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22 - Endogenous stem/progenitor cell recruitment for tissue regeneration

from Part IV - Biological factor delivery

Published online by Cambridge University Press:  05 February 2015

By
Mildred Embree ,
Chang Hun Lee ,
Ziming Dong ,
Mo Chen ,
Kimi Kong ,
Hemin Nie ,
Avital Mendelson ,
Bhranti Shah ,
Shoko Cho  and
Takahiro Suzuki
...Show all authors
Edited by
Peter X. Ma
Mildred Embree
Affiliation:
Columbia University Medical Center
Chang Hun Lee
Affiliation:
Columbia University Medical Center
Ziming Dong
Affiliation:
Zhengzhou University
Mo Chen
Affiliation:
Columbia University Medical Center
Kimi Kong
Affiliation:
Columbia University Medical Center
Hemin Nie
Affiliation:
Columbia University Medical Center
Avital Mendelson
Affiliation:
Columbia University Medical Center
Bhranti Shah
Affiliation:
Columbia University Medical Center
Shoko Cho
Affiliation:
Columbia University Medical Center
Takahiro Suzuki
Affiliation:
Columbia University Medical Center
Rujing Yang
Affiliation:
Columbia University Medical Center
Nan Jiang
Affiliation:
Columbia University Medical Center
Jeremy J. Mao
Affiliation:
Columbia University Medical Center
Peter X. Ma
Affiliation:
University of Michigan, Ann Arbor
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Summary

Introduction: stem/progenitor cell recruitment vs. transplantation

The utilization of transplanted stem cells in regenerative medicine has been studied extensively as a potential therapy to repair or replace tissues that are lost due to trauma, congenital deformities, tumor resections, or infectious diseases [1–3]. The current cell transplantation model in regenerative medicine is founded on the principle that the application of transplanted stem cells could repopulate and regenerate damaged or diseased tissues, with restored tissue functions and homeostasis. However, cell transplantation is faced with a multitude of clinical and cell culture complications including the complexity of the multistep surgical procedures, donor-site trauma, immune rejection for allogeneic and xenogeneic cells, cell phenotypic variations due to in-vitro culture techniques, potential tumorigenesis associated with long-term cell expansion, failure of exogenous cell engraftment, and uncertainties and difficulties in the regulatory approval process [4–8]. The difficulties in the clinical application of stem cell transplantation are in strong contrast to the results of multiple experimental studies that demonstrate different levels of efficacy of cell delivery in a number of disease models such as Parkinson’s disease [9, 10], blood cancers and diseases [11, 12], and muscle and spinal disorders/injuries [13, 14].

For a number of regenerative medicine applications, the use of stem cell transplantation might not be competitive with the cost-effectiveness of current clinical treatment modalities in the dental and musculoskeletal fields, including titanium joint replacements, dental implants, and operative dental procedures [15–17]. Alternatively, the concept of endogenous stem/progenitor cell recruitment in regenerative medicine is based on the idea that native stem/progenitor cells that already reside within mature tissue can be stimulated and functionally enhanced to repopulate, repair, and/or regenerate damaged tissues [18]. Relative to stem cell transplantation, the application of endogenous stem cell recruitment in regenerative medicine is still in its infancy. The combination of the use of biological factors, release technology, biomaterials, and bioengineered scaffolds to enhance endogenous stem cell recruitment seems very promising for potential use in translational regenerative medicine. However, further scientific experimentation is warranted, since many scientific questions concerning the mechanistic details remain unresolved and it will be necessary to validate the efficacy of this approach for clinical application.

