Skip to main content

Growth Factor Delivery for Tissue Engineering

Abstract

A tissue-engineered implant is a biologic-biomaterial combination in which some component of tissuehas been combined with a biomaterial to create a device for the restoration or modification of tissue ororgan function. Specific growth factors, released from a delivery device or from co-transplanted cells,would aid in the induction of host paraenchymal cell infiltration and improve engraftment of co-deliveredcells for more efficient tissue regeneration or ameliorate disease states. The characteristic properties ofgrowth factors are described to provide a biological basis for their use in tissue engineered devices. Theprinciples of polymeric device development for therapeutic growth factor delivery in the context of tissueengineering are outlined. A review of experimental evidence illustrates examples of growth factor deliveryfrom devices such as micropaticles, scaffolds, and encapsulated cells, for their use in the applicationareas of musculoskeletal tissue, neural tissue, and hepatic tissue.

This is a preview of subscription content, access via your institution.

REFERENCES

  1. I. A. McKay and I. Leigh. Growth Factors: A Practical Approach IRL Press, Oxford, 1993.

    Google Scholar 

  2. G. Ahrendt, D. E. Chickering, and J. P. Ranieri. Angiogenic growth factors: A review for tissue engineering. Tissue Eng. 4:117–130 (1998).

    Google Scholar 

  3. J. M. Schmitt, K. Hwang, S. R. Winn, and J. O. Hollinger. Bone morphogenetic proteins: An update on basic biology and clinical relevance. J. Orthop. Res. 17:269–278 (1999).

    Google Scholar 

  4. D. F. Bowen-Pope, T. W. Malpass, D. M. Foster, and R. Ross. Platelet-derived growth factor in vivo: Levels, activity, and rate of clearance. Blood 64:458–469 (1984).

    Google Scholar 

  5. R. Langer and M. Moses. Biocompatible controlled release polymers for delivery of polypeptides and growth factors. J. Cell. Biochem. 45:340–345 (1991).

    Google Scholar 

  6. S. P. Baldwin and W. M. Saltzman. Materials for protein delivery in tissue engineering. Adv. Drug Del. Rev. 33:71–86 (1998).

    Google Scholar 

  7. Y. H. Bae and S. W. Kim. Drug Delivery. In C. W. Patrick, A. G. Mikos, and L. V. McIntire. (eds.). Frontiers In Tissue Engineering. Elsevier Science Inc., Oxford, UK, 1998, pp. 261–277.

    Google Scholar 

  8. H. Lo, S. Kadiyala, S. E. Guggino, and K. W. Leong. Poly(L-lactic acid) foams with cell seeding and controlled-release capacity. J. Biomed. Mater. Res. 30:475–484 (1996).

    Google Scholar 

  9. K. Whang, D. C. Tsai, E. K. Nam, M. Aitken, S. M. Sprague, P. K. Patel, and K. E. Healy. Ectopic bone formation via rhBMP-2 delivery from porous bioabsorbable polymer scaffolds. J. Biomed. Mater. Res. 42:491–499 (1998).

    Google Scholar 

  10. N. Fournier and C. J. Doillon. Biological molecule-impregnated polyester: An in vivo angiogenesis study. Biomaterials 17:1659–665 (1996).

    Google Scholar 

  11. Y. Tabata, A. Nagano, and Y. Ikada. Biodegradation of hydrogel carrier incorporating fibroblast growth factor. Tissue Eng. 5: 127–138 (1999).

    Google Scholar 

  12. K. Whang, T. K. Goldstick, and K. E. Healy. Controlled release of macromolecules from bioabsorbable emulsion freeze-dried scaffolds: In vitro protein release. J. Controlled Rel. (in press)

  13. D. J. Mooney, P. M. Kaufmann, K. Sano, S. P. Schwendeman, K. Majahod, B. Schloo, J. P. Vacanti, and R. Langer. Localized delivery of epidermal growth factor improves the survival of transplanted hepatocytes. Biotechnol. Bioeng. 50:422–429 (1996).

    Google Scholar 

  14. J. E. Babensee, J. M. Anderson, L. V. McIntire, and A. G. Mikos. Host response to tissue engineered devices. Adv. Drug Del. Rev. 33:111–139 (1998).

    Google Scholar 

  15. M. S. Schoichet, F. T. Gentile, and S. R. Winn. The use of polymers in the treatment of neurological disorders A discussion emphasizing encapsulated cell therapy. TRIP 3:374–380 (1995).

