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Regenerative Engineering: Studies of the Rotator Cuff and other Musculoskeletal Soft Tissues

Published online by Cambridge University Press:  28 April 2016

Roshan James
Affiliation:
The Raymond and Beverly Sackler Center for Biomedical, Biological, Engineering and Physical Sciences, University of Connecticut Health Center, Farmington, CT 06030, U.S.A. Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT 06030, U.S.A. Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, U.S.A.
Paulos Mengsteab
Affiliation:
The Raymond and Beverly Sackler Center for Biomedical, Biological, Engineering and Physical Sciences, University of Connecticut Health Center, Farmington, CT 06030, U.S.A. Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT 06030, U.S.A. Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, U.S.A.
Cato T. Laurencin*
Affiliation:
The Raymond and Beverly Sackler Center for Biomedical, Biological, Engineering and Physical Sciences, University of Connecticut Health Center, Farmington, CT 06030, U.S.A. Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT 06030, U.S.A. Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, U.S.A. Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, U.S.A. Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, U.S.A. Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, U.S.A.
*
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Abstract

‘Regenerative Engineering’ is the integration of advanced materials science, stem cell science, physics, developmental biology and clinical translation to regenerate complex tissues and organ systems. Advanced biomaterial and stem cell science converge as mechanisms to guide regeneration and the development of prescribed cell lineages from undifferentiated stem cell populations. Studies in somite development and tissue specification have provided significant insight into pathways of biological regulation responsible for tissue determination, especially morphogen gradients, and paracrine and contact-dependent signaling. The understanding of developmental biology mechanisms are shifting the biomaterial design paradigm by the incorporation of molecules into scaffold design and biomaterial development that are specifically targeted to promote the regeneration of soft tissues. Our understanding allows the selective control of cell sensitivity, and a temporal and spatial arrangement to modulate the wound healing mechanism, and the development of cell phenotype leading to the patterning of distinct and multi-scale tissue systems.

Building on the development of mechanically compliant novel biomaterials, the integration of spatiotemporal control of biological, chemical and mechanical cues helps to modulate the stem cell niche and direct the differentiation of stem cell lineages. We have developed advanced biomaterials and biomimetic scaffold designs that can recapitulate the native tissue structure and mechanical compliance of soft musculoskeletal tissues, such as woven scaffold systems for ACL regeneration, non-woven scaffolds for rotator cuff tendon augmentation, and porous elastomers for regeneration of muscle tissue. Studies have clearly demonstrated the modulation of stem cell response to bulk biomaterial properties, such as toughness and elasticity, and scaffold structure, such as nanoscale and microscale dimensions. The integration of biological cues inspired from our understanding of developmental biology, along with chemical, mechanical and electrical stimulation drives our development of novel biomaterials aimed at specifying the stem cell lineage within 3-dimensional (3D) tissue systems. This talk will cover the development of biological cues, advanced biomaterials, and scaffold designs for the regeneration of complex soft musculoskeletal tissue systems such as ligament, tendon, and muscle.