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Information
Biomaterials and Regenerative Medicine , pp. 405 - 418
Publisher: Cambridge University Press
Print publication year: 2014

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References

Passier, R., van Laake, L. W. and Mummery, C. L. 2008. Stem-cell-based therapy and lessons from the heart. Nature, 453(7193), 322–9.CrossRefGoogle ScholarPubMed
Lindvall, O. and Kokaia, Z. 2006. Stem cells for the treatment of neurological disorders. Nature, 441(7097), 1094–6.CrossRefGoogle ScholarPubMed
Rafii, S. and Lyden, D. 2003. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nature Med., 9(6), 702–12.CrossRefGoogle ScholarPubMed
Burt, R. K., Shah, S. J., Diu, K. et al. 2011. Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial. Lancet, 378(9790), 498–506.CrossRefGoogle ScholarPubMed
Bongso, A., Fong, C. Y. and Gauthaman, K. 2008. Taking stem cells to the clinic: major challenges. J. Cell Biochem., 105(6), 1352–60.CrossRefGoogle ScholarPubMed
Condic, M. L. and Rao, M. 2008. Regulatory issues for personalized pluripotent cells. Stem Cells, 26(11), 2753–8.CrossRefGoogle ScholarPubMed
Fujikawa, T., Oh, S. H., Pi, L. et al. 2005. Teratoma formation leads to failure of treatment for type I diabetes using embryonic stem cell-derived insulin-producing cells. Am. J. Pathol., 166(6), 1781–91.CrossRefGoogle ScholarPubMed
Nussbaum, J., Minami, E., Laflamme, M. A. et al. 2007. Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response. FASEB J., 21(7), 1345–57.CrossRefGoogle ScholarPubMed
Ben-Hur, T., Idelson, M., Khaner, H. et al. 2004. Transplantation of human embryonic stem cell-derived neural progenitors improves behavioral deficit in Parkinsonian rats. Stem Cells, 22(7), 1246–55.CrossRefGoogle ScholarPubMed
Yang, D., Zhang, Z.-J., Oldenburg, M., Ayala, M. and Zhang, S.-C. 2008. Human embryonic stem cell-derived dopaminergic neurons reverse functional deficit in Parkinsonian rats. Stem Cells, 26(1), 55–63.CrossRefGoogle ScholarPubMed
Andersson, B. S. 2010. Advances in CML: the role of allogeneic hematopoietic stem cell transplantation. Clin. Adv. Hematol. Oncol., 8(11), 746–8.Google ScholarPubMed
Dreger, P., Döhner, H., Ritgen, M. et al. 2010. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood, 116(14), 2438–47.CrossRefGoogle Scholar
Ferrari, G., Cusella-De Angelis, G., Coletta, M. et al. 1998. Muscle regeneration by bone marrow-derived myogenic progenitors. Science, 279(5356), 1528–30.CrossRefGoogle ScholarPubMed
Sahni, V. and Kessler, J. A. 2010. Stem cell therapies for spinal cord injury. Nature Rev. Neurol., 6(7), 363–72.CrossRefGoogle ScholarPubMed
Lindahl, A., Brittberg, M. and Peterson, L. 2003. Cartilage repair with chondrocytes: clinical and cellular aspects. Novartis Found. Symp., 249, p. 175–86; discussion 186–9, 234–8 and 239–41.Google ScholarPubMed
Iacono, V. J. 2000. Dental implants in periodontal therapy. J. Periodontol., 71(12), 1934–42.Google ScholarPubMed
Clar, C., Cummins, E., McIntyre, L. et al. 2005. Clinical and cost-effectiveness of autologous chondrocyte implantation for cartilage defects in knee joints: systematic review and economic evaluation. Health Technol. Assess., 9(47), iii–iv, ix–x, and 1–82.CrossRefGoogle ScholarPubMed
Chen, F. M., Wu, L. A., Zhang, M., Zhang, R. and Sun, H. H. 2011. Homing of endogenous stem/progenitor cells for in situ tissue regeneration: Promises, strategies, and translational perspectives. Biomaterials, 32(12), 3189–209.CrossRefGoogle ScholarPubMed
Grossman, Z. 1986. The stem cell concept revisited: self-renewal capacity is a dynamic property of hemopoietic cells. Leuk. Res., 10(8), 937–50.CrossRefGoogle ScholarPubMed
Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S. et al. 1998. Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145–7.CrossRefGoogle ScholarPubMed
Volarević, V., Ljujić, B., Stojković, P. et al. 2011. Human stem cell research and regenerative medicine – present and future. Br. Med. Bull., 99, 155–68.CrossRefGoogle ScholarPubMed
Takahashi, K. and Yamanaka, S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663–76.CrossRefGoogle ScholarPubMed
