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Modulation of Depth-dependent Properties in Tissue-engineered Cartilage with a Semi-permeable Membrane and Perfusion: A Continuum Model of Matrix Metabolism and Transport

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Abstract

The functional properties of cartilaginous tissues are determined predominantly by the content, distribution, and organization of proteoglycan and collagen in the extracellular matrix. Extracellular matrix accumulates in tissue-engineered cartilage constructs by metabolism and transport of matrix molecules, processes that are modulated by physical and chemical factors. Constructs incubated under free-swelling conditions with freely permeable or highly permeable membranes exhibit symmetric surface regions of soft tissue. The variation in tissue properties with depth from the surfaces suggests the hypothesis that the transport processes mediated by the boundary conditions govern the distribution of proteoglycan in such constructs. A continuum model (DiMicco and Sah in Transport Porus Med 50:57–73, 2003) was extended to test the effects of membrane permeability and perfusion on proteoglycan accumulation in tissue- engineered cartilage. The concentrations of soluble, bound, and degraded proteoglycan were analyzed as functions of time, space, and non-dimensional parameters for several experimental configurations. The results of the model suggest that the boundary condition at the membrane surface and the rate of perfusion, described by non-dimensional parameters, are important determinants of the pattern of proteoglycan accumulation. With perfusion, the proteoglycan profile is skewed, and decreases or increases in magnitude depending on the level of flow-based stimulation. Utilization of a semi-permeable membrane with or without unidirectional flow may lead to tissues with depth-increasing proteoglycan content, resembling native articular cartilage.

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References

  • Arner EC, Pratta MA, Trzaskos JM, Decicco CP, Tortorella MD (1999) Generation and characterization of aggrecanase. A soluble, cartilage-derived aggrecan-degrading activity. J Biol Chem 274:6594–6601

    Article  PubMed  Google Scholar 

  • Blanch HW, Clark DS (1996) Biochemical engineering. Marcel Dekker, New York

    Google Scholar 

  • Buckwalter JA, Mankin HJ (1997) Articular cartilage. Part I: tissue design and chondrocyte-matrix interactions. J Bone Joint Surg Am 79-A:600–611

    Google Scholar 

  • Buckwalter JA, Mankin HJ (1998) Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect 47:487–504

    PubMed  Google Scholar 

  • Buschmann MD, Gluzband YA, Grodzinsky AJ, Kimura JH, Hunziker EB (1992) Chondrocytes in agarose culture synthesize a mechanically functional extracellular matrix. J Orthop Res 10:745–758

    Article  PubMed  Google Scholar 

  • Chen SS, Falcovitz YH, Schneiderman R, Maroudas A, Sah RL (2001) Depth-dependent compressive properties of normal aged human femoral head articular cartilage. Osteoarthritis Cartilage 9:561–569

    Article  PubMed  Google Scholar 

  • Church RL, Pfeiffer SE, Tanzer ML (1971) Collagen biosynthesis: synthesis and secretion of a high molecular weight collagen precursor (procollagen). Proc Natl Acad Sci USA 68:2638–2642

    Article  PubMed  Google Scholar 

  • Comper WD, Williams RP (1987) Hydrodynamics of concentrated proteoglycan solutions. J Biol Chem 262:13464–13471

    PubMed  Google Scholar 

  • Davisson TH (2001) Biophysical regulation of metabolic balance in tissue engineered articular cartilage. University of California, San Diego, La Jolla

    Google Scholar 

  • Davisson TH, Sah RL, Ratcliffe AR (2002) Perfusion increases cell content and matrix synthesis in chondrocyte three-dimensional cultures. Tissue Eng 8:807–816

    Article  PubMed  Google Scholar 

  • DiMicco MA, Sah RL (2003) Dependence of cartilage matrix composition on biosynthesis, diffusion, and reaction. Transport Porous Med 50:57–73

    Article  Google Scholar 

  • Dunkelman NS, Zimber MP, LeBaron RG, Pavelec R, Kwan M, Purchio AF (1995) Cartilage production by rabbit articular chondrocytes on polyglycolic acid scaffolds in a closed bioreactor system. Biotechnol Bioeng 46:299–305

    Article  Google Scholar 

  • Freed LE, Langer R, Martin I, Pellis NR, Vunjak-Novakovic G (1997) Tissue engineering of cartilage in space. Proc Natl Acad Sci USA 94:13885–13890

    Article  PubMed  Google Scholar 

  • Galban CJ, Locke BR (1997) Analysis of cell growth in a polymer scaffold using a moving boundary approach. Biotechnol Bioeng 56:422–432

    Article  Google Scholar 

  • Gooch KJ, Kwon JH, Blunk T, Langer R, Freed LE, Vunjak-Novakovic G (2001) Effects of mixing intensity on tissue-engineered cartilage. Biotechnol Bioeng 72:402–407

