutrient supply to cartilage, improving in vitro collagen production, improving integration of engineered cartilage with native tissue, and exploring the potential for engineering full articular surface replacements.

 
  • References

  • 1 Helmick CG, Felson DT, Lawrence RC , et al; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum 2008; 58 (1) 15-25
  • 2 Brault MW, Helmick CG, Theis KA, Armour BS. Prevalence and Most Common Causes of Disability Among Adults—United States, 2005: CDC;2005..
  • 3 Dibonaventura M, Gupta S, McDonald M, Sadosky A. Evaluating the health and economic impact of osteoarthritis pain in the workforce: results from the National Health and Wellness Survey. BMC Musculoskelet Disord 2011; 12: 83
  • 4 Kotlarz H, Gunnarsson CL, Fang H, Rizzo JA. Insurer and out-of-pocket costs of osteoarthritis in the US: evidence from national survey data. Arthritis Rheum 2009; 60 (12) 3546-3553
  • 5 AAOS. Total Knee Replacement. 2009 ; http://orthoinfo.aaos.org/topic.cfm?topic=A00389 . Accessed August 9, 2011.
  • 6 Chong DY, Hansen UN, van der Venne R, Verdonschot N, Amis AA. The influence of tibial component fixation techniques on resorption of supporting bone stock after total knee replacement. J Biomech 2011; 44 (5) 948-954
  • 7 Essner A, Herrera L, Hughes P, Kester M. The influence of material and design on total knee replacement wear. J Knee Surg 2011; 24 (1) 9-17
  • 8 Lonner JH, Klotz M, Levitz C, Lotke PA. Changes in bone density after cemented total knee arthroplasty: influence of stem design. J Arthroplasty 2001; 16 (1) 107-111
  • 9 Naudie DD, Ammeen DJ, Engh GA, Rorabeck CH. Wear and osteolysis around total knee arthroplasty. J Am Acad Orthop Surg 2007; 15 (1) 53-64
  • 10 Pallante AL, Bae WC, Chen AC, Görtz S, Bugbee WD, Sah RL. Chondrocyte viability is higher after prolonged storage at 37 degrees C than at 4 degrees C for osteochondral grafts. Am J Sports Med 2009; 37 (Suppl. 01) 24S-32S
  • 11 Görtz S, Bugbee WD. Fresh osteochondral allografts: graft processing and clinical applications. J Knee Surg 2006; 19 (3) 231-240
  • 12 Mow VC, Lai M. Biorheology of swelling tissue. Biorheology 1990; 27 (1) 110-119
  • 13 Bian L, Zhai DY, Mauck RL, Burdick JA. Coculture of human mesenchymal stem cells and articular chondrocytes reduces hypertrophy and enhances functional properties of engineered cartilage. Tissue Eng Part A 2011; 17 (7–8) 1137-1145
  • 14 Hung CT, Mauck RL, Wang CC, Lima EG, Ateshian GA. A paradigm for functional tissue engineering of articular cartilage via applied physiologic deformational loading. Ann Biomed Eng 2004; 32 (1) 35-49
  • 15 Singhal AR, Agrawal CM, Athanasiou KA. Salient Degradation Features of a 50:50 PLA/PGA Scaffold for Tissue Engineering. Tissue Eng 1996; 2 (3) 197-207
  • 16 Elder SH, Cooley Jr AJ, Borazjani A, Sowell BL, To H, Tran SC. Production of hyaline-like cartilage by bone marrow mesenchymal stem cells in a self-assembly model. Tissue Eng Part A 2009; 15 (10) 3025-3036
  • 17 Natoli RM, Skaalure S, Bijlani S, Chen KX, Hu J, Athanasiou KA. Intracellular Na(+) and Ca(2+) modulation increases the tensile properties of developing engineered articular cartilage. Arthritis Rheum 2010; 62 (4) 1097-1107
  • 18 Selmi TA, Verdonk P, Chambat P , et al. Autologous chondrocyte implantation in a novel alginate-agarose hydrogel: outcome at two years. J Bone Joint Surg Br 2008; 90 (5) 597-604