Yu, J., Hu, K., Smuga-Otto, K. et al. 2009. Human induced pluripotent stem cells free of vector and transgene sequences. Science, 324(5928), 797–801.CrossRefGoogle ScholarPubMed
Leong, K. G., Wang, B. E., Johnson, L. and Gao, W. Q. 2008. Generation of a prostate from a single adult stem cell. Nature, 456(7223), 804–8.CrossRefGoogle ScholarPubMed
Beltrami, A. P., Barlucchi, L., Torella, D. et al. 2003. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell, 114(6), 763–76.CrossRefGoogle ScholarPubMed
Mishra, R., Vijayan, K., Colletti, E. J. et al. 2011. Characterization and functionality of cardiac progenitor cells in congenital heart patients. Circulation, 123(4), 364–73.CrossRefGoogle ScholarPubMed
McKay, R. D. 1999. Brain stem cells change their identity. Nature Med., 5(3), 261–2.CrossRefGoogle ScholarPubMed
Liechty, K. W., MacKenzie, T. C., Shaaban, A. F. et al. 2000. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nature Med., 6(11), 1282–6.CrossRefGoogle Scholar
Gerson, S. L. 1999. Mesenchymal stem cells: no longer second class marrow citizens. Nature Med., 5(3), 262–4.CrossRefGoogle ScholarPubMed
Orkin, S. H. and Zon, L. I. 2008. Hematopoiesis: an evolving paradigm for stem cell biology. Cell, 132(4), 631–44.CrossRefGoogle ScholarPubMed
Huang, G. T., Gronthos, S. and Shi, S. 2009. Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J. Dent. Res., 88(9), 792–806.CrossRefGoogle ScholarPubMed
Bi, Y., Ehirchiou, D., Kilts, T. M. et al. 2007. Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nature Med., 13(10), 1219–27.CrossRefGoogle ScholarPubMed
Koelling, S., Kruegel, J., Irmer, M. et al. 2009. Migratory chondrogenic progenitor cells from repair tissue during the later stages of human osteoarthritis. Cell Stem Cell, 4(4), 324–35.CrossRefGoogle ScholarPubMed
Mitchell, K. J., Pannérec, A., Cadot, B. et al. 2010. Identification and characterization of a non-satellite cell muscle resident progenitor during postnatal development. Nature Cell Biol., 12(3), 257–66.Google ScholarPubMed
Blanpain, C., Lowry, W. E., Geoghegan, A. et al. 2004. Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell, 118(5), 635–48.CrossRefGoogle ScholarPubMed
Bongso, A. and Richards, M. 2004. History and perspective of stem cell research. Best Pract. Res. Clin. Obstet. Gynaecol., 18(6), 827–42.CrossRefGoogle ScholarPubMed
Encinas, J. M., Michurina, T. V., Peunova, N. et al. 2011. Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell, 8(5), 566–79.CrossRefGoogle ScholarPubMed
Scadden, D. T. 2006. The stem-cell niche as an entity of action. Nature, 441(7097), 1075–9.CrossRefGoogle Scholar
Voog, J. and Jones, D. L. 2010. Stem cells and the niche: a dynamic duo. Cell Stem Cell, 6(2), 103–15.CrossRefGoogle ScholarPubMed
Laird, D. J., von Andrian, U. H. and Wagers, A. J. 2008. Stem cell trafficking in tissue development, growth, and disease. Cell, 132(4), 612–30.CrossRefGoogle ScholarPubMed
Lapidot, T., Dar, A. and Kollet, O. 2005. How do stem cells find their way home? Blood, 106(6), 1901–10.CrossRefGoogle ScholarPubMed
Lapidot, T. and Kollet, O. 2002. The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD/SCID and NOD/SCID/B2m(null) mice. Leukemia, 16(10), 1992–2003.CrossRefGoogle ScholarPubMed
Ponomaryov, T., Peled, A., Petit, I. et al. 2000. Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function. J. Clin. Invest., 106(11), 1331–9.CrossRefGoogle ScholarPubMed
Imai, K., Kobayashi, M., Wang, J. et al. 1999. Selective secretion of chemoattractants for haemopoietic progenitor cells by bone marrow endothelial cells: a possible role in homing of haemopoietic progenitor cells to bone marrow. Br. J. Haematol., 106(4), 905–11.CrossRefGoogle ScholarPubMed
Loetscher, M., Geiser, T., O’Reilly, T. et al. 1994. Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J. Biol. Chem., 269(1), 232–7.Google Scholar
Kawabata, K., Ujikawa, M., Egawa, T. et al. 1999. A cell-autonomous requirement for CXCR4 in long-term lymphoid and myeloid reconstitution. Proc. Nat. Acad. Sci. USA, 96(10), 5663–7.CrossRefGoogle ScholarPubMed
