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From Repair to Regeneration: Biomaterials to Reprogram the Meniscus Wound Microenvironment

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Abstract

When the field of tissue engineering first arose, scaffolds were conceived of as inert three-dimensional structures whose primary function was to support cellularity and tissue growth. Since then, advances in scaffold and biomaterial design have evolved to not only guide tissue formation, but also to interact dynamically with and manipulate the wound environment. At present, these efforts are being directed towards strategies that directly address limitations in endogenous wound repair, with the goal of reprogramming the local wound environment (and the cells within that locality) from a state that culminates in an inferior tissue repair into a state in which functional regeneration is achieved. This review will address this approach with a focus on recent advances in scaffold design towards the resolution of tears of the knee meniscus as a case example. The inherent limitations to endogenous repair will be discussed, as will specific examples of how biomaterials are being designed to overcome these limitations. Examples will include design of fibrous scaffolds that promote colonization by modulating local extracellular matrix density and delivering recruitment factors. Furthermore, we will discuss scaffolds that are themselves modulated by the wound environment to alter porosity and modulate therapeutic release through precise coordination of scaffold degradation. Finally, we will close with emerging concepts in local control of cell mechanics to improve interstitial cell migration and so advance repair. Overall, these examples will illustrate how emergent features within a biomaterial can be tuned to manipulate and harness the local tissue microenvironment in order to promote robust regeneration.

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References

  1. Adams, M. E., and D. W. L. Hukins. The extracellular matrix of the meniscus. In: Knee Meniscus: Basic and Clinical Foundations, edited by V. C. Mow, S. P. Arnoczky, and D. W. Jackson. New York: Raven Press, Ltd., 1992, pp. 15–28.

    Google Scholar 

  2. Ahmed, A. M. The load-bearing role of the knee meniscus. In: Knee Meniscus: Basic and Clinical Foundations, edited by V. C. Mow, S. P. Arnoczky, and D. W. Jackson. New York: Raven Press, Ltd., 1992, pp. 59–73.

    Google Scholar 

  3. Andrish, J. T. Meniscal injuries in children and adolescents: diagnosis and management. J. Am. Acad. Orthop. Surg. 4:231–237, 1996.

    PubMed  Google Scholar 

  4. Arnoczky, S. P., and R. F. Warren. Microvasculature of the human meniscus. Am. J. Sports Med. 10:90–95, 1982.

    CAS  PubMed  Google Scholar 

  5. Baker, B. M., A. O. Gee, R. B. Metter, A. S. Nathan, R. A. Marklein, J. A. Burdick, et al. The potential to improve cell infiltration in composite fiber-aligned electrospun scaffolds by the selective removal of sacrificial fibers. Biomaterials 29:2348–2358, 2008.

    PubMed Central  CAS  PubMed  Google Scholar 

  6. Baker, B. M., and R. L. Mauck. The effect of nanofiber alignment on the maturation of engineered meniscus constructs. Biomaterials 28:1967–1977, 2007.

    PubMed Central  CAS  PubMed  Google Scholar 

  7. Baker, B. M., N. L. Nerurkar, J. A. Burdick, D. M. Elliott, and R. L. Mauck. Fabrication and modeling of dynamic multipolymer nanofibrous scaffolds. J. Biomech. Eng. 131:101012, 2009.

    PubMed Central  PubMed  Google Scholar 

  8. Baker, B. M., R. P. Shah, A. H. Huang, and R. L. Mauck. Dynamic tensile loading improves the functional properties of mesenchymal stem cell-laden nanofiber-based fibrocartilage. Tissue Eng. Part A 17:1445–1455, 2011.

    PubMed Central  CAS  PubMed  Google Scholar 

  9. Baker, B. M., R. P. Shah, A. M. Silverstein, J. L. Esterhai, J. A. Burdick, and R. L. Mauck. Sacrificial nanofibrous composites provide instruction without impediment and enable functional tissue formation. Proc. Natl. Acad. Sci. USA 109:14176–14181, 2012.

    PubMed Central  CAS  PubMed  Google Scholar 

  10. Barrett, G. R., M. H. Field, S. H. Treacy, and C. G. Ruff. Clinical results of meniscus repair in patients 40 years and older. Arthroscopy 14:824–829, 1998.

    CAS  PubMed  Google Scholar 

  11. Bartova, E., J. Krejci, A. Harnicarova, and S. Kozubek. Differentiation of human embryonic stem cells induces condensation of chromosome territories and formation of heterochromatin protein 1 foci. Differentiation 76:24–32, 2008.

    CAS  PubMed  Google Scholar 

  12. Beredjiklian, P. K., M. Favata, J. S. Cartmell, C. L. Flanagan, T. M. Crombleholme, and L. J. Soslowsky. Regenerative versus reparative healing in tendon: a study of biomechanical and histological properties in fetal sheep. Ann. Biomed. Eng. 31:1143–1152, 2003.

