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Composites and Structures for Regenerative Engineering

  • Cato T. Laurencin (a1) (a2) (a3) (a4) and Roshan James (a1) (a2) (a4)

Abstract

Regenerative engineering was conceptualized by bridging the lessons learned in developmental biology and stem cell science with biomaterial constructs and engineering principles to ultimately generate de novo tissue. We seek to incorporate our understanding of natural tissue development to design tissue-inducing biomaterials, structures and composites than can stimulate the regeneration of complex tissues, organs, and organ systems through location-specific topographies and physico-chemical cues incorporated into a continuous phase. This combination of classical top-down tissue engineering approach with bottom-up strategies used in regenerative biology represents a new multidisciplinary paradigm. Advanced surface topographies and material scales are used to control cell fate and the consequent regenerative capacity.

Musculoskeletal tissues are critical to the normal functioning of an individual and following damage or degeneration they show extremely limited endogenous regenerative capacity. The increasing demand for biologically compatible donor tissue and organ transplants far outstrips the availability leading to an acute shortage. We have developed several biomimetic structures using various biomaterial platforms to combine optimal mechanical properties, porosity, bioactivity, and functionality to effect repair and regeneration of hard tissues such as bone, and soft tissues such as ligament and tendon. Starting with simple structures, we have developed composite and multi-scale systems that very closely mimic the native tissue architecture and material composition. Ultimately, we aim to modulate the regenerative potential, including proliferation, phenotype maturation, matrix production, and apoptosis through cell-scaffold and host –scaffold interactions developing complex tissues and organ systems.

Copyright

Corresponding author

* Corresponding author: Cato T. Laurencin, M.D.,Ph.D. University Professor University of Connecticut Health Center 263 Farmington Avenue, Farmington, CT, USA 06030 Phone: +1-860-679-6544 Fax: +1-860-679-1553 Email: laurencin@uchc.edu