  • 19 Zimmer Holdings and ISTO Technologies Announce Start of Neocartilage Clinical Trial. 2007; http://investor.zimmer.com/releasedetail.cfm?ReleaseID=230058 2010
  • 20 Niemeyer P, Köstler W, Salzmann GM, Lenz P, Kreuz PC, Südkamp NP. Autologous chondrocyte implantation for treatment of focal cartilage defects in patients age 40 years and older: A matched-pair analysis with 2-year follow-up. Am J Sports Med 2010; 38 (12) 2410-2416
  • 21 Filardo G, Kon E, Di Martino A, Iacono F, Marcacci M. Arthroscopic second-generation autologous chondrocyte implantation: a prospective 7-year follow-up study. Am J Sports Med 2011; 39 (10) 2153-2160
  • 22 Wegener B, Schrimpf FM, Bergschmidt P , et al. Cartilage regeneration by bone marrow cells-seeded scaffolds. J Biomed Mater Res A 2010; 95 (3) 735-740
  • 23 Connelly JT, Wilson CG, Levenston ME. Characterization of proteoglycan production and processing by chondrocytes and BMSCs in tissue engineered constructs. Osteoarthritis Cartilage 2008; 16 (9) 1092-1100
  • 24 Mauck RL, Soltz MA, Wang CC , et al. Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels. J Biomech Eng 2000; 122 (3) 252-260
  • 25 Ng KW, Lima EG, Bian L , et al. Passaged adult chondrocytes can form engineered cartilage with functional mechanical properties: a canine model. Tissue Eng Part A 2010; 16 (3) 1041-1051
  • 26 Moutos FT, Guilak F. Functional properties of cell-seeded three-dimensionally woven poly(epsilon-caprolactone) scaffolds for cartilage tissue engineering. Tissue Eng Part A 2010; 16 (4) 1291-1301
  • 27 Lee CH, Cook JL, Mendelson A, Moioli EK, Yao H, Mao JJ. Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study. Lancet 2010; 376 (9739) 440-448
  • 28 Bichara DA, Zhao X, Bodugoz-Senturk H , et al. Porous poly(vinyl alcohol)-hydrogel matrix-engineered biosynthetic cartilage. Tissue Eng Part A 2011; 17 (3-4) 301-309
  • 29 Laganà K, Moretti M, Dubini G, Raimondi MT. A new bioreactor for the controlled application of complex mechanical stimuli for cartilage tissue engineering. Proc Inst Mech Eng H 2008; 222 (5) 705-715
  • 30 Huang AH, Farrell MJ, Kim M, Mauck RL. Long-term dynamic loading improves the mechanical properties of chondrogenic mesenchymal stem cell-laden hydrogel. Eur Cell Mater 2010; 19: 72-85
  • 31 Qi Y, Zhao T, Xu K, Dai T, Yan W. The restoration of full-thickness cartilage defects with mesenchymal stem cells (MSCs) loaded and cross-linked bilayer collagen scaffolds on rabbit model. Mol Biol Rep 2012; 39: 1231-1237
  • 32 Jin CZ, Cho JH, Choi BH , et al. The Maturity of Tissue Engineered Cartilage in vitro Affects the Reparability for Osteochondral Defect. Tissue Eng Part A 2012; 18: 219
  • 33 Chahine NO, Albro MB, Lima EG , et al. Effect of dynamic loading on the transport of solutes into agarose hydrogels. Biophys J 2009; 97 (4) 968-975
  • 34 Chahine NO, Wei VI, Lima EG, Albro MB, Hung CT, Ateshian GA. Effect of perfusion and dynamic loading on the distribution and concentration of solutes in patellar shaped agarose constructs. Orthopaedic Research Society. 2006. Chicago:
  • 35 Lima EG, Bian L, Mauck RL , et al. The effect of applied compressive loading on tissue-engineered cartilage constructs cultured with TGF-beta3. Conf Proc IEEE Eng Med Biol Soc 2006; 1: 779-782