Tachibana, K., Hirota, S., Iizasa, H. et al. 1998. The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature, 393(6685), 591–4.CrossRefGoogle ScholarPubMed
Ceradini, D. J., Kulkarni, A. R., Callaghan, M. J. et al. 2004. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nature Med., 10(8), 858–64.CrossRefGoogle ScholarPubMed
Avecilla, S. T., Hattori, K., Heissig, B. et al. 2004. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nature Med., 10(1), 64–71.CrossRefGoogle ScholarPubMed
Zaruba, M. M. and Franz, W. M. 2010. Role of the SDF-1–CXCR4 axis in stem cell-based therapies for ischemic cardiomyopathy. Expert Opin. Biol. Ther., 10(3), 321–35.CrossRefGoogle ScholarPubMed
Togel, F., Isaac, J., Hu, Z., Weiss, K. and Westenfelder, C. 2005. Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury. Kidney Int., 67(5), 1772–84.CrossRefGoogle ScholarPubMed
Ratanavaraporn, J., Furuya, H., Kohara, H. and Tabata, Y. 2011. Synergistic effects of the dual release of stromal cell-derived factor-1 and bone morphogenetic protein-2 from hydrogels on bone regeneration. Biomaterials, 32(11), 2797–811.CrossRefGoogle ScholarPubMed
Heissig, B., Hattori, K., Dias, S. et al. 2002. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell, 109(5), 625–37.CrossRefGoogle ScholarPubMed
Kollet, O., Dar, A., Shirtiel, S. et al. 2006. Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells. Nature Med., 12(6), 657–64.CrossRefGoogle ScholarPubMed
Pappu, R., Schwab, S. R., Cornelissen, I. et al. 2007. Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science, 316(5822), 295–8.CrossRefGoogle ScholarPubMed
Lévesque, J. P., Takamatsu, Y., Nilsson, S. K., Haylock, D. N. and Simmons, P. J. 2001. Vascular cell adhesion molecule-1 (CD106) is cleaved by neutrophil proteases in the bone marrow following hematopoietic progenitor cell mobilization by granulocyte colony-stimulating factor. Blood, 98(5), 1289–97.CrossRefGoogle ScholarPubMed
Papayannopoulou, T., Craddock, C., Nakamoto, B., Priestley, G. V. and Wolf, N. S. 1995. The VLA4/VCAM-1 adhesion pathway defines contrasting mechanisms of lodgement of transplanted murine hemopoietic progenitors between bone marrow and spleen. Proc. Nat. Acad. Sci. USA, 92(21), 9647–51.CrossRefGoogle ScholarPubMed
Kuznetsov, S. A., Mankani, M. H., Gronthos, S. et al. 2001. Circulating skeletal stem cells. J. Cell. Biol., 153(5), 1133–40.CrossRefGoogle ScholarPubMed
Mauney, J., Olsen, B. R. and Volloch, V. 2010. Matrix remodeling as stem cell recruitment event: a novel in vitro model for homing of human bone marrow stromal cells to the site of injury shows crucial role of extracellular collagen matrix. Matrix Biol., 29(8), 657–63.CrossRefGoogle ScholarPubMed
Wang, J. A., He, A., Hu, X. et al. 2009. Anoxic preconditioning: a way to enhance the cardioprotection of mesenchymal stem cells. Int. J. Cardiol., 133(3), 410–12.CrossRefGoogle ScholarPubMed
Karp, J. M. and Leng Teo, G. S. 2009. Mesenchymal stem cell homing: the devil is in the details. Cell Stem Cell, 4(3), 206–16.CrossRefGoogle ScholarPubMed
Lee, P. H., Kim, J. W., Bang, O. Y. et al. 2008. Autologous mesenchymal stem cell therapy delays the progression of neurological deficits in patients with multiple system atrophy. Clin. Pharmacol. Ther., 83(5), 723–30.CrossRefGoogle ScholarPubMed
Sackstein, R., Merzaban, J. S., Cain, D. W. et al. 2008. Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone. Nature Med., 14(2), 181–7.CrossRefGoogle ScholarPubMed
Lee, K., Silva, E. A. and Mooney, D. J. 2011. Growth factor delivery-based tissue engineering: general approaches and a review of recent developments. J. R. Soc. Interface, 8(55), 153–70.CrossRefGoogle Scholar
Moioli, E. K., Clark, P. A., Xin, X., Lal, S. and Mao, J. J. 2007. Matrices and scaffolds for drug delivery in dental, oral and craniofacial tissue engineering. Adv. Drug Deliv. Rev., 59(4–5), 308–24.CrossRefGoogle ScholarPubMed
Moioli, E. K. and Mao, J. J. 2006. Chondrogenesis of mesenchymal stem cells by controlled delivery of transforming growth factor-β3. In Conference Proceedings of the IEEE Engineering in Medicine and Biology Society, pp. 2647–50.