    PubMed  Google Scholar 

  13. Bhattacharya, D., S. Talwar, A. Mazumder, and G. V. Shivashankar. Spatio-temporal plasticity in chromatin organization in mouse cell differentiation and during Drosophila embryogenesis. Biophys. J . 96:3832–3839, 2009.

    PubMed Central  CAS  PubMed  Google Scholar 

  14. Booth-Gauthier, E. A., V. Du, M. Ghibaudo, A. D. Rape, K. N. Dahl, and B. Ladoux. Hutchinson-Gilford progeria syndrome alters nuclear shape and reduces cell motility in three dimensional model substrates. Integr. Biol. (Camb.) 5:569–577, 2013.

    CAS  Google Scholar 

  15. Bott, K., Z. Upton, K. Schrobback, M. Ehrbar, J. A. Hubbell, M. P. Lutolf, et al. The effect of matrix characteristics on fibroblast proliferation in 3D gels. Biomaterials 31:8454–8464, 2010.

    CAS  PubMed  Google Scholar 

  16. Burdick, J. A., and W. L. Murphy. Moving from static to dynamic complexity in hydrogel design. Nat. Commun. 3:1269, 2012.

    PubMed  Google Scholar 

  17. Clark, C. R., and J. A. Ogden. Development of the menisci of the human knee joint. Morphological changes and their potential role in childhood meniscal injury. J. Bone Joint Surg. Am. 65:538–547, 1983.

    CAS  PubMed  Google Scholar 

  18. Connelly, J. T., A. J. Garcia, and M. E. Levenston. Interactions between integrin ligand density and cytoskeletal integrity regulate BMSC chondrogenesis. J. Cell. Physiol. 217:145–154, 2008.

    CAS  PubMed  Google Scholar 

  19. Dahl, K. N., A. J. Engler, J. D. Pajerowski, and D. E. Discher. Power-law rheology of isolated nuclei with deformation mapping of nuclear substructures. Biophys. J . 89:2855–2864, 2005.

    PubMed Central  CAS  PubMed  Google Scholar 

  20. Dahl, K. N., A. J. Ribeiro, and J. Lammerding. Nuclear shape, mechanics, and mechanotransduction. Circ. Res. 102:1307–1318, 2008.

    PubMed Central  CAS  PubMed  Google Scholar 

  21. Dai, M., Y. Yang, I. Omelchenko, A. L. Nuttall, A. Kachelmeier, R. Xiu, et al. Bone marrow cell recruitment mediated by inducible nitric oxide synthase/stromal cell-derived factor-1alpha signaling repairs the acoustically damaged cochlear blood-labyrinth barrier. Am. J. Pathol. 177:3089–3099, 2010.

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Day, B., W. G. Mackenzie, S. S. Shim, and G. Leung. The vascular and nerve supply of the human meniscus. Arthroscopy 1:58–62, 1985.

    CAS  PubMed  Google Scholar 

  23. Dourte, L. M., A. F. Kuntz, and L. J. Soslowsky. Twenty-five years of tendon and ligament research. J. Orthop. Res. 26:1297–1305, 2008.

    PubMed  Google Scholar 

  24. Doyle, A. D., R. J. Petrie, M. L. Kutys, and K. M. Yamada. Dimensions in cell migration. Curr. Opin. Cell Biol. 25:642–649, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  25. Eckhouse, S. R., B. P. Purcell, J. R. McGarvey, D. Lobb, C. B. Logdon, H. Doviak, et al. Local hydrogel release of recombinant TIMP-3 attenuates adverse left ventricular remodeling after experimental myocardial infarction. Sci. Transl. Med. 6:223ra21, 2014.

    PubMed Central  PubMed  Google Scholar 

  26. Eggli, S., H. Wegmuller, J. Kosina, C. Huckell, and R. P. Jakob. Long-term results of arthroscopic meniscal repair. An analysis of isolated tears. Am. J. Sports Med. 23:715–720, 1995.

    CAS  PubMed  Google Scholar 

  27. Engler, A. J., S. Sen, H. L. Sweeney, and D. E. Discher. Matrix elasticity directs stem cell lineage specification. Cell 126:677–689, 2006.

    CAS  PubMed  Google Scholar 

  28. Favata, M., P. K. Beredjiklian, M. H. Zgonis, D. P. Beason, T. M. Crombleholme, A. F. Jawad, et al. Regenerative properties of fetal sheep tendon are not adversely affected by transplantation into an adult environment. J. Orthop. Res. 24:2124–2132, 2006.