  • 36 Lima EG, Bian L, Ng KW , et al. The beneficial effect of delayed compressive loading on tissue-engineered cartilage constructs cultured with TGF-beta3. Osteoarthritis Cartilage 2007; 15 (9) 1025-1033
  • 37 Mauck RL, Hung CT, Ateshian GA. Modeling of neutral solute transport in a dynamically loaded porous permeable gel: implications for articular cartilage biosynthesis and tissue engineering. J Biomech Eng 2003; 125 (5) 602-614
  • 38 Mauck RL, Nicoll SB, Seyhan SL, Ateshian GA, Hung CT. Synergistic action of growth factors and dynamic loading for articular cartilage tissue engineering. Tissue Eng 2003; 9 (4) 597-611
  • 39 Mauck RL, Wang CC, Oswald ES, Ateshian GA, Hung CT. The role of cell seeding density and nutrient supply for articular cartilage tissue engineering with deformational loading. Osteoarthritis and cartilage/OARS . Osteoarthritis and Cartilage 2003; 11 (12) 879-890
  • 40 Treppo S, Koepp H, Quan EC, Cole AA, Kuettner KE, Grodzinsky AJ. Comparison of biomechanical and biochemical properties of cartilage from human knee and ankle pairs. J Orthop Res 2000; 18 (5) 739-748
  • 41 Nguyen AM, Levenston ME. Comparison of osmotic swelling influences on meniscal fibrocartilage and articular cartilage tissue mechanics in compression and shear. J Orthop Res 2012; 30: 95-102
  • 42 Mow VC, Huiskes R. Basic orthopaedics biomechanics and mechano-biology. Lippincott Williams & Wilkins; 2005
  • 43 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
  • 44 Temple-Wong MM, Bae WC, Chen MQ , et al. Biomechanical, structural, and biochemical indices of degenerative and osteoarthritic deterioration of adult human articular cartilage of the femoral condyle. Osteoarthritis Cartilage 2009; 17 (11) 1469-1476
  • 45 Stockwell RS. Biology of Cartilage Cells. Cambridge: Cambridge Press; 1979
  • 46 Choi JB, Youn I, Cao L , et al. Zonal changes in the three-dimensional morphology of the chondron under compression: the relationship among cellular, pericellular, and extracellular deformation in articular cartilage. J Biomech 2007; 40 (12) 2596-2603
  • 47 Guilak F, Ratcliffe A, Mow VC. Chondrocyte deformation and local tissue strain in articular cartilage: a confocal microscopy study. J Orthop Res 1995; 13 (3) 410-421
  • 48 Schinagl RM, Gurskis D, Chen AC, Sah RL. Depth-dependent confined compression modulus of full-thickness bovine articular cartilage. J Orthop Res 1997; 15 (4) 499-506
  • 49 Wang CC, Deng JM, Ateshian GA, Hung CT. An automated approach for direct measurement of two-dimensional strain distributions within articular cartilage under unconfined compression. J Biomech Eng 2002; 124 (5) 557-567
  • 50 Redman SN, Oldfield SF, Archer CW. Current strategies for articular cartilage repair. Eur Cell Mater 2005; 9: 23-32 , discussion 23–32
  • 51 Huang AH, Yeger-McKeever M, Stein A, Mauck RL. Tensile properties of engineered cartilage formed from chondrocyte- and MSC-laden hydrogels. Osteoarthritis Cartilage 2008; 16 (9) 1074-1082
  • 52 Mauck RL, Seyhan SL, Ateshian GA, Hung CT. Influence of seeding density and dynamic deformational loading on the developing structure/function relationships of chondrocyte-seeded agarose hydrogels. Ann Biomed Eng 2002; 30 (8) 1046-1056
  • 53 Bian L, Crivello KM, Ng KW , et al. Influence of temporary chondroitinase ABC-induced glycosaminoglycan suppression on maturation of tissue-engineered cartilage. Tissue Eng Part A 2009; 15 (8) 2065-2072