Lee, C. H., Cock, J. L., Mendelson, A. et al. 2010. Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study. Lancet, 376(9739), 440–8.CrossRefGoogle ScholarPubMed
Mendelson, A., Frank, E., Allred, C. et al. 2011. Chondrogenesis by chemotactic homing of synovium, bone marrow, and adipose stem cells in vitro. FASEB J., 25(10), 3496–504.CrossRefGoogle ScholarPubMed
Chen, F. M., Zhang, M. and Wu, Z. F. 2010. Toward delivery of multiple growth factors in tissue engineering. Biomaterials, 31(24), 6279–308.CrossRefGoogle ScholarPubMed
Kimura, Y., Miyazaki, N., Hayashi, N. et al. 2010. Controlled release of bone morphogenetic protein-2 enhances recruitment of osteogenic progenitor cells for de novo generation of bone tissue. Tissue Eng. Part A, 16(4), 1263–70.CrossRefGoogle Scholar
Chen, F. M., Shelton, R. M., Jin, Y. and Chapple, I. L. 2009. Localized delivery of growth factors for periodontal tissue regeneration: role, strategies, and perspectives. Med. Res. Rev., 29(3), 472–513.CrossRefGoogle Scholar
Vasita, R. and Katti, D. S. 2006. Growth factor-delivery systems for tissue engineering: a materials perspective. Expert Rev. Med. Devices, 3(1), 29–47.CrossRefGoogle ScholarPubMed
Zhang, S. and Uludag, H. 2009. Nanoparticulate systems for growth factor delivery. Pharm. Res., 26(7), 1561–80.CrossRefGoogle ScholarPubMed
Uebersax, L., Merkle, H. P. and Meinel, L. 2009. Biopolymer-based growth factor delivery for tissue repair: from natural concepts to engineered systems. Tissue Eng. Part B Rev., 15(3), 263–89.CrossRefGoogle ScholarPubMed
Robinson, R., Viviano, S. R., Criscione, J. M. et al. 2011. Nanospheres delivering the EGFR TKI AG1478 promote optic nerve regeneration: the role of size for intraocular drug delivery. ACS Nano, 5(6), 4392–400.CrossRefGoogle ScholarPubMed
Askari, A. T., Unzek, S., Popovic, Z. B. et al. 2003. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet, 362(9385), 697–703.CrossRefGoogle ScholarPubMed
Guldberg, R. E. 2009. Spatiotemporal delivery strategies for promoting musculoskeletal tissue regeneration. J. Bone Miner. Res., 24(9), 1507–11.CrossRefGoogle ScholarPubMed
Riley, C. M., Fuegy, P. W., Firpo, M. A. et al. 2006. Stimulation of in vivo angiogenesis using dual growth factor-loaded crosslinked glycosaminoglycan hydrogels. Biomaterials, 27(35), 5935–43.CrossRefGoogle ScholarPubMed
Ulery, B. D., Nair, L. S. and Laurencin, C. T. 2011. Biomedical applications of biodegradable polymers. J. Polym. Sci. B Polym. Phys., 49(12), 832–64.CrossRefGoogle ScholarPubMed
Place, E. S., George, J. H., Williams, C. K. and Stevens, M. M. 2009. Synthetic polymer scaffolds for tissue engineering. Chem. Soc. Rev., 38(4), 1139–51.CrossRefGoogle ScholarPubMed
Sokolsky-Papkov, M., Agashi, K., Olaye, A., Shakesheff, K. and Domb, A. J. 2007. Polymer carriers for drug delivery in tissue engineering. Adv. Drug Deliv. Rev., 59(4–5), 187–206.CrossRefGoogle ScholarPubMed
Godier-Furnémont, A. F., Marten, T. P., Koeckert, M. S. et al. 2011. Composite scaffold provides a cell delivery platform for cardiovascular repair. Proc. Nat. Acad. Sci. USA, 108(19), 7974–9.CrossRefGoogle ScholarPubMed
Briganti, E., Spiller, D., Mirtelli, C. et al. 2010. A composite fibrin-based scaffold for controlled delivery of bioactive pro-angiogenetic growth factors. J. Control. Release, 142(1), 14–21.CrossRefGoogle ScholarPubMed
Zhu, X. H., Wang, C. H. and Tong, Y. W. 2009. In vitro characterization of hepatocyte growth factor release from PHBV/PLGA microsphere scaffold. J. Biomed. Mater. Res. A, 89(2), 411–23.CrossRefGoogle ScholarPubMed
Panyam, J. and Labhasetwar, V. 2003. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv. Drug Deliv. Rev., 55(3), 329–47.CrossRefGoogle Scholar