    Google Scholar 

  16. I. Ito, G. Chen, and Y. Imanishi. Artificial juxtacrine stimulation for tissue engineering. J. Biomater. Sci. Polym. Ed. 9:879–890 (1998).

    Google Scholar 

  17. S. T. Carbonetto, M. M. Gruver, and D. C. Turner. Nervefiber growth on defined hydrogel substrates. Science 216:897–899 (1982).

    Google Scholar 

  18. P. R. Kuhl and L. G. Griffith-Cima. Tethered epidermal growth factor as a paradigm for growth factor-induced stimulation from the solid phase. Nature Med. 2:1022–1027 (1996).

    Google Scholar 

  19. J. M. Anderson. Biocompatibility of tissue-engineered implants. In C. W. Patrick, A. G. Mikos, and L. V. McIntire (eds.). Frontiers In Tissue Engineering. Elsevier Science Inc., Oxford, UK. 1998, pp. 152–165.

    Google Scholar 

  20. J. A. Hubbell. Biomaterials in tissue engineering. Biotechnology 13:565–576 (1995).

    Google Scholar 

  21. M. E. Nimni. Polypeptide growth factors: Targeted delivery systems. Biomaterials 18:1201–1225 (1997).

    Google Scholar 

  22. K. Whang, K. E. Healy, D. R. Elenz, E. K. Nam, D. C. Tsai, C. H. Thomas, G. W. Nuber, F. H. Glorieux, R. Travers, and S. M. Sprague. Engineering bone regeneration with bioabsorbable scaffolds with novel microarchitecture. Tissue Eng. 5:35–51 (1999).

    Google Scholar 

  23. J. N. Beresford. Osteogenic stem cells and the stromal system of bone and marrow. Clin. Orthop. 240:270–280 (1989).

    Google Scholar 

  24. J. H. Brekke. A rationale for delivery of osteoinductive proteins. Tissue Eng. 2:97–114 (1996).

    Google Scholar 

  25. E. A. Wang, D. I. Israel, S. Kelly, and D. P. Luxenberg. Bone morphogenetic protein-2 causes commitment and differentiation of C3H10T1/2 and 3T3 cells. Growth Factors 9:57–71 (1993).

    Google Scholar 

  26. I. Asahina, T. K. Sampath, and P. V. Hauschka. Human osteogenic protein-1 induces chondroblastic, osteoblastic, and/or adipocytic differentiation of clonal murine target cells. Exp. Cell Res. 222:38–47 (1996).

    Google Scholar 

  27. A. Rezania, C. H. Thomas, A. B. Branger, C. M. Waters, and K. E. Healy. Detachment strength and morphology of bone cells contacting materials modified with a peptide sequence found within bone sialoprotein. J. Biomed. Mater. Res. 37:9–19 1997).

    Google Scholar 

  28. A. I. Caplan. Cartilage begets bone versus endochondral myelopoiesis. Clin. Orthop. 261:257–267 (1990).

    Google Scholar 

  29. H. Uludag, D. D'Augusta, R. Palmer, G. Timony, and J. Wozney. Characterization of rhBMP-2 pharmacokinetics implanted with biomaterial carriers in the rat ectopic model. J. Biomed. Mater. Res. 46:193–202 (1999).

    Google Scholar 

  30. H. Bentz, J. A. Schroeder, and T. D. Estridge. Improved local delivery of TGF-β2 by binding to injectable fibrillar collagen via difunctional polyethylene glycol. J. Biomed. Mater. Res. 39: 539–548 (1998).

    Google Scholar 

  31. Y. Tabata, A. Nagano, M. Muniruzzaman, and Y. Ikada. In vitro sorption and desorption of basic fibroblast growth factor from biodegradable hydrogels. Biomaterials 19:1781–1789 (1998).

    Google Scholar 

  32. Y. Tabata, K. Yamada, S. Miyamoto, I. Nagata, H. Kikuchi, I. Aoyama, M. Tamura, and Y. Ikada. Bone regeneration by basic fibroblast growth factor complexed with biodegradable hydrogels. Biomaterials 19:807–815 (1998).

    Google Scholar 

  33. L. Hong, Y. Tabata, M. Yamamoto, S. Miyamoto, K. Yamada, N. Hashimoto, and Y. Ikada. Comparison of bone regeneration in a rabbit skull defect by recombinant human BMP-2 incorporated in biodegradable hydrogel and in solution. J. Biomater. Sci. Polym. Ed. 9:1001–1014 (1998).