References

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[1] Vacanti, J. P., “Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation,” Lancet, vol. 354, p. S32, 1999.
[2] Fung, Y., “A proposal to the National science Foundation for An Engineering Research Centre at USCD,” Center for the Engineering of Living Tissues. UCSD, vol. 865023, 2001.
[3] Bauer, T. W. and Muschler, G. F., “Bone graft materials: an overview of the basic science,” Clinical orthopaedics and related research, vol. 371, p. 10, 2000.
[4] Langer, R. and Vacanti, J., “Tissue engineering,” Science, vol. 260, pp. 920-926, May 14, 1993 1993.
[5] Laurencin, C. T. and Khan, Y., “Regenerative Engineering,” Science Translational Medicine, vol. 4, p. 160ed9, November 14, 2012 2012.
[6] 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.
[7] 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.
[8] Sharp, P. A. and Langer, R., “Promoting Convergence in Biomedical Science,” Science, vol. 333, p. 527, July 29, 2011 2011.
[9] Peerani, R., Rao, B. M., Bauwens, C., Yin, T., Wood, G. A., Nagy, A., et al. ., “Niche-mediated control of human embryonic stem cell self-renewal and differentiation,” EMBO J, vol. 26, pp. 4744–55, Nov 14 2007.
[10] Petersen, T. H., Calle, E. A., Zhao, L., Lee, E. J., Gui, L., Raredon, M. B., et al. ., “Tissue-Engineered Lungs for in Vivo Implantation,” Science, vol. 329, pp. 538-541, July 30, 2010 2010.
[11] Ott, H. C., Matthiesen, T. S., Goh, S.-K., Black, L. D., Kren, S. M., Netoff, T. I., et al. ., “Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart,” Nature medicine, vol. 14, pp. 213221, 2008.
[12] Badylak, S. F., Taylor, D., and Uygun, K., “Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds,” Annu Rev Biomed Eng, vol. 13, pp. 2753, Aug 15 2011.
[13] Dvir, T., Timko, B. P., Kohane, D. S., and Langer, R., “Nanotechnological strategies for engineering complex tissues,” Nat Nanotechnol, vol. 6, pp. 1322, Jan 2011.
[14] Kelleher, C. M. and Vacanti, J. P., “Engineering extracellular matrix through nanotechnology,” J R Soc Interface, vol. 7 Suppl 6, pp. S717–29, Dec 6 2010.
[15] James, R., Kesturu, G., Balian, G., and Chhabra, A. B., “Tendon: Biology, biomechanics, repair, growth factors, and evolving treatment options,” Journal of Hand Surgery-American Volume, vol. 33A, pp. 102112, Jan 2008.
[16] James, R., Deng, M., Laurencin, C., and Kumbar, S., “Nanocomposites and bone regeneration,” Frontiers of Materials Science, vol. 5, pp. 342357, 2011.
[17] Hogan, M. V., Bagayoko, N., James, R., Starnes, T., Katz, A., and Chhabra, A. B., “Tissue engineering solutions for tendon repair,” J Am Acad Orthop Surg, vol. 19, pp. 134–42, Mar 2011.
[18] Meng, D., James, R., Laurencin, C. T., and Kumbar, S. G., “Nanostructured Polymeric Scaffolds for Orthopaedic Regenerative Engineering,” NanoBioscience, IEEE Transactions on, vol. 11, pp. 314, 2012.
[19] Borden, M., Attawia, M., Khan, Y., and Laurencin, C. T., “Tissue engineered microsphere-based matrices for bone repair::: design and evaluation,” Biomaterials, vol. 23, pp. 551559, 2002.
[20] Borden, M., El-Amin, S., Attawia, M., and Laurencin, C., “Structural and human cellular assessment of a novel microsphere-based tissue engineered scaffold for bone repair,” Biomaterials, vol. 24, pp. 597609, 2003.
[21] Laurencin, C., Attawia, M., Lu, L., Borden, M., Lu, H., Gorum, W., et al. ., “Poly (lactide-co-glycolide)/hydroxyapatite delivery of BMP-2-producing cells: a regional gene therapy approach to bone regeneration,” Biomaterials, vol. 22, pp. 12711277, 2001.
[22] Roveri, N., Falini, G., Sidoti, M., Tampieri, A., Landi, E., Sandri, M., et al. ., “Biologically inspired growth of hydroxyapatite nanocrystals inside self-assembled collagen fibers,” Materials Science and Engineering: C, vol. 23, pp. 441446, 2003.
[23] Webster, T. J., Ergun, C., Doremus, R. H., Siegel, R. W., and Bizios, R., “Enhanced functions of osteoblasts on nanophase ceramics,” Biomaterials, vol. 21, pp. 18031810, 2000.
[24] Webster, T. J., Ergun, C., Doremus, R. H., Siegel, R. W., and Bizios, R., “Enhanced osteoclast-like cell functions on nanophase ceramics,” Biomaterials, vol. 22, pp. 13271333, 2001.
[25] Webster, T. J., Siegel, R. W., and Bizios, R., “Osteoblast adhesion on nanophase ceramics,” Biomaterials, vol. 20, pp. 12211227, 1999.