Lee, K. Y. and Mooney, D. J. 2001. Hydrogels for tissue engineering. Chem. Rev., 101(7), 1869–79.CrossRefGoogle ScholarPubMed
Santo, V. E., Frias, A. M., Carida, M. et al. 2009. Carrageenan-based hydrogels for the controlled delivery of PDGF-BB in bone tissue engineering applications. Biomacromolecules, 10(6), 1392–401.CrossRefGoogle ScholarPubMed
Zisch, A. H., Lutolf, M. P., Ehrbar, M. et al. 2003. Cell-demanded release of VEGF from synthetic, biointeractive cell ingrowth matrices for vascularized tissue growth. FASEB J., 17(15), 2260–2.CrossRefGoogle ScholarPubMed
Siepmann, F., Siepmann, J., Walther, M., MacRae, R. J. and Bodmeier, R. 2008. Polymer blends for controlled release coatings. J. Control. Release, 125(1), 1–15.CrossRefGoogle ScholarPubMed
Srouji, S., Ben-David, D., Lotan, R. et al. 2011. Slow-release human recombinant bone morphogenetic protein-2 embedded within electrospun scaffolds for regeneration of bone defect: in vitro and in vivo evaluation. Tissue Eng. Part A, 17(3–4), 269–77.CrossRefGoogle ScholarPubMed
Liao, I. C., Chew, S. Y. and Leong, K. W. 2006. Aligned core–shell nanofibers delivering bioactive proteins. Nanomedicine (Lond.), 1(4), 465–71.CrossRefGoogle ScholarPubMed
Jia, X., Zhao, C., Li, P. et al. 2011. Sustained release of VEGF by coaxial electrospun dextran/PLGA fibrous membranes in vascular tissue engineering. J. Biomater. Sci. Polym. Edn., 22(13), 1811–27.CrossRefGoogle ScholarPubMed
Fu, K., Pack, D. W., Klibanov, A. M. and Langer, R. 2000. Visual evidence of acidic environment within degrading poly(lactic-co-glycolic acid) (PLGA) microspheres. Pharm. Res., 17(1), 100–6.CrossRefGoogle ScholarPubMed
Kim, H. K., Shim, W. S., Kim, S. E. et al. 2009. Injectable in situ-forming pH/thermo-sensitive hydrogel for bone tissue engineering. Tissue Eng. Part A, 15(4), 923–33.CrossRefGoogle ScholarPubMed
Ehrick, J. D., Deo, S. K., Browning, T. W. et al. 2005. Genetically engineered protein in hydrogels tailors stimuli-responsive characteristics. Nature Mater., 4(4), 298–302.CrossRefGoogle ScholarPubMed
Klouda, L. and Mikos, A. G. 2008. Thermoresponsive hydrogels in biomedical applications. Eur. J. Pharm. Biopharm., 68(1), 34–45.CrossRefGoogle ScholarPubMed
Geiger, M., Li, R. H. and Friess, W. 2003. Collagen sponges for bone regeneration with rhBMP-2. Adv. Drug Deliv. Rev., 55(12), 1613–29.CrossRefGoogle ScholarPubMed
Yamamoto, M., Takahashi, Y. and Tabata, Y. 2006. Enhanced bone regeneration at a segmental bone defect by controlled release of bone morphogenetic protein-2 from a biodegradable hydrogel. Tissue Eng., 12(5), 1305–11.CrossRefGoogle Scholar
Kolambkar, Y. M., Boerckel, J. D., Dupont, K. M. et al. 2011. Spatiotemporal delivery of bone morphogenetic protein enhances functional repair of segmental bone defects. Bone, 49(3), 485–92.CrossRefGoogle ScholarPubMed
Cao, H. and Kuboyama, N. 2010. A biodegradable porous composite scaffold of PGA/beta-TCP for bone tissue engineering. Bone, 46(2), 386–95.CrossRefGoogle ScholarPubMed
Wei, G., Jin, Q., Giannobile, W. V. and Pa, P. X. 2007. The enhancement of osteogenesis by nano-fibrous scaffolds incorporating rhBMP-7 nanospheres. Biomaterials, 28(12), 2087–96.CrossRefGoogle ScholarPubMed
Street, J., Bao, M., deGuzman, L. et al. 2002. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc. Nat. Acad. Sci. USA, 99(15), 9656–61.CrossRefGoogle ScholarPubMed
Lutolf, M. P., Weber, F. E., Schmoekel, H. G. et al. 2003. Repair of bone defects using synthetic mimetics of collagenous extracellular matrices. Nature Biotechnol., 21(5), 513–8.CrossRefGoogle ScholarPubMed
Patel, Z. S., Young, S., Tabata, Y. et al. 2008. Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model. Bone, 43(5), 931–40.CrossRefGoogle Scholar