Type
Articles
Copyright
Copyright © Materials Research Society 2016 

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References

REFERENCES

Langer, R. and Vacanti, J. P., “Tissue Engineering,” Science, vol. 260, pp. 920926, 1993.Google Scholar
James, R., Daley, G. Q., and Laurencin, C. T., “Regenerative Engineering: Materials, Mimicry, and Manipulations to Promote Cell and Tissue Growth,” National Academy of Engineering - The Bridge: The Convergence of Engineering and the Life Sciences; Editors: Philip A. Sharp and Robert Langer, vol. 43, p. 8, 2013.Google Scholar
Reichert, W., Ratner, B. D., Anderson, J., Coury, A., Hoffman, A. S., Laurencin, C. T., et al., “2010 Panel on the biomaterials grand challenges,” Journal of Biomedical Materials Research Part A, vol. 96, pp. 275287, 2011.Google Scholar
Lorda-Diez, C. I., Montero, J. A., Garcia-Porrero, J. A., and Hurle, J. M., “Divergent differentiation of skeletal progenitors into cartilage and tendon: lessons from the embryonic limb,” ACS chemical biology, vol. 9, pp. 7279, 2013.Google Scholar
Laurencin, C. T. and Khan, Y., Regenerative engineering: CRC Press, 2013.Google Scholar
Deng, M., James, R., Laurencin, C. T., and Kumbar, S. G., “Nanostructured polymeric scaffolds for orthopaedic regenerative engineering,” IEEE Trans Nanobioscience, vol. 11, pp. 314, Mar 2012.Google Scholar
Rayan, F., Nanjayan, S. K., Quah, C., Ramoutar, D., Konan, S., and Haddad, F. S., “Review of evolution of tunnel position in anterior cruciate ligament reconstruction,” World J Orthop, vol. 6, pp. 252–62, Mar 18 2015.CrossRefGoogle Scholar
Amiel, D., Frank, C., Harwood, F., Fronek, J., and Akeson, W., “Tendons and ligaments: a morphological and biochemical comparison,” Journal of orthopaedic research : official publication of the Orthopaedic Research Society, vol. 1, pp. 257265, 1984.CrossRefGoogle Scholar
Hoffmann, A. and Gross, G., “Tendon and ligament engineering: from cell biology to in vivo application,” Regen Med, vol. 1, pp. 563–74, Jul 2006.CrossRefGoogle Scholar
Frank, C. B. and Jackson, D. W., “Current Concepts Review-The Science of Reconstruction of the Anterior Cruciate Ligament*,” The Journal of Bone & Joint Surgery, vol. 79, pp. 1556–76, 1997.Google Scholar
Regeneration, S. T., “Announcement on the completion of patient enrollment in LC ligament European clinical trial,” ed, 2014.Google Scholar
Cooper, J. A., Sahota, J. S., Gorum, W. J., Carter, J., Doty, S. B., and Laurencin, C. T., “Biomimetic tissue-engineered anterior cruciate ligament replacement,” Proceedings of the National Academy of Sciences, vol. 104, p. 3049, 2007.Google Scholar
Cooper, J. A., Lu, H. H., Ko, F. K., Freeman, J. W., and Laurencin, C. T., “Fiber-based tissue-engineered scaffold for ligament replacement: design considerations and in vitro evaluation,” Biomaterials, vol. 26, pp. 15231532, May 2005.CrossRefGoogle Scholar
Cooper, J. A. Jr, Bailey, L. O., Carter, J. N., Castiglioni, C. E., Kofron, M. D., Ko, F. K., et al., “Evaluation of the anterior cruciate ligament, medial collateral ligament, achilles tendon and patellar tendon as cell sources for tissue-engineered ligament,” Biomaterials, vol. 27, pp. 27472754, 5// 2006.Google Scholar
Hogan, M., Girish, K., James, R., Balian, G., Hurwitz, S., and Chhabra, A. B., “Growth differentiation factor-5 regulation of extracellular matrix gene expression in murine tendon fibroblasts,” Journal of tissue engineering and regenerative medicine, vol. 5, pp. 191200, Mar 2011.Google Scholar
James, R., Kumbar, S. G., Laurencin, C. T., Balian, G., and Chhabra, A. B., “Tendon tissue engineering: adipose-derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems,” Biomedical materials, vol. 6, p. 025011, Apr 2011.Google Scholar