[26] Lv, Q., Nair, L., and Laurencin, C. T., “Fabrication, characterization, and in vitro evaluation of poly(lactic acid glycolic acid)/nano-hydroxyapatite composite microsphere-based scaffolds for bone tissue engineering in rotating bioreactors,” Journal of Biomedical Materials Research Part A, vol. 91A, pp. 679691, 2009.
[27] Kumbar, S. G., James, R., Nukavarapu, S. P., and Laurencin, C. T., “Electrospun nanofiber scaffolds: engineering soft tissues,” Biomedical materials, vol. 3, p. 034002, Sep 2008.
[28] Kumbar, S. G., Kofron, M. D., Nair, L. S., and Laurencin, C. T., “Cell Behavior Toward Nanostructured Surfaces,” in Biomedical Nanostructures, Gonsalves KE, H. C., Laurencin, CT, Nair LS, Ed., ed Hoboken, NJ, USA: John Wiley & Sons, 2007, pp. 261295.
[29] Li, W. J., Laurencin, C. T., Caterson, E. J., Tuan, R. S., and Ko, F. K., “Electrospun nanofibrous structure: a novel scaffold for tissue engineering,” J Biomed Mater Res, vol. 60, pp. 613–21, Jun 15 2002.
[30] Nair, L. S., Bhattacharyya, S., Bender, J. D., Greish, Y. E., Brown, P. W., Allcock, H. R., et al. ., “Fabrication and optimization of methylphenoxy substituted polyphosphazene nanofibers for biomedical applications,” Biomacromolecules, vol. 5, pp. 2212–20, 2004.
[31] Bhattacharyya, S., Nair, L. S., Singh, A., Krogman, N. R., Greish, Y. E., Brown, P. W., et al. ., “Electrospinning of poly[bis(ethyl alanato) phosphazene] nanofibersJ Biomed Nanotechnol, vol. 2, pp. 3645, 2006.
[32] Bhattacharyya, S., Kumbar, S. G., Khan, Y. M., Nair, L. S., Singh, A., Krogman, N. R., et al. ., “Biodegradable polyphosphazene-nanohydroxyapatite composite nanofibers: scaffolds for bone tissue engineering,” J Biomed Nanotechnol, vol. 5, pp. 6975, 2009.
[33] Li, W. J., Laurencin, C. T., Caterson, E. J., Tuan, R. S., and Ko, F. K., “Electrospun nanofibrous structure: A novel scaffold for tissue engineering,” Journal of Biomedical Materials Research, vol. 60, pp. 613621, Jun 2002.
[34] Christenson, E. M., Anseth, K. S., van den Beucken, J. J., Chan, C. K., Ercan, B., Jansen, J. A., et al. ., “Nanobiomaterial applications in orthopedics,” J Orthop Res, vol. 25, pp. 1122, 2007.
[35] Nair, L. S. and Laurencin, C. T., “Nanofibers and nanoparticles for orthopaedic surgery applications,” J Bone Joint Surg Am, vol. 90, pp. 128131, 2008.
[36] Nair, L. S., Bhattacharyya, S., and Laurencin, C. T., “Development of novel tissue engineering scaffolds via electrospinning,” Expert Opin Biol Ther, vol. 4, pp. 659668, 2004.
[37] Woo, K. M., Chen, V. J., and Ma, P. X., “Nano-fibrous scaffolding architecture selectively enhances protein adsorption contributing to cell attachment,” J Biomed Mater Res A, vol. 67A, pp. 531537, 2003.
[38] Pelled, G., Tai, K., Sheyn, D., Zilberman, Y., Kumbar, S., Nair, L. S., et al. ., “Structural and nanoindentation studies of stem cell-based tissue-engineered bone,” J Biomech, vol. 40, pp. 399411, 2007.
[39] Conconi, M. T., Lora, S., Menti, A. M., Carampin, P., and Parnigotto, P. P., “In vitro evaluation of poly[bis(ethyl alanato)phosphazene] as a scaffold for bone tissue engineering,” Tissue Eng, vol. 12, pp. 811–9, Apr 2006.
[40] Deng, M., Kumbar, S. G., Nair, L. S., Weikel, A. L., Allcock, H. R., and Laurencin, C. T., “Biomimetic structures: biological implications of dipeptide-substituted polyphosphazene-polyester blend nanofiber matrices for load-bearing bone regenerationAdv Funct Mater, vol. 21, pp. 26412651, 2011.
[41] Cooper, J. A. Jr., Sahota, J. S., Gorum, W. J. II, Carter, J., Doty, S. B., and Laurencin, C. T., “Biomimetic tissue-engineered anterior cruciate ligament replacement,” Proc Natl Acad Sci U S A, vol. 104, pp. 30493054, 2007.
[42] Peach, M. S., Roshan, J., Udaya, S. T., Meng, D., Nicole, L. M., Harry, R. A., et al. ., “Polyphosphazene functionalized polyester fiber matrices for tendon tissue engineering: in vitro evaluation with human mesenchymal stem cells,” Biomedical materials, vol. 7, p. 045016, 2012.
[43] Peach, M. S., Kumbar, S. G., James, R., Toti, U. S., Balasubramaniam, D., Deng, M., et al. ., “Design and optimization of polyphosphazene functionalized fiber matrices for soft tissue regeneration,” J Biomed Nanotechnol, vol. 8, pp. 107–24, 2012.
[44] James, R., Toti, U. S., Laurencin, C. T., and Kumbar, S. G., “Electrospun Nanofibrous Scaffolds for Engineering Soft Connective Tissues,” Methods Mol Biol, vol. 726, pp. 243258, 2011.

Keywords

Composites and Structures for Regenerative Engineering

  • Cato T. Laurencin (a1) (a2) (a3) (a4) and Roshan James (a1) (a2) (a4)

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