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Cell and Tissue Interactions with Materials: The Role of Growth Factors

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Biological Interactions on Materials Surfaces

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Abstract

Realization and appreciation that growth factors are essential in tissue development, regeneration, and maintenance as well as crucial mediators/regulators of pertinent cellular- and molecular-level events has motivated new directions in bioengineering research. These endeavors have the potential of seminal contributions in implant biomaterials, tissue engineering, and regenerative medicine.

This chapter summarizes the current knowledge of the role of growth factors in the biology/physiology of two tissues, specifically, vascular tissue and bone. It also provides an overview of research endeavors directed at transferring and applying pertinent growth factor knowledge to biomaterials; delivery of the appropriate type, concentration, and timely sequence of bioactive growth factors, which promote interactions and functions of cells pertinent to neotissue formation, will enhance the long-term performance of implants, including tissue-engineering constructs. Future directions for research and development in these areas are outlined.

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Abbreviations

ACS:

absorbable collagen sponge

aFGF:

acidic fibroblast growth factor (equivalent to FGF-1)

ALK1:

activin receptor-like kinase 1

AMD:

age-related macular degeneration

AP:

alkaline phosphatase

bFGF:

basic fibroblast growth factor (equivalent to FGF-2)

BMC:

bone marrow cell

BMP:

bone morphogenetic protein

ECM:

extracellular matrix

FDA:

US Food and Drug Administration

FGF:

fibroblast growth factor

FGFR1:

fibroblast growth factor receptor 1

FGFR2:

fibroblast growth factor receptor 2

FGF-1:

fibroblast growth factor-1 (equivalent to aFGF)

FGF-2:

fibroblast growth factor-2 (equivalent to bFGF)

HSC:

hematopoietic stem cell(s)

hBMSC:

human bone-marrow stromal-cell

HA:

hydroxyapatite

HIF-1α:

hypoxia-inducible factor-1α

HUVEC:

human umbilical vein endothelial cell

IGF:

insulin-like growth factor

IGFBP:

insulin-like growth factor binding protein

MMP:

matrix metalloproteinase

mRNA:

messenger ribonucleic acid

Flt-1:

fms-related tyrosine kinase-1 (equivalent to VEGFR-1)

Flk-1:

kinase insert domain receptor (equivalent to VEGFR-2)

NO:

nitric oxide

PDGF:

platelet-derived growth factor

PDGFR:

platelet-derived growth factor receptor

PDGFR-α:

platelet-derived growth factor receptor-α

PDGFR-β:

platelet-derived growth factor receptor-β

PDLLA:

poly (d,l-lactide)

PLA:

poly(lactic acid)

PLGA:

poly(lactic-co-glycolic acid)

PEG:

polyethylene glycol

rhBMP-2:

recombinant human bone morphogenetic protein-2

SCID:

severe combined immunodeficiency

SS-PEG-SS:

disuccinimidyldiscuccinatepolyethyleneglycol

TGF:

transforming growth factor

TGF-β:

transforming growth factor-β

TGFβRI:

transforming growth factor-β receptor-I

TGFβRII:

transforming growth factor-β receptor-II

VEGF:

vascular endothelial growth factor

VEGFR:

vascular endothelial growth factor receptor

References

  1. Risau W, Flamme I. Vasculogenesis. Annu Rev Cell Dev Biol 1995;11:73–91.

    CAS  Google Scholar 

  2. Gonzalez-Crussi F. Vasculogenesis in the chick embryo. An ultrastructural study. Am J Anat 1971;130:441–460.

    CAS  Google Scholar 

  3. Drake CJ, Fleming PA. Vasculogenesis in the day 6.5 to 9.5 mouse embryo. Blood 2000;95:1671–1679.

    CAS  Google Scholar 

  4. Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, Jeltsch M, Mitchell C, Alitalo K, Shima D, Betsholtz C. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 2003;161:1163–1177.