    PubMed  Google Scholar 

  29. Fisher, M. B., E. A. Henning, N. Soegaard, J. L. Esterhai, and R. L. Mauck. Organized nanofibrous scaffolds that mimic the macroscopic and microscopic architecture of the knee meniscus. Acta Biomater. 9:4496–4504, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  30. Friedl, P., E. Sahai, S. Weiss, and K. M. Yamada. New dimensions in cell migration. Nat. Rev. Mol. Cell Biol. 13:743–747, 2012.

    CAS  PubMed  Google Scholar 

  31. Friedl, P., K. Wolf, and J. Lammerding. Nuclear mechanics during cell migration. Curr. Opin. Cell Biol. 23:55–64, 2011.

    PubMed Central  CAS  PubMed  Google Scholar 

  32. Fu, Y., L. K. Chin, T. Bourouina, A. Q. Liu, and A. M. VanDongen. Nuclear deformation during breast cancer cell transmigration. Lab Chip 12:3774–3778, 2012.

    CAS  PubMed  Google Scholar 

  33. Greiner, A. M., M. Jackel, A. C. Scheiwe, D. R. Stamow, T. J. Autenrieth, J. Lahann, et al. Multifunctional polymer scaffolds with adjustable pore size and chemoattractant gradients for studying cell matrix invasion. Biomaterials 35:611–619, 2014.

    CAS  PubMed  Google Scholar 

  34. Greis, P. E., M. C. Holmstrom, D. D. Bardana, and R. T. Burks. Meniscal injury: II. Management. J. Am. Acad. Orthop. Surg. 10:177–187, 2002.

    PubMed  Google Scholar 

  35. Guilak, F., J. R. Tedrow, and R. Burgkart. Viscoelastic properties of the cell nucleus. Biochem. Biophys. Res. Commun. 269:781–786, 2000.

    CAS  PubMed  Google Scholar 

  36. Han, W. M., S. J. Heo, T. P. Driscoll, L. J. Smith, R. L. Mauck, and D. M. Elliott. Macro- to microscale strain transfer in fibrous tissues is heterogeneous and tissue-specific. Biophys. J . 105:807–817, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  37. Harada, T., J. Swift, J. Irianto, J. W. Shin, K. R. Spinler, A. Athirasala, et al. Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival. J. Cell Biol. 204:669–682, 2014.

    PubMed Central  CAS  PubMed  Google Scholar 

  38. Hennerbichler, A., F. Moutos, D. Hennerbichler, B. Fermor, J. B. Weinberg, and F. Guilak. Inhibition of integrative repair of the meniscus in vitro by interleukin-1 and tumor necrosis factor alpha. Trans. ORS 31:1038, 2006.

    Google Scholar 

  39. Hennerbichler, A., F. T. Moutos, D. Hennerbichler, J. B. Weinberg, and F. Guilak. Interleukin-1 and tumor necrosis factor alpha inhibit repair of the porcine meniscus in vitro. Osteoarthritis Cartilage 15:1053–1060, 2007.

    PubMed Central  CAS  PubMed  Google Scholar 

  40. Heo, S. J., T. P. Driscoll, S. D. Thorpe, W. M. Han, D. M. Elliott, D. A. Lee, et al. Rapid chromatin condensation increases stem cell nuclear mechanics and mechanosensitivity. Trans. Orthop. Res. Soc. 60:457, 2014.

  41. Heo, S. J., N. L. Nerurkar, B. M. Baker, J. W. Shin, D. M. Elliott, and R. L. Mauck. Fiber stretch and reorientation modulates mesenchymal stem cell morphology and fibrous gene expression on oriented nanofibrous microenvironments. Ann. Biomed. Eng. 39:2780–2790, 2011.

    PubMed Central  PubMed  Google Scholar 

  42. Heo, S. J., S. D. Thorpe, T. P. Driscoll, S. K. Hashmi, D. A. Lee, and R. L. Mauck. Rapid and sustained changes in nuclear architecture and mechanics in mesenchymal stem cells in response to dynamic stretch. Trans. Orthop. Res. Soc. 60:180, 2014.

  43. Ho, C. Y., and J. Lammerding. Lamins at a glance. J. Cell Sci. 125:2087–2093, 2012.

    PubMed Central  CAS  PubMed  Google Scholar 

  44. Ifkovits, J. L., K. Wu, R. L. Mauck, and J. A. Burdick. The influence of fibrous elastomer structure and porosity on matrix organization. PLoS ONE 5:e15717, 2010.

    PubMed Central  CAS  PubMed  Google Scholar 

  45. Imler, S. M., A. N. Doshi, and M. E. Levenston. Combined effects of growth factors and static mechanical compression on meniscus explant biosynthesis. Osteoarthritis Cartilage 12:736–744, 2004.