    Google Scholar 

  34. J. O. Hollinger, J. M. Schmitt, D. C. Buck, R. Shannon, S-P. Joh, H. D. Zegzula, and J. Wozney. Recombinant human bone morpholgenetic protein-2 and collagen for bone regeneration. J. Biomed. Mater. Res. (Appl. Biomater.). 43:356–364 (1998).

    Google Scholar 

  35. D. L. Wheeler, D. L. Chamberland, J. M. Schmitt, D. C. Buck, J. H. Brekke, J. O. Hollinger, S-P. Joh, and K-W. Suh. Radiomorphometry and biomechanical assessment of recombinant human bone morphogenetic protein 2 and polymer in rabbit radius ostectomy model. J. Biomed. Mater. Res. 43:365–373 (1998).

    Google Scholar 

  36. Y. J. Park, Y. Ku, C. P. Chung, and S. J. Lee. Controlled release of platelet-derived growth factor from porous poly(L-lactide) membranes for guided tissue regeneration. J. Contr. Rel. 51:201–211 (1998).

    Google Scholar 

  37. J. H. Brekke and J. M. Toth. Principles of tissue engineering applied to programmable osteogenesis. J. Biomed. Mater. Res. (Appl. Biomater.). 43:380–398 (1998).

    Google Scholar 

  38. G. Zellin and A. Linde. Importance of delivery systems for growth-stimulatory factors in combination with osteopromotive membranes. An experimental study using rhBMP-2 in rat mandibular defects. J. Biomed. Mater. Res. 35:181–190 (1997).

    Google Scholar 

  39. S. C. Lee, M. Shea, M. A. Battle, K. Kozitza, E. Ron, T. Turek, R. G. Schaub, and W. C. Hayes. Healing of large segmental defects in rat femurs is aided by RhBMP-2 in PLGA matrix. J. Biomed. Mater. Res. 28:1149–1156 (1994).

    Google Scholar 

  40. R. Kenley, L. Marden, T. Turek, L. Jin, E. Ron, and J. O. Hollinger. Osseous regeneration in the rat calvarium using novel delivery systems for recombinant human bone morphogenetic protein-s (rhBMP-2). J. Biomed. Mater. Res. 28:1139–1147 (1994).

    Google Scholar 

  41. K. Ohura, C. Hamanishi, S. Tanaka, and N. Matsuda. Healing of segmental bone defects in rats induced by a β-TCP-MCPM cement combined with rhBMP-2. J. Biomed. Mater. Res. 44: 168–175 (1999).

    Google Scholar 

  42. D. M. Arm, A. F. Tencer, S. D. Bain, and D. Celino. Effect of controlled release of platelet-derived growth factor from a porous hydroxyapatite implant on bone ingrowth. Biomaterials 17:703–709 (1996).

    Google Scholar 

  43. J. M. Schmitt, D. Buck, S. Bennett, W. Skalla, C. Christoforou, D. Buechter, E. Gruskin, and J. O. Hollinger. Assessment of an experimental bone wax polymer plus TGF-β1 implanted into calvarial defects. J. Biomed. Mater. Res. 41:584–592 (1998).

    Google Scholar 

  44. S. R. Winn, J. M. Schmitt, D. Buck, Y. Hu, D. Grainger, and J. O. Hollinger. Tissue-engineered bone biomimetic to regenerate calvarial critical-sized defects in athymic rats. J. Biomed. Mater. Res. 45:414–421 (1999).

    Google Scholar 

  45. S. A. Tan and P. Aebischer. The problems of delivering neuroactive molecules to the CNS. Ciba Foundation Symposium 196:211–239 (1996).

    Google Scholar 

  46. M. F. Haller and W. M. Saltzman. Nerve growth factor delivery systems. J. Controlled Release 53:1–6 (1998).

    Google Scholar 

  47. P. A. Starr, T. Wichmann, C. van Horne, and R. A. Bakay. Intranigral transplantation of fetal substantia nigra allograft in the hemiparkinsonian rhesus monkey. Cell Transplant. 8:37–45 (1999).

    Google Scholar 

  48. P. A. Trsco. Encapsulated cells for sustained neurotransmitter delivery to the central nervous system. J. Controlled Release 28:253–258 (1994).