    CAS  Google Scholar 

  5. Egginton S, Gerritsen M. Lumen formation: in vivo versus in vitro observations. Microcirculation 2003;10:45–61.

    Google Scholar 

  6. Hogan BL, Kolodziej PA. Organogenesis: molecular mechanisms of tubulogenesis. Nat Rev Genet 2002;3:513–523.

    CAS  Google Scholar 

  7. Ko HC, Milthorpe BK, McFarland CD. Engineering thick tissues-the vascularisation problem. Eur Cell Mater 2007;14:1–18; discussion 18–9.

    CAS  Google Scholar 

  8. Shibuya M. Vascular endothelial growth factor-dependent and -independent regulation of angiogenesis. BMB Rep 2008;41:278–286.

    CAS  Google Scholar 

  9. Gehling UM, Ergun S, Schumacher U, Wagener C, Pantel K, Otte M, Schuch G, Schafhausen P, Mende T, Kilic N, Kluge K, Schafer B, Hossfeld DK, Fiedler W. In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood 2000;95:3106–3112.

    CAS  Google Scholar 

  10. Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML, Schuh AC. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 1995;376:62–66.

    CAS  Google Scholar 

  11. Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O’Shea KS, Powell-Braxton L, Hillan KJ, Moore MW. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996;380:439–442.

    CAS  Google Scholar 

  12. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons L, Collen D, Risau W, Nagy A. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996;380:435–439.

    CAS  Google Scholar 

  13. Fong GH, Rossant J, Gertsenstein M, Breitman ML. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 1995;376:66–70.

    CAS  Google Scholar 

  14. Hiratsuka S, Minowa O, Kuno J, Noda T, Shibuya M. Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci USA 1998;95:9349–9354.

    CAS  Google Scholar 

  15. Lamalice L, Le Boeuf F, Huot J. Endothelial cell migration during angiogenesis. Circ Res 2007;100:782–794.

    CAS  Google Scholar 

  16. Lee SH, Schloss DJ, Swain JL. Maintenance of vascular integrity in the embryo requires signaling through the fibroblast growth factor receptor. J Biol Chem 2000;275:33679–33687.

    CAS  Google Scholar 

  17. Fruttiger M. Development of the retinal vasculature. Angiogenesis 2007;10:77–88.

    Google Scholar 

  18. Pepper MS, Ferrara N, Orci L, Montesano R. Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Biochem Biophys Res Commun 1992;189:824–831.

    CAS  Google Scholar 

  19. Yla-Herttuala S, Rissanen TT, Vajanto I, Hartikainen J. Vascular endothelial growth factors: biology and current status of clinical applications in cardiovascular medicine. J Am Coll Cardiol 2007;49:1015–1026.

    Google Scholar 

  20. Byrne AM, Bouchier-Hayes DJ, Harmey JH. Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF). J Cell Mol Med 2005;9:777–794.

    CAS  Google Scholar 

  21. Larcher F, Murillas R, Bolontrade M, Conti CJ, Jorcano JL. VEGF/VPF overexpression in skin of transgenic mice induces angiogenesis, vascular hyperpermeability and accelerated tumor development. Oncogene 1998;17:303–311.

    CAS  Google Scholar 

  22. Pettersson A, Nagy JA, Brown LF, Sundberg C, Morgan E, Jungles S, Carter R, Krieger JE, Manseau EJ, Harvey VS, Eckelhoefer IA, Feng D, Dvorak AM, Mulligan RC, Dvorak HF. Heterogeneity of the angiogenic response induced in different normal adult tissues by vascular permeability factor/vascular endothelial growth factor. Lab Invest 2000;80:99–115.

    CAS  Google Scholar 

  23. Springer ML, Chen AS, Kraft PE, Bednarski M, Blau HM. VEGF gene delivery to muscle: potential role for vasculogenesis in adults. Mol Cell 1998;2:549–558.

    CAS  Google Scholar 

  24. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 2004;25:581–611.

    CAS  Google Scholar 

  25. Gerber HP, Dixit V, Ferrara N. Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J Biol Chem 1998;273:13313–13316.

    CAS  Google Scholar 

  26. Miller-Kasprzak E, Jagodzinski PP. Endothelial progenitor cells as a new agent contributing to vascular repair. Arch Immunol Ther Exp (Warsz) 2007;55:247–259.