Mikic, B., Schalet, B. J., Clark, R. T., Gaschen, V., and Hunziker, E. B., “GDF-5 deficiency in mice alters the ultrastructure, mechanical properties and composition of the Achilles tendon,” Journal of Orthopaedic Research, vol. 19, pp. 365371, May 2001.Google Scholar
Storm, E. E. and Kingsley, D. M., “GDF5 coordinates bone and joint formation during digit development,” Developmental Biology, vol. 209, pp. 1127, May 1999.CrossRefGoogle Scholar
Brent, A. E. and Tabin, C. J., “FGF acts directly on the somitic tendon progenitors through the Ets transcription factors Pea3 and Erm to regulate scleraxis expression,” Development, vol. 131, pp. 3885–96, Aug 2004.Google Scholar
Tozer, S. and Duprez, D., “Tendon and ligament: development, repair and disease,” Birth Defects Research Part C: Embryo Today: Reviews, vol. 75, pp. 226236, 2005.Google Scholar
Park, A., Hogan, M. V., Kesturu, G. S., James, R., Balian, G., and Chhabra, A. B., “Adipose-derived mesenchymal stem cells treated with growth differentiation factor-5 express tendon-specific markers,” Tissue Eng Part A, vol. 16, pp. 2941–51, Sep 2010.Google Scholar
Brent, A. E., Schweitzer, R., and Tabin, C. J., “A somitic compartment of tendon progenitors,” Cell, vol. 113, pp. 235–48, Apr 18 2003.Google Scholar
Pryce, B. A., Watson, S. S., Murchison, N. D., Staverosky, J. A., Dünker, N., and Schweitzer, R., “Recruitment and maintenance of tendon progenitors by TGFβ signaling are essential for tendon formation,” Development, vol. 136, pp. 13511361, 2009.Google Scholar
Havis, E., Bonnin, M.-A., Olivera-Martinez, I., Nazaret, N., Ruggiu, M., Weibel, J., et al., “Transcriptomic analysis of mouse limb tendon cells during development,” Development, vol. 141, pp. 36833696, 2014.Google Scholar
Longo, U. G., Lamberti, A., Maffulli, N., and Denaro, V., “Tissue engineered biological augmentation for tendon healing: a systematic review,” British medical bulletin, Sep 17 2010.Google Scholar
Gerber, C., Fuchs, B., and Hodler, J., “The results of repair of massive tears of the rotator cuff,” J Bone Joint Surg Am, vol. 82, pp. 505–15, Apr 2000.Google Scholar
Goutallier, D., Postel, J. M., Bernageau, J., Lavau, L., and Voisin, M. C., “Fatty infiltration of disrupted rotator cuff muscles,” Rev Rhum Engl Ed, vol. 62, pp. 415–22, Jun 1995.Google Scholar
Kang, J. R. and Gupta, R., “Mechanisms of fatty degeneration in massive rotator cuff tears,” J Shoulder Elbow Surg, vol. 21, pp. 175–80, Feb 2012.Google Scholar
Maffulli, N. and John, M. D.Furia, P., Rotator Cuff Disorders: Basic Science & Clinical Medicine: Jp Medical Pub, 2012.Google Scholar
Nakagaki, K., Ozaki, J., Tomita, Y., and Tamai, S., “Fatty degeneration in the supraspinatus muscle after rotator cuff tear,” J Shoulder Elbow Surg, vol. 5, pp. 194200, May-Jun 1996.Google Scholar
Safran, O., Derwin, K. A., Powell, K., and Iannotti, J. P., “Changes in rotator cuff muscle volume, fat content, and passive mechanics after chronic detachment in a canine model,” J Bone Joint Surg Am, vol. 87, pp. 2662–70, Dec 2005.Google Scholar
Park, H. S., Gong, M. S., Park, J. H., Moon, S. I., Wall, I. B., Kim, H. W., et al., “Silk fibroin-polyurethane blends: physical properties and effect of silk fibroin content on viscoelasticity, biocompatibility and myoblast differentiation,” Acta Biomater, vol. 9, pp. 8962–71, Nov 2013.CrossRefGoogle Scholar
Xu, B., Li, Y., Fang, X., Thouas, G. A., Cook, W. D., Newgreen, D. F., et al., “Mechanically tissue-like elastomeric polymers and their potential as a vehicle to deliver functional cardiomyocytes,” J Mech Behav Biomed Mater, vol. 28, pp. 354–65, Dec 2013.Google Scholar