    Google Scholar 

  49. J. Sautter, J. L. Tseng, D. Braguglia, P. Aebischer, C. Spenger, R. W. Seiler, H. R. Widmer, and A. D. Zurn. Implants of polymer-encapsulated genetically modified cells releasing glial cell line derived neurotrophic factor improve survival, growth, and function of fetal dopaminergic grafts. Exp. Neurol. 149:230–236 (1998).

    Google Scholar 

  50. M. H. Tuszynski and N. Weidner. Grafts of genetically modified Schwann cells to the spinal cord: Survival, axon growth and myelination. Cell Transplant 7:185–194 (1998).

    Google Scholar 

  51. J. H. Kordower, S. R. Winn, Y-T. Liu, E. J. Mufson, J. R. Sladek, J. P. Hammang, E. E. Baetge, and D. F. Emerich. The aged monkey basal forebrain: rescue and sprouting of axotomized basal forebrain neurons after grafts of encapsulated cells secreting human nerve growth factor. Proc. Natl. Acad. Sci. USA 91:10898–10902 (1994).

    Google Scholar 

  52. D. F. Emerich, J. P. Mammang, E. E. Baetge, and S. R. Winn. Implantation of polymer-encapsulated nerve growth factor-secreting fibroblasts attenuates the behavioral and neoropathological consequences of quinolinic acid injections into rodent striatum. Exp. Neurol. 130:141–150 (1994).

    Google Scholar 

  53. M. D. Lidner, S. R. Winn, E. E. Baetge, J. P. Hammang, F. T. Gentile, E. Doherty, P. E. McDermott, B. Frydel, D. Ullman, T. Schallert, and D. F. Emerich. Implantation of encapsulated catecholamine and GDNF-producing cells in rats with unilateral dopamine depletions and Parkinsonian symptoms. Exp. Neurol. 132:62–76 (1995).

    Google Scholar 

  54. P. Aebischer, M. Schluep, N. Deglon, J-M. Joseph, L. Hirt, B. Heyd, M. Goddard, J. P. Hammang, A. D. Zurn, A. C. Kato, F. Regli, and E. E. Baetge. Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients. Nature Med. 2:696–699 (1996).

    Google Scholar 

  55. S. R. Winn, J. P. Hammang, D. F. Emerich, A. Lee, R. D. Palmiter, and E. E. Baetge. Polymer-encapsulated cells genetically modified to secrete human nerve growth factor promote the survival of axotomized septal cholinergic neurons. Proc. Natl. Acad. Sci. USA 91:2324–2328 (1994).

    Google Scholar 

  56. R. Vejsada, J. L. Tseng, R. M. Lindsay, A. Acheson, P. Aebischer, and A. C. Kato. Synergistic but transient rescue effects of BDNF and GDNF on axotomized neonatal motoneurons. Neurosci. 84:129–139 (1998).

    Google Scholar 

  57. P. Aebischer, A. N. Salessiotis, and S. R. Winn. Basic fibroblast growth factor released from synthetic guidance channels facilitates peripheral nerve regeneration across long nerve gaps. J. Neurosci. Res. 23:282–289 (1989).

    Google Scholar 

  58. V. Guenard, N. Kleitman, T. K. Morrissey, R. P. Bunge, and P. Aebischer. Syngeneic Schwann cells derived from adult nerves seeded in semipermeable guidance channels enhance peripheral nerve regeneration. J. Neurosci. 12:3310–3320 (1992).

    Google Scholar 

  59. X. M. Xu, V. Guenard, N. Kleitman, P. Aebischer, and M. B. Bunge. A combination of BDNF and NT-3 promotes supraspinal axonal regeneration into Schwann cell grafts in adult rat thoracic spinal cord. Exp. Neurol. 134:261–272 (1995).

    Google Scholar 

  60. W. F. A. Den Dunnen, I. Stokroos, E. H. Blaauw, A. Holwerda, A. J. Pennings, P. H. Robinson, and J. M. Schakenraad. Light microscopic and electron-microscopic evaluation of short-term nerve regeneration using a biodegradable poly(DL-lactide-ɛ-caprolactone) nerve guides. J. Biomed. Mater. Res. 31:105–115 (1996).