    Article  PubMed  Google Scholar 

  • Grogan SP, Rieser F, Winkelmann V, Berardi S, Mainil-Varlet P (2003) A static, closed and scaffold-free bioreactor system that permits chondrogenesis in vitro. Osteoarthritis Cartilage 11:403–411

    Article  PubMed  Google Scholar 

  • Haddo O, Mahroof S, Higgs D, David L, Pringle J, Bayliss M, Cannon SR, Briggs TW (2004) The use of chondrogide membrane in autologous chondrocyte implantation. Knee 11:51–55

    Article  PubMed  Google Scholar 

  • Hascall VC, Luyten FP, Plaas AHK, Sandy JD (1990). Steady-state metabolism of proteoglycans in bovine articular cartilage. In: Maroudas A, Kuettner K (eds). Methods in Cartilage Research. Academic Press, San Diego

    Google Scholar 

  • Heywood HK, Sembi PK, Lee DA, Bader DL (2004) Cellular utilization determines viability and matrix distribution profiles in chondrocyte-seeded alginate constructs. Tissue Eng 10:1467–1479

    PubMed  Google Scholar 

  • Jennings L, Wu L, King KB, Hammerle H, Cs-Szabo G, Mollenhauer J (2001) The effects of collagen fragments on the extracellular matrix metabolism of bovine and human chondrocytes. Connect Tissue Res 42:71–86

    Article  PubMed  Google Scholar 

  • Klein TJ (2005) Cartilage tissue engineering: biophysical modulation of functional depth-dependent properties. University of California, San Diego, La Jolla, CA

    Google Scholar 

  • Klein TJ, Schumacher BL, Schmidt TA, Li KW, Voegtline MS, Masuda K, Thonar EJ-MA, Sah RL (2003) Tissue engineering of articular cartilage with stratification using chondrocyte subpopulations. Osteoarthritis Cartilage 11:595–602

    Article  PubMed  Google Scholar 

  • Klisch SM, Chen SS, Sah RL, Hoger A (2003) A growth mixture theory for cartilage with application to growth-related experiments on cartilage explants. J Biomech Eng 125:169–179

    Article  PubMed  Google Scholar 

  • Leddy HA, Awad HA, Guilak F (2004) Molecular diffusion in tissue-engineered cartilage constructs: effects of scaffold material, time, and culture conditions. J Biomed Mater Res 70B:397–406

    Article  Google Scholar 

  • Leddy HA, Guilak F (2003) Site-specific molecular diffusion in articular cartilage measured using fluorescence recovery after photobleaching. Ann Biomed Eng 31: 753–760

    Article  PubMed  Google Scholar 

  • Li KW, Klein TJ, Chawla K, Nugent GE, Bae WC, Sah RL (2004). In vitro physical stimulation of tissue-engineered and native cartilage. In: Sabatini M, DeCeuninck F, Pastoureau P (eds). Cartilage and osteoarthritis, vol 100. Humana Press, Totowa, NJ

    Google Scholar 

  • Masuda K, Sah RL, Hejna MJ, Thonar EJ-MA (2003) A novel two-step method for the formation of tissue engineered cartilage: the alginate-recovered-chondrocyte (ARC) method. J Orthop Res 21:139–148

    Google Scholar 

  • Mauck RL, Nicoll SB, Seyhan SL, Ateshian GA, Hung CT (2003) Synergistic action of growth factors and dynamic loading for articular cartilage tissue engineering. Tissue Eng 9:597–611

    Article  PubMed  Google Scholar 

  • Mauck RL, Soltz MA, Wang CC, Wong DD, Chao PH, Valhmu WB, Hung CT, Ateshian GA (2000) Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels. J Biomech Eng 122:252–260

    Article  PubMed  Google Scholar 

  • Menzel A (2005) Modelling of anisotropic growth in biological tissues: a new approach and computational aspects. Biomech Model Mechanobiol 3:147–171

    Article  PubMed  Google Scholar 

  • Mizuno S, Tateishi T, Ushida T, Glowacki J (2002) Hydrostatic fluid pressure enhances matrix synthesis and accumulation by bovine chondrocytes in three-dimensional culture. J Cell Physiol 193:319–327

    Article  PubMed  Google Scholar 

  • Mow VC, Guo XE (2002) Mechano-electrochemical properties of articular cartilage: their inhomogeneities and anisotropies. Annu Rev Biomed Eng 4:175–209

    Article  PubMed  Google Scholar 

  • Mow VC, Wang CC, Hung CT (1999) The extracellular matrix, interstitial fluid and ions as a mechanical signal transducer in articular cartilage. Osteoarthritis Cartilage 7:41–58

    Article  PubMed  Google Scholar 

  • Mow VC, Zhu W, Ratcliffe A (1991). Structure and function of articular cartilage and meniscus. In: Mow VC, Hayes WC (eds). Basic orthopaedic biomechanics. Raven Press, New York

    Google Scholar 

  • Ng KW, Wang CC, Mauck RL, Kelly TN, Chahine NO, Costa KD, Ateshian GA, Hung CT (2005) A layered agarose approach to fabricate depth-dependent inhomogeneity in chondrocyte-seeded constructs. J Orthop Res 23:134–141