Kanczler, J. M., Ginty, P. J., White, L. et al. 2010. The effect of the delivery of vascular endothelial growth factor and bone morphogenic protein-2 to osteoprogenitor cell populations on bone formation. Biomaterials, 31(6), 1242–50.CrossRefGoogle ScholarPubMed
Kempen, D. H., Lu, L., Heijink, A. et al. 2009. Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration. Biomaterials, 30(14), 2816–25.CrossRefGoogle ScholarPubMed
Manning, C. N., Kim, H. M., Sakiyama-Elbert, S. et al. 2011. Sustained delivery of transforming growth factor beta three enhances tendon-to-bone healing in a rat model. J. Orthop. Res., 29(7), 1099–105.CrossRefGoogle Scholar
Kovacevic, D., Fox, A. J., Bedi, A. et al. 2011. Calcium-phosphate matrix with or without TGF-β3 improves tendon-bone healing after rotator cuff repair. Am. J. Sports Med., 39(4), 811–19.CrossRefGoogle ScholarPubMed
Falco, E. E., Wang, M. O., Thompson, J. A. et al. 2011. Porous EH and EH-PEG scaffolds as gene delivery vehicles to skeletal muscle. Pharm. Res., 28(6), 1306–16.CrossRefGoogle ScholarPubMed
Liu, J. J., Wang, C. Y., Wang, J. G., Ruan, H. J. and Fan, C. Y. 2011. Peripheral nerve regeneration using composite poly(lactic acid-caprolactone)/nerve growth factor conduits prepared by coaxial electrospinning. J. Biomed. Mater. Res. A, 96(1), 13–20.CrossRefGoogle ScholarPubMed
de Boer, R., Knight, A. M., Borntraeger, A. et al. 2011. Rat sciatic nerve repair with a poly-lactic-co-glycolic acid scaffold and nerve growth factor releasing microspheres. Microsurgery, 31(4), 293–302.CrossRefGoogle ScholarPubMed
Kokai, L. E., Bourbeau, D., Weber, D., McAtee, J. and Marra, K. G. 2011. Sustained growth factor delivery promotes axonal regeneration in long gap peripheral nerve repair. Tissue Eng. Part A, 17(9–10), 1263–75.CrossRefGoogle ScholarPubMed
Angeloni, N. L., Bond, C. W., Tang, Y. et al. 2011. Regeneration of the cavernous nerve by Sonic hedgehog using aligned peptide amphiphile nanofibers. Biomaterials, 32(4), 1091–101.CrossRefGoogle ScholarPubMed
Davis, M. E., Hsieh, P. C., Takahashi, T. et al. 2006. Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction. Proc. Nat. Acad. Sci. USA, 103(21), 8155–60.CrossRefGoogle ScholarPubMed
Ruvinov, E., Leor, J. and Cohen, S. 2011. The promotion of myocardial repair by the sequential delivery of IGF-1 and HGF from an injectable alginate biomaterial in a model of acute myocardial infarction. Biomaterials, 32(2), 565–78.CrossRefGoogle Scholar
Segers, V. F., Tokunou, T., Higgins, L. J. et al. 2007. Local delivery of protease-resistant stromal cell derived factor-1 for stem cell recruitment after myocardial infarction. Circulation, 116(15), 1683–92.CrossRefGoogle ScholarPubMed
Sloan, A. J. and Smith, A. J. 1999. Stimulation of the dentine–pulp complex of rat incisor teeth by transforming growth factor-β isoforms 1–3 in vitro. Arch. Oral Biol., 44(2), 149–56.CrossRefGoogle ScholarPubMed
Dobie, K., Smith, G., Sloan, A. J. and Smith, A. J. 2002. Effects of alginate hydrogels and TGF-β1 on human dental pulp repair in vitro. Connect. Tissue Res., 43(2–3), 387–90.CrossRefGoogle ScholarPubMed
Sloan, A. J., Rutherford, R. B. and Smith, A. J. 2000. Stimulation of the rat dentine–pulp complex by bone morphogenetic protein-7 in vitro. Arch. Oral Biol., 45(2), 173–7.CrossRefGoogle ScholarPubMed
Nakashima, M. 1994. Induction of dentin formation on canine amputated pulp by recombinant human bone morphogenetic proteins (BMP)-2 and -4. J. Dent. Res., 73(9), 1515–22.CrossRefGoogle ScholarPubMed
Kim, J. Y., Xin, X., Moioli, E. K. et al. 2010. Regeneration of dental-pulp-like tissue by chemotaxis-induced cell homing. Tissue Eng. Part A, 16(10), 3023–31.CrossRefGoogle ScholarPubMed