    Google Scholar 

  61. M. S. Widmer, P. K. Gupta, L. Lu, R. K. Meszlenyi, G. R. D. Evans, K. Brandt, T. Savel, A. Gurlek, C. W. Patrick, and A. G. Mikos. Manufacture of porous biodegradable polymer conduits by an extrusion process for guided tissue regeneration. Biomaterials 19:1945–1955 (1998).

    Google Scholar 

  62. F. Langone, S. Lora, F. M. Veronese, P. Caliceti, P. P. Parnigotto, F. Valenti, and G. Palma. Peripheral nerve repair using a poly(organo)phosphazene tubular prosthesis. Biomaterials 16:347–353 (1995).

    Google Scholar 

  63. M. H. Spilker, I. V. Yannas, H. P. Hsu, T. V. Norregaard, S. K. Kostyk, and M. Spector. The effects of collagen-based implants on early healing of the adult rat spinal cord. Tissue Eng. 3:309–317 (1997).

    Google Scholar 

  64. X. J. Tong, K. Hirai, H. Shimada, Y. Mizutani, T. Izumi, N. Toda, and P. Yu. Sciatic nerve regeneration navigated by laminin-fibronectin double coated biodegradable collagen grafts in rats. Brain Res. 663:155–162 (1994).

    Google Scholar 

  65. B. R. Sickel, D. Jones, K. J. Hekimian, K. K. Wong, D. P. Chakalis, and P. D. Costas. Hyaluronic acid through a new injectable nerve guide delivery system enhances peripheral nerve regeneration in the rat. J. Neurosci. Res. 40:318–324 (1995).

    Google Scholar 

  66. E. M. Powell, M. R. Sobarzo, and W. M. Saltzman. Controlled release of nerve growth factor from a polymeric implant. Brain Res. 515:309–311 (1990).

    Google Scholar 

  67. X. Cao and M. S. Schoichel. Delivering neuroactive molecules from biodegradable microspheres for application in central nervous system disorders. Biomaterials 20:329–339 (1999).

    Google Scholar 

  68. C. E. Krewson and W. M. Saltzman. Transport and elimination of recombinant human NGF during long-term delivery to the brain. Brain Res. 727:169–181 (1996).

    Google Scholar 

  69. C. E. Krewson, R. Dause, M. Mak, and W. M. Saltzman. Stabilization of nerve growth factor in controlled release polymers and in tissue. J. Biomater. Sci. Polym. Ed. 8:103–117 (1996).

    Google Scholar 

  70. N. Belcheva, K. Woodrow-Mumford, M. J. Mahoney, and W. M. Saltzman. Synthesis and biological activity of polyethylene glycol-mouse nerve growth factor conjugate. Bioconjug. Chem. 10:932–937 (1999).

    Google Scholar 

  71. D. J. Mooney, S. Park, P. M. Kaufmann, K. Sano, K. McNamara, J. P. Vacanti, and R. Langer. Biodegradable sponges for hepatocyte transplantation. J. Biomed. Mater. Res. 29:959–965 (1995).

    Google Scholar 

  72. D. J. Mooney, K. Sano, P. M. Kaufmann, K. Majahod, B. Schloo, J. P. Vacanti, and R. Langer. Long-term engraftment of heptocytes transplanted on biodegradable polymer sponges. J. Biomed. Mater. Res. 37:413–420 (1997).

    Google Scholar 

  73. N. Fausto. Growth factors in liver development, regeneration, and carcinogenesis. Prog. Growth Factor Res. 3:219–234 (1991).

    Google Scholar 

  74. T. H. Kim, H. M. Lee, H. Utsonomiya, P. Ma, R. Langer, E. V. Schmidt, and J. P. Vacanti. Enhanced survival of transgenic hepatocytes expressing hepatocyte growth factor in hepatocyte tissue engineering. Transplant. Proc. 29:858–860 (1997).

    Google Scholar 

  75. C. Ricordi, P. E. Lacy, M. P. Callery, P. W. Park, and M. W. Flye. Tropic factors from pancreatic islets ion combined hepatocyte-islet allografts enhance hepatocellular survival. Surgery 105: 218–223 (1989).

    Google Scholar 

  76. P. M. Kaufmann, K. Sano, S. Ukama, and J. P. Vacanti. Heterotopic hepatocyte transplantation using three-dimensional polymers. Evaluation of the stimulatory effects by portacaval shunt or islet cell co-transplantation. Transplant. Proc. 26:3343–3345 (1994).