    Article  PubMed  Google Scholar 

  • Obradovic B, Carrier RL, Vunjak-Novakovic G, Freed LE (1999) Gas exchance is essential for bioreactor cultivation of tissue engineered cartilage. Biotechnol Bioeng 63:197–205

    Article  PubMed  Google Scholar 

  • Obradovic B, Meldon JH, Freed LE, Vunjak-Novakovic G (2000) Glycosaminoglycan deposition in engineered cartilage: Experiments and mathematical model. AIChE J 46:1860–1871

    Article  Google Scholar 

  • Pazzano D, Mercier KA, Moran JM, Fong SS, DiBiasio DD, Rulfs JX, Kohles SS, Bonassar LJ (2000) Comparison of chondrogensis in static and perfused bioreactor culture. Biotechnol Prog 16:893–896

    Article  PubMed  Google Scholar 

  • Pei M, Solchaga LA, Seidel J, Zeng L, Vunjak-Novakovic G, Caplan AI, Freed LE (2002) Bioreactors mediate the effectiveness of tissue engineering scaffolds. FASEB J 16:1691–1694

    PubMed  Google Scholar 

  • Raimondi MT, Boschetti F, Falcone L, Migliavacca F, Remuzzi A, Dubini G (2004) The effect of media perfusion on three-dimensional cultures of human chondrocytes: integration of experimental and computational approaches. Biorheology 41:401–410

    PubMed  Google Scholar 

  • Riesle J, Hollander AP, Langer R, Freed LE, Vunjak-Novakovic G (1998) Collagen in tissue-engineered cartilage: types, structure, and crosslinks. J Cell Biochem 71:313–327

    Article  PubMed  Google Scholar 

  • Sah RL, Chen AC, Grodzinsky AJ, Trippel SB (1994) Differential effects of IGF-I and bFGF on matrix metabolism in calf and adult bovine cartilage explants. Arch Biochem Biophys 308:137–147

    Article  PubMed  Google Scholar 

  • Sah RL, Klein TJ, Schmidt TA, Albrecht DR, Bae WC, Nugent GE, McGowan KB, Temple MM, Jadin KD, Schumacher BL, Chen AC, Sandy JD (2004). Articular cartilage repair, regeneration, and replacement. In: Koopman WJ (eds). Arthritis and allied conditions: A Textbook of rheumatology. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  • Sandy JD, O’Neill JR, Ratzlaff LC (1989) Acquisition of hyaluronate-binding affinity in vivo by newly synthesized cartilage proteoglycans. Biochem J 258:875–880

    PubMed  Google Scholar 

  • Sandy JD, Plaas AHK (1986) Age-related changes in the kinetics of release of proteoglycans from normal rabbit cartilage explants. J Orthop Res 4:263–272

    Article  PubMed  Google Scholar 

  • Schinagl RM, Gurskis D, Chen AC, Sah RL (1997) Depth-dependent confined compression modulus of full-thickness bovine articular cartilage. J Orthop Res 15:499–506

    Article  PubMed  Google Scholar 

  • Smith RL, Carter DR, Schurman DJ (2004) Pressure and shear differentially alter human articular chondrocyte metabolism: a review. Clin Orthop S89–s95

  • Smith RL, Donlon BS, Gupta MK, Mohtai M, Das P, Carter DR, Cooke J, Gibbons G, Hutchinson N, Schurman DJ (1995) Effects of fluid-induced shear on articular chondrocyte morphology and metabolism in vitro. J Orthop Res 13:824–831

    Article  PubMed  Google Scholar 

  • Trindade MC, Shida J, Ikenoue T, Lee MS, Lin EY, Yaszay B, Yerby S, Goodman SB, Schurman DJ, Smith RL (2004) Intermittent hydrostatic pressure inhibits matrix metalloproteinase and pro-inflammatory mediator release from human osteoarthritic chondrocytes in vitro. Osteoarthritis Cartilage 12:729–735

    Article  PubMed  Google Scholar 

  • Vunjak-Novakovic G, Obradovic B, Martin I, Freed LE (2002) Bioreactor studies of native and tissue engineered cartilage. Biorheology 39:259–268

    PubMed  Google Scholar 

  • Wilson CG, Bonassar LJ, Kohles SS (2002) Modeling the dynamic composition of engineered cartilage. Arch Biochem Biophys 408:246–254

    Article  PubMed  Google Scholar 

  • Yellowley CE, Jacobs CR, Donahue HJ (1999) Mechanisms contributing to fluid-flow-induced 2+ mobilization in articular chondrocytes. J Cell Physiol 180:402–408

    Article  PubMed  Google Scholar 

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Klein, T.J., Sah, R.L. 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 6, 21–32 (2007). https://doi.org/10.1007/s10237-006-0045-y

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  • DOI: https://doi.org/10.1007/s10237-006-0045-y

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