    PubMed  Google Scholar 

  46. Ionescu, L. C., G. C. Lee, G. H. Garcia, T. L. Zachry, R. P. Shah, B. J. Sennett, et al. Maturation state-dependent alterations in meniscus integration: implications for scaffold design and tissue engineering. Tissue Eng. Part A 17:193–204, 2011.

    PubMed Central  CAS  PubMed  Google Scholar 

  47. Ionescu, L. C., G. C. Lee, B. J. Sennett, J. A. Burdick, and R. L. Mauck. An anisotropic nanofiber/microsphere composite with controlled release of biomolecules for fibrous tissue engineering. Biomaterials 31:4113–4120, 2010.

    PubMed Central  CAS  PubMed  Google Scholar 

  48. Ionescu, L. C., and R. L. Mauck. Porosity and cell preseeding influence electrospun scaffold maturation and meniscus integration in vitro. Tissue Eng. Part A 19:538–547, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  49. Kambic, H. E., H. Futani, and C. A. McDevitt. Cell, matrix changes and alpha-smooth muscle actin expression in repair of the canine meniscus. Wound Repair Regen. 8:554–561, 2000.

    CAS  PubMed  Google Scholar 

  50. Khetan, S., and J. A. Burdick. Patterning network structure to spatially control cellular remodeling and stem cell fate within 3-dimensional hydrogels. Biomaterials 31:8228–8234, 2010.

    CAS  PubMed  Google Scholar 

  51. Khetan, S., M. Guvendiren, W. R. Legant, D. M. Cohen, C. S. Chen, and J. A. Burdick. Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels. Nat. Mater. 12:458–465, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  52. Kim, I. L., M. B. Fisher, B. M. Baker, R. L. Mauck, and J. A. Burdick. Tunable fibrous hyaluronic acid scaffolds for cartilage tissue engineering. In: Transactions of the Society for Biomaterials Annual Meeting, 2014.

  53. Kim, I. L., S. Khetan, B. M. Baker, C. S. Chen, and J. A. Burdick. Fibrous hyaluronic acid hydrogels that direct MSC chondrogenesis through mechanical and adhesive cues. Biomaterials 34:5571–5580, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  54. Kim, I. L., R. L. Mauck, and J. A. Burdick. Hydrogel design for cartilage tissue engineering: a case study with hyaluronic acid. Biomaterials 32:8771–8782, 2011.

    PubMed Central  CAS  PubMed  Google Scholar 

  55. Kolambkar, Y. M., K. M. Dupont, J. D. Boerckel, N. Huebsch, D. J. Mooney, D. W. Hutmacher, et al. An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects. Biomaterials 32:65–74, 2011.

    PubMed Central  CAS  PubMed  Google Scholar 

  56. Krause, M., J. Te Riet, and K. Wolf. Probing the compressibility of tumor cell nuclei by combined atomic force-confocal microscopy. Phys. Biol. 10:065002, 2013.

    PubMed  Google Scholar 

  57. Krejci, J., R. Uhlirova, G. Galiova, S. Kozubek, J. Smigova, and E. Bartova. Genome-wide reduction in H3K9 acetylation during human embryonic stem cell differentiation. J. Cell. Physiol. 219:677–687, 2009.

    CAS  PubMed  Google Scholar 

  58. Lammerding, J. Mechanics of the nucleus. Compr. Physiol. 1:783–807, 2011.

    PubMed  Google Scholar 

  59. Lammerding, J., L. G. Fong, J. Y. Ji, K. Reue, C. L. Stewart, S. G. Young, et al. Lamins A and C but not lamin B1 regulate nuclear mechanics. J. Biol. Chem. 281:25768–25780, 2006.

    CAS  PubMed  Google Scholar 

  60. Lammerding, J., and R. T. Lee. The nuclear membrane and mechanotransduction: impaired nuclear mechanics and mechanotransduction in lamin A/C deficient cells. Novartis Found. Symp. 264:264–273, 2005; ((discussion 73–8)).

    CAS  PubMed  Google Scholar 

  61. Lammerding, J., P. C. Schulze, T. Takahashi, S. Kozlov, T. Sullivan, R. D. Kamm, et al. Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J. Clin. Invest. 113:370–378, 2004.

    PubMed Central  CAS  PubMed  Google Scholar 

  62. Lange, J. R., and B. Fabry. Cell and tissue mechanics in cell migration. Exp. Cell Res. 319:2418–2423, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  63. Lee, C. H., J. L. Cook, A. Mendelson, E. K. Moioli, H. Yao, and J. J. Mao. Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study. Lancet 376:440–448, 2010.