    CAS  Google Scholar 

  27. Ohneda O, Nagano M, Fujii-Kuriyama Y. Role of hypoxia-inducible factor-2alpha in endothelial development and hematopoiesis. Methods Enzymol 2007;435:199–218.

    CAS  Google Scholar 

  28. Brogi E, Schatteman G, Wu T, Kim EA, Varticovski L, Keyt B, Isner JM. Hypoxia-induced paracrine regulation of vascular endothelial growth factor receptor expression. J Clin Invest 1996;97:469–476.

    CAS  Google Scholar 

  29. Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J. Vascular-specific growth factors and blood vessel formation. Nature 2000;407:242–248.

    CAS  Google Scholar 

  30. Hood JD, Meininger CJ, Ziche M, Granger HJ. VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Am J Physiol 1998;274:H1054–8.

    CAS  Google Scholar 

  31. Holderfield MT, Hughes CC. Crosstalk between vascular endothelial growth factor, notch, and transforming growth factor-beta in vascular morphogenesis. Circ Res 2008;102:637–652.

    CAS  Google Scholar 

  32. Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z, Hanahan D. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2000;2:737–744.

    CAS  Google Scholar 

  33. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9:669–676.

    CAS  Google Scholar 

  34. Hillen F, Griffioen AW. Tumour vascularization: sprouting angiogenesis and beyond. Cancer Metastasis Rev 2007;26:489–502.

    Google Scholar 

  35. Seghezzi G, Patel S, Ren CJ, Gualandris A, Pintucci G, Robbins ES, Shapiro RL, Galloway AC, Rifkin DB, Mignatti P. Fibroblast growth factor-2 (FGF-2) induces vascular endothelial growth factor (VEGF) expression in the endothelial cells of forming capillaries: an autocrine mechanism contributing to angiogenesis. J Cell Biol 1998;141:1659–1673.

    CAS  Google Scholar 

  36. Claffey KP, Abrams K, Shih SC, Brown LF, Mullen A, Keough M. Fibroblast growth factor 2 activation of stromal cell vascular endothelial growth factor expression and angiogenesis. Lab Invest 2001;81:61–75.

    CAS  Google Scholar 

  37. Murakami M, Simons M. Fibroblast growth factor regulation of neovascularization. Curr Opin Hematol 2008;15:215–220.

    CAS  Google Scholar 

  38. Itoh N, Ornitz DM. Evolution of the Fgf and Fgfr gene families. Trends Genet 2004;20:563–569.

    CAS  Google Scholar 

  39. Nissen LJ, Cao R, Hedlund EM, Wang Z, Zhao X, Wetterskog D, Funa K, Brakenhielm E, Cao Y. Angiogenic factors FGF2 and PDGF-BB synergistically promote murine tumor neovascularization and metastasis. J Clin Invest 2007;117:2766–2777.

    CAS  Google Scholar 

  40. Millette E, Rauch BH, Kenagy RD, Daum G, Clowes AW. Platelet-derived growth factor-BB transactivates the fibroblast growth factor receptor to induce proliferation in human smooth muscle cells. Trends Cardiovasc Med 2006;16:25–28.

    CAS  Google Scholar 

  41. Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev 2008;22:1276–1312.

    CAS  Google Scholar 

  42. Bohnsack BL, Hirschi KK. Red light, green light: signals that control endothelial cell proliferation during embryonic vascular development. Cell Cycle 2004;3:1506–1511.

    CAS  Google Scholar 

  43. von Tell D, Armulik A, Betsholtz C. Pericytes and vascular stability. Exp Cell Res 2006;312:623–629.

    CAS  Google Scholar 

  44. Carmeliet P. Angiogenesis in health and disease. Nat Med 2003;9:653–660.

    CAS  Google Scholar 

  45. Elliott RL, Blobe GC. Role of transforming growth factor beta in human cancer. J Clin Oncol 2005;23:2078–2093.

    CAS  Google Scholar 

  46. Pepper MS. Transforming growth factor-beta: vasculogenesis, angiogenesis, and vessel wall integrity. Cytokine Growth Factor Rev 1997;8:21–43.