  • 54 Pei M, He F, Boyce BM, Kish VL. Repair of full-thickness femoral condyle cartilage defects using allogeneic synovial cell-engineered tissue constructs. Osteoarthritis Cartilage 2009; 17 (6) 714-722
  • 55 Sampat SR, O'Connell GD, Fong JV, Alegre-Aguarón E, Ateshian GA, Hung CT. Growth factor priming of synovium-derived stem cells for cartilage tissue engineering. Tissue Eng Part A 2011; 17 (17-18) 2259-2265
  • 56 Gimble JM, Bunnell BA, Chiu ES, Guilak F. Concise review: Adipose-derived stromal vascular fraction cells and stem cells: let's not get lost in translation. Stem Cells 2011; 29 (5) 749-754
  • 57 Sundelacruz S, Kaplan DL. Stem cell- and scaffold-based tissue engineering approaches to osteochondral regenerative medicine. Semin Cell Dev Biol 2009; 20 (6) 646-655
  • 58 Nishimura K, Solchaga LA, Caplan AI, Yoo JU, Goldberg VM, Johnstone B. Chondroprogenitor cells of synovial tissue. Arthritis Rheum 1999; 42 (12) 2631-2637
  • 59 De Ugarte DA, Alfonso Z, Zuk PA , et al. Differential expression of stem cell mobilization-associated molecules on multi-lineage cells from adipose tissue and bone marrow. Immunol Lett 2003; 89 (2-3) 267-270
  • 60 Noël D, Caton D, Roche S , et al. Cell specific differences between human adipose-derived and mesenchymal-stromal cells despite similar differentiation potentials. Exp Cell Res 2008; 314 (7) 1575-1584
  • 61 Martínez-Lorenzo MJ, Royo-Cañas M, Alegre-Aguarón E , et al. Phenotype and chondrogenic differentiation of mesenchymal cells from adipose tissue of different species. J Orthop Res 2009; 27 (11) 1499-1507
  • 62 Pei M, He F, Vunjak-Novakovic G. Synovium-derived stem cell-based chondrogenesis. Differentiation 2008; 76 (10) 1044-1056
  • 63 Huang AH, Stein A, Tuan RS, Mauck RL. Transient exposure to transforming growth factor beta 3 improves the mechanical properties of mesenchymal stem cell-laden cartilage constructs in a density-dependent manner. Tissue Eng Part A 2009; 15 (11) 3461-3472
  • 64 Anderson DE, Athanasiou KA. A comparison of primary and passaged chondrocytes for use in engineering the temporomandibular joint. Arch Oral Biol 2009; 54 (2) 138-145
  • 65 Kelly TA, Ng KW, Wang CC, Ateshian GA, Hung CT. Spatial and temporal development of chondrocyte-seeded agarose constructs in free-swelling and dynamically loaded cultures. J Biomech 2006; 39 (8) 1489-1497
  • 66 Ateshian GA, Soslowsky LJ, Mow VC. Quantitation of articular surface topography and cartilage thickness in knee joints using stereophotogrammetry. J Biomech 1991; 24 (8) 761-776
  • 67 Eckstein F, Gavazzeni A, Sittek H , et al. Determination of knee joint cartilage thickness using three-dimensional magnetic resonance chondro-crassometry (3D MR-CCM). Magn Reson Med 1996; 36 (2) 256-265
  • 68 Wilsman NJ, Van Sickle DC. Cartilage canals, their morphology and distribution. Anat Rec 1972; 173 (1) 79-93
  • 69 Stockwell RA. The ultrastructure of cartilage canals and the surrounding cartilage in the sheep fetus. J Anat 1971; 109 (Pt 3) 397-410
  • 70 Hunt CD, Ollerich DA, Nielsen FH. Morphology of the perforating cartilage canals in the proximal tibial growth plate of the chick. Anat Rec 1979; 194 (1) 143-157