    PubMed Central  CAS  PubMed  Google Scholar 

  64. Li, W. J., C. T. Laurencin, E. J. Caterson, R. S. Tuan, and F. K. Ko. Electrospun nanofibrous structure: a novel scaffold for tissue engineering. J. Biomed. Mater. Res. 60:613–621, 2002.

    CAS  PubMed  Google Scholar 

  65. Li, W. J., R. L. Mauck, J. A. Cooper, X. Yuan, and R. S. Tuan. Engineering controllable anisotropy in electrospun biodegradable nanofibrous scaffolds for musculoskeletal tissue engineering. J. Biomech. 40:1686–1693, 2007.

    PubMed Central  PubMed  Google Scholar 

  66. Loeser, R. F., S. R. Goldring, C. R. Scanzello, and M. B. Goldring. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 64:1697–1707, 2012.

    PubMed Central  PubMed  Google Scholar 

  67. Lohmander, L. S., K. D. Brandt, S. A. Mazzuca, B. P. Katz, S. Larsson, A. Struglics, et al. Use of the plasma stromelysin (matrix metalloproteinase 3) concentration to predict joint space narrowing in knee osteoarthritis. Arthritis Rheum. 52:3160–3167, 2005.

    CAS  PubMed  Google Scholar 

  68. Makris, E. A., P. Hadidi, and K. A. Athanasiou. The knee meniscus: structure-function, pathophysiology, current repair techniques, and prospects for regeneration. Biomaterials 32:7411–7431, 2011.

    PubMed Central  CAS  PubMed  Google Scholar 

  69. Martins, R. P., J. D. Finan, F. Guilak, and D. A. Lee. Mechanical regulation of nuclear structure and function. Annu. Rev. Biomed. Eng. 14:431–455, 2012.

    PubMed Central  CAS  PubMed  Google Scholar 

  70. Masaeli, M., H. T. K. Tse, D. R. Gossett, D. Gupta, and D. Di Carlo. Multi-parameter High-Throughput Mechanic Phenotyping. Germany: Freiburg, pp. 383–385, 2013.

    Google Scholar 

  71. Mauck, R. L., B. M. Baker, N. L. Nerurkar, J. A. Burdick, W. J. Li, R. S. Tuan, et al. Engineering on the straight and narrow: the mechanics of nanofibrous assemblies for fiber-reinforced tissue regeneration. Tissue Eng. Part B Rev. 15:171–193, 2009.

    PubMed Central  CAS  PubMed  Google Scholar 

  72. McDevitt, C. A., and R. J. Webber. The ultrastructure and biochemistry of meniscal cartilage. Clin. Orthop. Relat. Res. 252:8–18, 1990.

    PubMed  Google Scholar 

  73. McNulty, A. L., J. B. Weinberg, and F. Guilak. Inhibition of matrix metalloproteinases enhances in vitro repair of the meniscus. Clin. Orthop. Relat. Res. 467:1557–1567, 2008.

  74. McNulty, A. L., B. T. Estes, R. E. Wilusz, J. B. Weinberg, and F. Guilak. Dynamic loading enhances integrative meniscal repair in the presence of interleukin-1. Osteoarthritis Cartilage 18:830–838, 2010.

    PubMed Central  CAS  PubMed  Google Scholar 

  75. McNulty, A. L., and F. Guilak. Integrative repair of the meniscus: lessons from in vitro studies. Biorheology 45:487–500, 2008.

    PubMed Central  PubMed  Google Scholar 

  76. McNulty, A. L., F. T. Moutos, J. B. Weinberg, and F. Guilak. Enhanced integrative repair of the porcine meniscus in vitro by inhibition of interleukin-1 or tumor necrosis factor alpha. Arthritis Rheum. 56:3033–3042, 2007.

    CAS  PubMed  Google Scholar 

  77. Meshorer, E., D. Yellajoshula, E. George, P. J. Scambler, D. T. Brown, and T. Misteli. Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev. Cell 10:105–116, 2006.

    PubMed Central  CAS  PubMed  Google Scholar 

  78. Mesiha, M., D. Zurakowski, J. Soriano, J. H. Nielson, B. Zarins, and M. M. Murray. Pathologic characteristics of the torn human meniscus. Am. J. Sports Med. 35:103–112, 2007.

    PubMed  Google Scholar 

  79. Metter, R. B., J. L. Ifkovits, K. Hou, L. Vincent, B. Hsu, L. Wang, et al. Biodegradable fibrous scaffolds with diverse properties by electrospinning candidates from a combinatorial macromer library. Acta Biomater. 6:1219–1226, 2010.

    PubMed Central  CAS  PubMed  Google Scholar 

  80. Moretti, M., D. Wendt, D. Schaefer, M. Jakob, E. B. Hunziker, M. Heberer, et al. Structural characterization and reliable biomechanical assessment of integrative cartilage repair. J. Biomech. 38:1846–1854, 2005.