    CAS  Google Scholar 

  47. Pepper MS, Vassalli JD, Orci L, Montesano R. Biphasic effect of transforming growth factor-beta 1 on in vitro angiogenesis. Exp Cell Res 1993;204:356–363.

    CAS  Google Scholar 

  48. Dickson MC, Martin JS, Cousins FM, Kulkarni AB, Karlsson S, Akhurst RJ. Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice. Development 1995;121:1845–1854.

    CAS  Google Scholar 

  49. Goumans MJ, Lebrin F, Valdimarsdottir G. Controlling the angiogenic switch: a balance between two distinct TGF-b receptor signaling pathways. Trends Cardiovasc Med 2003;13:301–307.

    CAS  Google Scholar 

  50. Otrock ZK, Mahfouz RA, Makarem JA, Shamseddine AI. Understanding the biology of angiogenesis: review of the most important molecular mechanisms. Blood Cells Mol Dis 2007;39:212–220.

    CAS  Google Scholar 

  51. Pertovaara L, Kaipainen A, Mustonen T, Orpana A, Ferrara N, Saksela O, Alitalo K. Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells.J Biol Chem 1994;269:6271–6274.

    CAS  Google Scholar 

  52. Molin DG, DeRuiter MC, Wisse LJ, Azhar M, Doetschman T, Poelmann RE, Gittenberger-de Groot AC. Altered apoptosis pattern during pharyngeal arch artery remodelling is associated with aortic arch malformations in Tgfbeta2 knock-out mice. Cardiovasc Res 2002;56:312–322.

    CAS  Google Scholar 

  53. Stalmans I, Lambrechts D, De Smet F, Jansen S, Wang J, Maity S, Kneer P, von der Ohe M, Swillen A, Maes C, Gewillig M, Molin DG, Hellings P, Boetel T, Haardt M, Compernolle V, Dewerchin M, Plaisance S, Vlietinck R, Emanuel B, Gittenberger-de Groot AC, Scambler P, Morrow B, Driscol DA, Moons L, Esguerra CV, Carmeliet G, Behn-Krappa A, Devriendt K, Collen D, Conway SJ, Carmeliet P. VEGF: a modifier of the del22q11 (DiGeorge) syndrome? Nat Med 2003;9:173–182.

    CAS  Google Scholar 

  54. Bao P, Kodra A, Tomic-Canic M, Golinko MS, Ehrlich HP, Brem H. The role of vascular endothelial growth factor in wound healing. J Surg Res (in press, 2008).

    Google Scholar 

  55. McGrath MH, Emery JM, 3rd. The effect of inhibition of angiogenesis in granulation tissue on wound healing and the fibroblast. Ann Plast Surg 1985;15:105–122.

    CAS  Google Scholar 

  56. Nissen NN, Polverini PJ, Koch AE, Volin MV, Gamelli RL, DiPietro LA. Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing. Am J Pathol 1998;152:1445–1452.

    CAS  Google Scholar 

  57. Gerber HP, Kowalski J, Sherman D, Eberhard DA, Ferrara N. Complete inhibition of rhabdomyosarcoma xenograft growth and neovascularization requires blockade of both tumor and host vascular endothelial growth factor. Cancer Res 2000;60:6253–6258.

    CAS  Google Scholar 

  58. Fukumura D, Xavier R, Sugiura T, Chen Y, Park EC, Lu N, Selig M, Nielsen G, Taksir T, Jain RK, Seed B. Tumor induction of VEGF promoter activity in stromal cells. Cell 1998;94:715–725.

    CAS  Google Scholar 

  59. Kishimoto J, Ehama R, Ge Y, Kobayashi T, Nishiyama T, Detmar M, Burgeson RE. In vivo detection of human vascular endothelial growth factor promoter activity in transgenic mouse skin. Am J Pathol 2000;157:103–110.