  • 71 Ytrehus B, Carlson CS, Lundeheim N , et al. Vascularisation and osteochondrosis of the epiphyseal growth cartilage of the distal femur in pigs—development with age, growth rate, weight and joint shape. Bone 2004; 34 (3) 454-465
  • 72 Albro MB, Banerjee RE, Li R , et al. Dynamic loading of immature epiphyseal cartilage pumps nutrients out of vascular canals. J Biomech 2011; 44 (9) 1654-1659
  • 73 Albro MB, Chahine NO, Li R, Yeager K, Hung CT, Ateshian GA. Dynamic loading of deformable porous media can induce active solute transport. J Biomech 2008; 41 (15) 3152-3157
  • 74 Waldman SD, Spiteri CG, Grynpas MD, Pilliar RM, Kandel RA. Long-term intermittent compressive stimulation improves the composition and mechanical properties of tissue-engineered cartilage. Tissue Eng 2004; 10 (9-10) 1323-1331
  • 75 Ng KW, Mauck RL, Wang CC , et al. Duty Cycle of Deformational Loading Influences the Growth of Engineered Articular Cartilage. Cell Mol Bioeng 2009; 2 (3) 386-394
  • 76 Waldman SD, Spiteri CG, Grynpas MD, Pilliar RM, Hong J, Kandel RA. Effect of biomechanical conditioning on cartilaginous tissue formation in vitro. J Bone Joint Surg Am 2003; 85-A (Suppl. 02) 101-105
  • 77 Raimondi MT, Boschetti F, Falcone L, Migliavacca F, Remuzzi A, Dubini G. The effect of media perfusion on three-dimensional cultures of human chondrocytes: integration of experimental and computational approaches. Biorheology 2004; 41 (3–4) 401-410
  • 78 Raimondi MT, Candiani G, Cabras M , et al. Engineered cartilage constructs subject to very low regimens of interstitial perfusion. Biorheology 2008; 45 (3–4) 471-478
  • 79 Grayson WL, Bhumiratana S, Grace Chao PH, Hung CT, Vunjak-Novakovic G. Spatial regulation of human mesenchymal stem cell differentiation in engineered osteochondral constructs: effects of pre-differentiation, soluble factors and medium perfusion. Osteoarthritis Cartilage 2010; 18 (5) 714-723
  • 80 Seidel JO, Pei M, Gray ML, Langer R, Freed LE, Vunjak-Novakovic G. Long-term culture of tissue engineered cartilage in a perfused chamber with mechanical stimulation. Biorheology 2004; 41 (3–4) 445-458
  • 81 Bian L, Angione SL, Ng KW , et al. Influence of decreasing nutrient path length on the development of engineered cartilage. Osteoarthritis Cartilage 2009; 17 (5) 677-685
  • 82 Choi NW, Cabodi M, Held B, Gleghorn JP, Bonassar LJ, Stroock AD. Microfluidic scaffolds for tissue engineering. Nat Mater 2007; 6 (11) 908-915
  • 83 Ling Y, Rubin J, Deng Y , et al. A cell-laden microfluidic hydrogel. Lab Chip 2007; 7 (6) 756-762
  • 84 Golden AP, Tien J. Fabrication of microfluidic hydrogels using molded gelatin as a sacrificial element. Lab Chip 2007; 7 (6) 720-725
  • 85 O'Connell GD, Gollnick C, Ateshian GA, Bellamkonda RV, Hung CT. Beneficial effects of chondroitinase ABC release from lipid microtubes encapsulated in chondrocytes-seeded hydrogel constructs. Paper presented at: ASME2011 Summer Bioengineering Conference 2011; Farmington, PA
  • 86 Wang X, Wenk E, Zhang X, Meinel L, Vunjak-Novakovic G, Kaplan DL. Growth factor gradients via microsphere delivery in biopolymer scaffolds for osteochondral tissue engineering. J Control Release 2009; 134 (2) 81-90
  • 87 Durney KM, Sirsi SR, Nover A , et al. Using Microbubbles to Modulate Hydrogel Scaffold Properties for Cartilage Tissue Engineering. Paper presented at: Orthopaedic Research Society 2010; San Diego, CA.