    CAS  PubMed  Google Scholar 

  81. Namba, R. S., M. Meuli, K. M. Sullivan, A. X. Le, and N. S. Adzick. Spontaneous repair of superficial defects in articular cartilage in a fetal lamb model. J. Bone Joint Surg. Am. 80:4–10, 1998.

    CAS  PubMed  Google Scholar 

  82. Nathan, A. S., B. M. Baker, N. L. Nerurkar, and R. L. Mauck. Mechano-topographic modulation of stem cell nuclear shape on nanofibrous scaffolds. Acta Biomater. 7:57–66, 2010.

    PubMed Central  PubMed  Google Scholar 

  83. Natsu-Ume, T., T. Majima, C. Reno, N. G. Shrive, C. B. Frank, and D. A. Hart. Menisci of the rabbit knee require mechanical loading to maintain homeostasis: cyclic hydrostatic compression in vitro prevents derepression of catabolic genes. J. Orthop. Sci. 10:396–405, 2005.

    CAS  PubMed  Google Scholar 

  84. Nerurkar, N. L., B. M. Baker, S. Sen, E. E. Wible, D. M. Elliott, and R. L. Mauck. Nanofibrous biologic laminates replicate the form and function of the annulus fibrosus. Nat. Mater. 8:986–992, 2009.

    PubMed Central  CAS  PubMed  Google Scholar 

  85. Pajerowski, J. D., K. N. Dahl, F. L. Zhong, P. J. Sammak, and D. E. Discher. Physical plasticity of the nucleus in stem cell differentiation. Proc. Natl. Acad. Sci. USA 104:15619–15624, 2007.

    PubMed Central  CAS  PubMed  Google Scholar 

  86. Petersen, W., and B. Tillmann. Collagenous fibril texture of the human knee joint menisci. Anat. Embryol. (Berl). 197:317–324, 1998.

    CAS  PubMed  Google Scholar 

  87. Petrosini, A. V., and O. H. Sherman. A historical perspective on meniscal repair. Clin. Sports Med. 15:445–453, 1996.

    CAS  PubMed  Google Scholar 

  88. Peyton, S. R., and A. J. Putnam. Extracellular matrix rigidity governs smooth muscle cell motility in a biphasic fashion. J. Cell. Physiol. 204:198–209, 2005.

    CAS  PubMed  Google Scholar 

  89. Proctor, C. S., M. B. Schmidt, R. R. Whipple, M. A. Kelly, and V. C. Mow. Material properties of the normal medial bovine meniscus. J. Orthop. Res. 7:771–782, 1989.

    CAS  PubMed  Google Scholar 

  90. Provenzano, P. P., K. Hayashi, D. N. Kunz, M. D. Markel, and R. Vanderby, Jr. Healing of subfailure ligament injury: comparison between immature and mature ligaments in a rat model. J. Orthop. Res. 20:975–983, 2002.

    PubMed  Google Scholar 

  91. Purcell, B. P., D. Lobb, F. G. Spinale, and J. A. Burdick. On-demand delivery of TIMP-3 from injectable and MMP degradable hydrogels for infarct repair. In: Transaction of the 38th Annual Meeting: Pioneering the Future of Biomaterials, Vol. 38. Society for Biomaterials, p. 63, 2014.

  92. Purcell, B. P., J. A. Elser, A. Mu, K. B. Margulies, and J. A. Burdick. Synergistic effects of SDF-1alpha chemokine and hyaluronic acid release from degradable hydrogels on directing bone marrow derived cell homing to the myocardium. Biomaterials 33:7849–7857, 2012.

    PubMed Central  CAS  PubMed  Google Scholar 

  93. Purcell, B. P., D. Lobb, M. B. Charati, S. M. Dorsey, R. J. Wade, K. N. Zellars, et al. Injectable and bioresponsive hydrogels for on-demand matrix metalloproteinase inhibition. Nat. Mater. 13:653–661, 2014.

    PubMed Central  CAS  PubMed  Google Scholar 

  94. Purcell, B. P., D. Lobb, M. B. Charati, S. M. Dorsey, R. J. Wade, K. H. Zellars, et al. Injectable and bioresponsive hydrogels for on-demand matrix metalloproteinase inhibition. Nat. Mater. 13:653–661, 2014.

    PubMed Central  CAS  PubMed  Google Scholar 

  95. Qu, F., M.B. Fisher, and R. L. Mauck. The basic science of meniscus repair: endogenous limitations and emerging regenerative strategies, Chap. 10. In: Meniscal Surgery: Management and Techniques, edited by J. D. Kelly. Springer Science + Business Media, LLC, 2014, pp. 89–104.