    Google Scholar 

  77. Y. M. Elcin, V. Dixit, K. Lewin, and G. Gitnick. Xenotransplantation of fetal porcine hepatocytes in rats using a tissue engineering approach. Artificial Organs 23:146–152 (1999).

    Google Scholar 

  78. J. O. Hollinger and K. Leong. Poly(α-hydroxy acids): Carriers for bone morphogenetic proteins. Biomaterials 17:187–194 (1996).

    Google Scholar 

  79. M. Isobe, Y. Yamazaki, M. Mori, K. Ishihara, N. Nakabashi, and T. Amagasa. The role of recombinant human bone morphogenetic protein-2 in PLGA capsules at an extraskeletal site of the rat. J. Biomed. Mater. Res. 45:36–41 (1999).

    Google Scholar 

  80. Y. Kuboki, H. Takita, D. Kobayashi, E. Tsurugea, M. Inoue, M. Murata, N. Nagai, Y. Dohi, and H. Ohgushi. BMP-induced osteogenesis on the surface of hydroxyapatite with geometrically feasible and nonfeasible structures: Topology of osteogenesis. J. Biomed. Mater. Res. 39:190–199 (1998).

    Google Scholar 

  81. B. D. Boyan, C. H. Lohmann, A. Somers, G. G. Niederauer, J. M. Wozney, D. D. Dean, D. L. Carnes, and Z. Schwartz. Potential of porous poly-D,L-lactide-co-glycolide particles as a carrier for recombinant bone morphogenetic protein-2 during osteoinduction in vivo. J. Biomed. Mater. Res. 46:51–59 (1999).

    Google Scholar 

  82. E. M. Santos, S. Radin, B. J. Shenker, I. M. Shapiro, and P. Ducheyne. Si-Ca-P xerogels and bone morphogenetic protein act synergistically on rat stromal marrow cell differentitation in vitro. Biomed. Mater. Res. 41:87–94 (1998).

    Google Scholar 

  83. P. J. Boyne, R. E. Marx, M. Nevins, G. Triplett, E. Lazaro, L. C. Lilly, M. Alder, and P. Nummikoski. A feasibility study evaluation rhBMP-2/absorbable collagen sponge for maxillary sinus augmentation. Int. J. Periodont. Restor. Dent. 17:11–25 (1997).

    Google Scholar 

  84. M. Yamamoto, Y. Tabata, and Y. Ikada. Ectopic bone formation by biodegradable hydrogels incorporating morphogenetic protein. J. Biomater. Sci. Polym. Ed. 9:439–458 (1998).

    Google Scholar 

  85. M. L. Renier and D. H. Kohn. Development and characterization of a biodegradable polyphosphate. J. Biomed. Mater. Res. 34:95–104 (1997).

    Google Scholar 

  86. L. Lu, G. N. Stamatas, and A. G. Mikos. Controlled release of transforming growth factor-β1 from biodegradable polymer microparticles. J. Biomed. Mater. Res. (in press).

  87. S. J. Peter, L. Lu, D. J. Kim, G. N. Stamatas, M. J. Miller, M. J. Yaszemski, and A. G. Mikos. Effects of transforming growth factor-β1 released from biodegradable polymer microparticles on marrow stromal cells cultured on poly(propylene fumarate) substrates. J. Biomed. Mater. Res. (in press).

  88. W. R. Gombotz, S. C. Sankey, L. S. Bouchard, J. Ranchalis, and P. Puolakkainen. Controlled release of TGF-β from a biodegradable matrix for bone regeneration. J. Biomater. Sci. Polym. Ed. 5:49–63 (1993).

    Google Scholar 

  89. S. B. Nicoll, S. Radin, E. M. Santos, R. S. Tuan, and P. Ducheyne. In vitro release kinetics of biologically active transforming growth factor-β1 from a novel porous glass carrier. Biomaterials 18: 853–859 (1997).

    Google Scholar 

  90. H. D. Kim and R. F. Valentini. Human osteoblast response in vitro to platelet-derived growth factor and transforming growth factor-β delivered from controlled-release polymer rods. Biomaterials 18:1175–1184 (1997).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Babensee, J.E., McIntire, L.V. & Mikos, A.G. Growth Factor Delivery for Tissue Engineering. Pharm Res 17, 497–504 (2000). https://doi.org/10.1023/A:1007502828372

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1007502828372

  • tissue engineering
  • growth factors
  • controlled release
  • bone
  • nerve
  • liver