  • 88 Durney KM, Sirsi SR, Nover A , et al. Microbubbles Improve Depth-Dependent Mechanical Properties of Cartilage Tissue Engineered Constructs. Orthopaedic Research Society 2011; Long Beach, CA
  • 89 Chen CC, Borden MA. The role of poly(ethylene glycol) brush architecture in complement activation on targeted microbubble surfaces. Biomaterials 2011; 32 (27) 6579-6587
  • 90 Lee H, McKeon RJ, Bellamkonda RV. Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury. Proc Natl Acad Sci U S A 2010; 107 (8) 3340-3345
  • 91 Wang X, Yucel T, Lu Q, Hu X, Kaplan DL. Silk nanospheres and microspheres from silk/pva blend films for drug delivery. Biomaterials 2010; 31 (6) 1025-1035
  • 92 Meilander NJ, Yu X, Ziats NP, Bellamkonda RV. Lipid-based microtubular drug delivery vehicles. J Control Release 2001; 71 (1) 141-152
  • 93 Asanbaeva A, Masuda K, Thonar EJ, Klisch SM, Sah RL. Mechanisms of cartilage growth: modulation of balance between proteoglycan and collagen in vitro using chondroitinase ABC. Arthritis Rheum 2007; 56 (1) 188-198
  • 94 Ng KW, Kugler LE, Doty SB, Ateshian GA, Hung CT. Scaffold degradation elevates the collagen content and dynamic compressive modulus in engineered articular cartilage. Osteoarthritis Cartilage 2009; 17 (2) 220-227
  • 95 Natoli RM, Revell CM, Athanasiou KA. Chondroitinase ABC treatment results in greater tensile properties of self-assembled tissue-engineered articular cartilage. Tissue Eng Part A 2009; 15 (10) 3119-3128
  • 96 Natoli RM, Responte DJ, Lu BY, Athanasiou KA. Effects of multiple chondroitinase ABC applications on tissue engineered articular cartilage. J Orthop Res 2009; 27 (7) 949-956
  • 97 O'Connell GD, Fong JV, Joffe A, Moy MY, Newman IB, Hung CT. Trimethylamine N-oxide enhances the mechanical and biochemical properties of tissue engineered cartilage. Paper presented at: Orthopaedic Research Society 2011; Long Beach, CA.
  • 98 Ifkovits JL, Devlin JJ, Eng G, Martens TP, Vunjak-Novakovic G, Burdick JA. Biodegradable fibrous scaffolds with tunable properties formed from photo-cross-linkable poly(glycerol sebacate). ACS Appl Mater Interfaces 2009; 1 (9) 1878-1886
  • 99 Wu JP, Kirk TB, Zheng MH. Study of the collagen structure in the superficial zone and physiological state of articular cartilage using a 3D confocal imaging technique. J Orthop Surg 2008; 3: 29
  • 100 Wong BL, Sah RL. Mechanical asymmetry during articulation of tibial and femoral cartilages: local and overall compressive and shear deformation and properties. J Biomech 2010; 43 (9) 1689-1695
  • 101 Guthold M, Liu W, Sparks EA , et al. A comparison of the mechanical and structural properties of fibrin fibers with other protein fibers. Cell Biochem Biophys 2007; 49 (3) 165-181
  • 102 Cinbiz MN, Tığli RS, Beşkardeş IG, Gümüşderelioğlu M, Colak U. Computational fluid dynamics modeling of momentum transport in rotating wall perfused bioreactor for cartilage tissue engineering. J Biotechnol 2010; 150 (3) 389-395
  • 103 Vunjak-Novakovic G, Martin I, Obradovic B , et al. Bioreactor cultivation conditions modulate the composition and mechanical properties of tissue-engineered cartilage. J Orthop Res 1999; 17 (1) 130-138
  • 104 Klein TJ, Sah RL. Modulation of depth-dependent properties in tissue-engineered cartilage with a semi-permeable membrane and perfusion: a continuum model of matrix metabolism and transport. Biomech Model Mechanobiol 2007; 6 (1-2) 21-32
  • 105 Darling EM, Athanasiou KA. Articular cartilage bioreactors and bioprocesses. Tissue Eng 2003; 9 (1) 9-26