  96. Qu, F., J. M. Lin, J. L. Esterhai, M. B. Fisher, and R. L. Mauck. Biomaterial-mediated delivery of degradative enzymes to improve meniscus integration and repair. Acta Biomater. 9:6393–6402, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  97. Qu, F., M. P. Pintauro, J. E. Haughan, E. A. Henning, J. L. Esterhai, T. P. Schaer, et al. Repair of dense connective tissues via biomaterial-mediated matrix reprogramming of the wound interface. Biomaterials 39:85–94, 2015.

    CAS  PubMed  Google Scholar 

  98. Rath, E., and J. C. Richmond. The menisci: basic science and advances in treatment. Br. J. Sports Med. 34:252–257, 2000.

    PubMed Central  CAS  PubMed  Google Scholar 

  99. Rowat, A. C., D. E. Jaalouk, M. Zwerger, W. L. Ung, I. A. Eydelnant, D. E. Olins, et al. Nuclear envelope composition determines the ability of neutrophil-type cells to passage through micron-scale constrictions. J. Biol. Chem. 288:8610–8618, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  100. Rowat, A. C., J. Lammerding, H. Herrmann, and U. Aebi. Towards an integrated understanding of the structure and mechanics of the cell nucleus. BioEssays 30:226–236, 2008.

    PubMed  Google Scholar 

  101. Scanzello, C. R., A. S. Albert, E. DiCarlo, K. B. Rajan, V. Kanda, E. U. Asomugha, et al. The influence of synovial inflammation and hyperplasia on symptomatic outcomes up to 2 years post-operatively in patients undergoing partial meniscectomy. Osteoarthritis Cartilage 21:1392–1399, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  102. Scanzello, C. R., and S. R. Goldring. The role of synovitis in osteoarthritis pathogenesis. Bone 51:249–257, 2012.

    PubMed Central  CAS  PubMed  Google Scholar 

  103. Scanzello, C. R., B. McKeon, B. H. Swaim, E. DiCarlo, E. U. Asomugha, V. Kanda, et al. Synovial inflammation in patients undergoing arthroscopic meniscectomy: molecular characterization and relationship to symptoms. Arthritis Rheum. 63:391–400, 2011.

    PubMed Central  PubMed  Google Scholar 

  104. Schmidt, S., and P. Friedl. Interstitial cell migration: integrin-dependent and alternative adhesion mechanisms. Cell Tissue Res. 339:83–92, 2010.

    PubMed Central  CAS  PubMed  Google Scholar 

  105. Shen, W., J. Chen, T. Zhu, L. Chen, W. Zhang, Z. Fang, et al. Intra-articular injection of human meniscus stem/progenitor cells promotes meniscus regeneration and ameliorates osteoarthritis through stromal cell-derived factor-1/CXCR4-mediated homing. Stem Cells Transl. Med. 3:387–394, 2014.

    PubMed Central  CAS  PubMed  Google Scholar 

  106. Shrive, N. G., J. J. O’Connor, and J. W. Goodfellow. Load-bearing in the knee joint. Clin. Orthop. 131:279–287, 1978.

    PubMed  Google Scholar 

  107. Sihvonen, R., M. Paavola, A. Malmivaara, A. Itala, A. Joukainen, H. Nurmi, et al. Arthroscopic partial meniscectomy versus sham surgery for a degenerative meniscal tear. N. Engl. J. Med. 369:2515–2524, 2013.

    CAS  PubMed  Google Scholar 

  108. Spivakov, M., and A. G. Fisher. Epigenetic signatures of stem-cell identity. Nat. Rev. Genet. 8:263–271, 2007.

    CAS  PubMed  Google Scholar 

  109. Struglics, A., M. Hansson, and L. S. Lohmander. Human aggrecanase generated synovial fluid fragment levels are elevated directly after knee injuries due to proteolysis both in the inter globular and chondroitin sulfate domains. Osteoarthritis Cartilage 19:1047–1057, 2011.

    CAS  PubMed  Google Scholar 

  110. Struglics, A., S. Larsson, M. A. Pratta, S. Kumar, M. W. Lark, and L. S. Lohmander. Human osteoarthritis synovial fluid and joint cartilage contain both aggrecanase- and matrix metalloproteinase-generated aggrecan fragments. Osteoarthritis Cartilage 14:101–113, 2006.

    CAS  PubMed  Google Scholar 

  111. Swift, J., I. L. Ivanovska, A. Buxboim, T. Harada, P. C. Dingal, J. Pinter, et al. Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science 341:1240104, 2013.