Murakami, S., Takayama, S., Kitamura, M. et al. 2003. Recombinant human basic fibroblast growth factor (bFGF) stimulates periodontal regeneration in class II furcation defects created in beagle dogs. J. Periodontal Res., 38(1), 97–103.CrossRefGoogle ScholarPubMed
Takayama, S., Yoshida, J., Hirano, H. et al. 2002. Effects of basic fibroblast growth factor on human gingival epithelial cells. J. Periodontol., 73(12), 1467–73.CrossRefGoogle ScholarPubMed
Wikesjö, U. M., Lim, W. H., Thomson, R. C. et al. 2004. Periodontal repair in dogs: effect of recombinant human bone morphogenetic protein-12 (rhBMP-12) on regeneration of alveolar bone and periodontal attachment. J. Clin. Periodontol., 31(8), 662–70.CrossRefGoogle ScholarPubMed
King, G. N., King, N. and Hughes, F. J. 1998. Effect of two delivery systems for recombinant human bone morphogenetic protein-2 on periodontal regeneration in vivo. J. Periodontal Res., 33(4), 226–36.CrossRefGoogle ScholarPubMed
Cooke, J. W., Sarment, D. P., Whitesman, L. A. et al. 2006. Effect of rhPDGF-BB delivery on mediators of periodontal wound repair. Tissue Eng., 12(6), 1441–50.CrossRefGoogle ScholarPubMed
Kim, K., Lee, C. H., Kim, B. K. and Mao, J. J. 2010. Anatomically shaped tooth and periodontal regeneration by cell homing. J. Dent. Res., 89(8), 842–7.CrossRefGoogle ScholarPubMed
Suzuki, T., Bessho, K., Fujimura, K. et al. 2002. Regeneration of defects in the articular cartilage in rabbit temporomandibular joints by bone morphogenetic protein-2. Br. J. Oral Maxillofac. Surg., 40(3), 201–6.CrossRefGoogle ScholarPubMed
Ueki, K., Takazakura, D., Marukawa, K. et al. 2003. The use of polylactic acid/polyglycolic acid copolymer and gelatin sponge complex containing human recombinant bone morphogenetic protein-2 following condylectomy in rabbits. J. Craniomaxillofac. Surg., 31(2), 107–14.CrossRefGoogle ScholarPubMed
Holland, T. A., Bodde, E. W., Baggett, L. S. et al. 2005. Osteochondral repair in the rabbit model utilizing bilayered, degradable oligo(poly(ethylene glycol) fumarate) hydrogel scaffolds. J. Biomed. Mater. Res. A, 75(1), 156–67.CrossRefGoogle ScholarPubMed
Na, K., Kim, S., Woo, D. G. et al. 2007. Synergistic effect of TGFβ-3 on chondrogenic differentiation of rabbit chondrocytes in thermo-reversible hydrogel constructs blended with hyaluronic acid by in vivo test. J. Biotechnol., 128(2), 412–22.CrossRefGoogle ScholarPubMed
Reddi, A. H. 1998. Role of morphogenetic proteins in skeletal tissue engineering and regeneration. Nature Biotechnol., 16(3), 247–52.CrossRefGoogle ScholarPubMed
Lind, M., Eriksen, E. F. and Bunger, C. 1996. Bone morphogenetic protein-2 but not bone morphogenetic protein-4 and -6 stimulates chemotactic migration of human osteoblasts, human marrow osteoblasts, and U2-OS cells. Bone, 18(1), 53–7.CrossRefGoogle Scholar
Takaoka, K., Koezuka, M. and Nakahara, H. 1991. Telopeptide-depleted bovine skin collagen as a carrier for bone morphogenetic protein. J. Orthop. Res., 9(6), 902–7.CrossRefGoogle ScholarPubMed
Shields, L. B., Raque, G. H., Glassman, S. D. et al. 2006. Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion. Spine, 31(5), 542–7.CrossRefGoogle ScholarPubMed
Garrison, K. R., Donell, S., Ryder, J. et al. 2007. Clinical effectiveness and cost-effectiveness of bone morphogenetic proteins in the non-healing of fractures and spinal fusion: a systematic review. Health Technol. Assess., 11(30), 1–150 and iii–iv.CrossRefGoogle ScholarPubMed
Carano, R. A. and Filvaroff, E. H. 2003. Angiogenesis and bone repair. Drug Discov. Today, 8(21), 980–9.CrossRefGoogle ScholarPubMed

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