    PubMed Central  PubMed  Google Scholar 

  112. Talwar, S., A. Kumar, M. Rao, G. I. Menon, and G. V. Shivashankar. Correlated spatio-temporal fluctuations in chromatin compaction states characterize stem cells. Biophys. J . 104:553–564, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  113. Tchetverikov, I., L. S. Lohmander, N. Verzijl, T. W. Huizinga, J. M. TeKoppele, R. Hanemaaijer, et al. MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis. Ann. Rheum. Dis. 64:694–698, 2005.

    PubMed Central  CAS  PubMed  Google Scholar 

  114. Tenuta, J. J., and R. A. Arciero. Arthroscopic evaluation of meniscal repairs. Factors that effect healing. Am. J. Sports Med. 22:797–802, 1994.

    CAS  PubMed  Google Scholar 

  115. Upton, M. L., J. Chen, F. Guilak, and L. A. Setton. Differential effects of static and dynamic compression on meniscal cell gene expression. J. Orthop. Res. 21:963–969, 2003.

    CAS  PubMed  Google Scholar 

  116. Upton, M. L., A. Hennerbichler, B. Fermor, F. Guilak, J. B. Weinberg, and L. A. Setton. Biaxial strain effects on cells from the inner and outer regions of the meniscus. Connect. Tissue Res. 47:207–214, 2006.

    PubMed  Google Scholar 

  117. van de Breevaart Bravenboer, J., C. D. In der Maur, P. K. Bos, L. Feenstra, J. A. Verhaar, H. Weinans, et al. Improved cartilage integration and interfacial strength after enzymatic treatment in a cartilage transplantation model. Arthritis Res. Ther. 6:R469–R476, 2004.

    PubMed Central  PubMed  Google Scholar 

  118. Vanderhave, K. L., J. E. Moravek, J. K. Sekiya, and E. M. Wojtys. Meniscus tears in the young athlete: results of arthroscopic repair. J. Pediatr. Orthop. 31:496–500, 2011.

    PubMed  Google Scholar 

  119. Wade, R. J., and J. A. Burdick. Engineering ECM signals into biomaterials. Mater. Today 15:454–459, 2012.

    CAS  Google Scholar 

  120. Wojakowski, W., M. Tendera, A. Michalowska, M. Majka, M. Kucia, K. Maslankiewicz, et al. Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circulation 110:3213–3220, 2004.

    CAS  PubMed  Google Scholar 

  121. Wolf, K., and P. Friedl. Extracellular matrix determinants of proteolytic and non-proteolytic cell migration. Trends Cell Biol. 21:736–744, 2011.

    CAS  PubMed  Google Scholar 

  122. Wolf, K., M. Te Lindert, M. Krause, S. Alexander, J. Te Riet, A. L. Willis, et al. Physical limits of cell migration: control by ECM space and nuclear deformation and tuning by proteolysis and traction force. J. Cell Biol. 201:1069–1084, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  123. Zaman, M. H., L. M. Trapani, A. L. Sieminski, D. Mackellar, H. Gong, R. D. Kamm, et al. Migration of tumor cells in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis. Proc. Natl. Acad. Sci. USA 103:10889–10894, 2006.

    PubMed Central  CAS  PubMed  Google Scholar 

  124. Zwerger, M., D. E. Jaalouk, M. L. Lombardi, P. Isermann, M. Mauermann, G. Dialynas, et al. Myopathic lamin mutations impair nuclear stability in cells and tissue and disrupt nucleo-cytoskeletal coupling. Hum. Mol. Genet. 22:2335–2349, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported with grants from the National Institutes of Health (R01 EB008722 and AR056624) and the Department of Veterans Affairs (I01 RX000700 and RX000174). The authors gratefully acknowledge Dr. Brendon Baker, Dr. Matt Fisher, Dr. Lara Ionescu, Dr. Iris Kim, Dr. Brendan Purcell, and Ms. Feini (Sylvia) Qu for their helpful input, graphical design, and in depth discussions on this topic.

Conflict of interest

The authors have no conflicts of interest to report with respect to the submitted manuscript.

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  1. McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, 424 Stemmler Hall, 36th Street and Hamilton Walk, Philadelphia, PA, 19104, USA

    Robert L. Mauck

  2. Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 W. 33rd Street, Philadelphia, PA, 19104, USA

    Jason A. Burdick

  3. Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, 19104, USA

    Robert L. Mauck & Jason A. Burdick

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  1. Robert L. Mauck
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Correspondence to Robert L. Mauck or Jason A. Burdick.

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Associate Editor Nadya Lumelsky oversaw the review of this article.

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Mauck, R.L., Burdick, J.A. From Repair to Regeneration: Biomaterials to Reprogram the Meniscus Wound Microenvironment. Ann Biomed Eng 43, 529–542 (2015). https://doi.org/10.1007/s10439-015-1249-z

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