    CAS  Google Scholar 

  60. Tsuzuki Y, Fukumura D, Oosthuyse B, Koike C, Carmeliet P, Jain RK. Vascular endothelial growth factor (VEGF) modulation by targeting hypoxia-inducible factor-1alpha–> hypoxia response element–> VEGF cascade differentially regulates vascular response and growth rate in tumors. Cancer Res 2000;60:6248–6252.

    CAS  Google Scholar 

  61. Presta M, Dell’Era P, Mitola S, Moroni E, Ronca R, Rusnati M. Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev 2005;16:159–178.

    CAS  Google Scholar 

  62. Gross JL, Herblin WF, Dusak BA, Czerniak P, Diamond MD, Sun T, Eidsvoog K, Dexter DL, Yayon A. Effects of modulation of basic fibroblast growth factor on tumor growth in vivo. J Natl Cancer Inst 1993;85:121–131.

    Google Scholar 

  63. Colnot C. Cellular and molecular interactions regulating skeletogenesis. J Cell Biochem 2005;95:688–697.

    CAS  Google Scholar 

  64. Hall BK, Miyake T. All for one and one for all: condensations and the initiation of skeletal development. BioEssays 2000;22:138–147.

    CAS  Google Scholar 

  65. Colnot C, Lu C, Hu D, Helms JA. Distinguishing the contributions of the perichondrium, cartilage, and vascular endothelium to skeletal development. Dev Biol 2004;269:55–69.

    CAS  Google Scholar 

  66. Maes C, Carmeliet P, Moermans K, Stockmans I, Smets N, Collen D, Bouillon R, Carmeliet G. Impaired angiogenesis and endochondral bone formation in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188. Mech Dev 2002;111:61–73.

    CAS  Google Scholar 

  67. Engsig MT, Chen QJ, Vu TH, Pedersen AC, Therkidsen B, Lund LR, Henriksen K, Lenhard T, Foged NT, Werb Z, Delaisse JM. Matrix metalloproteinase 9 and vascular endothelial growth factor are essential for osteoclast recruitment into developing long bones. J Cell Biol 2000;151:879–889.

    CAS  Google Scholar 

  68. Urist MR. Bone: formation by autoinduction. 1965. Clin Orthop Relat Res 2002;(395):4–10.

    Google Scholar 

  69. Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors 2004;22:233–241.

    CAS  Google Scholar 

  70. Kroese-Deutman HC, Ruhe PQ, Spauwen PH, Jansen JA. Bone inductive properties of rhBMP-2 loaded porous calcium phosphate cement implants inserted at an ectopic site in rabbits. Biomaterials 2005;26:1131–1138.

    CAS  Google Scholar 

  71. Wang EA, Israel DI, Kelly S, Luxenberg DP. Bone morphogenetic protein-2 causes commitment and differentiation in C3H10T1/2 and 3T3 cells. Growth Factors 1993;9:57–71.

    CAS  Google Scholar 

  72. Asahina I, Sampath TK, Hauschka PV. Human osteogenic protein-1 induces chondroblastic, osteoblastic, and/or adipocytic differentiation of clonal murine target cells. Exp Cell Res 1996;222:38–47.

    CAS  Google Scholar 

  73. Cheng H, Jiang W, Phillips FM, Haydon RC, Peng Y, Zhou L, Luu HH, An N, Breyer B, Vanichakarn P, Szatkowski JP, Park JY, He TC. Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg Am 2003;85-A:1544–1552.

    Google Scholar 

  74. Giannoudis PV, Kanakaris NK, Einhorn TA. Interaction of bone morphogenetic proteins with cells of the osteoclast lineage: review of the existing evidence. Osteoporos Int 2007;18:1565–1581.

    CAS  Google Scholar 

  75. Wutzl A, Brozek W, Lernbass I, Rauner M, Hofbauer G, Schopper C, Watzinger F, Peterlik M, Pietschmann P. Bone morphogenetic proteins 5 and 6 stimulate osteoclast generation. J Biomed Mater Res A 2006;77:75–83.

    Google Scholar 

  76. Canalis E, Raisz LG. Effect of fibroblast growth factor on cultured fetal rat calvaria. Metabolism 1980;29:108–114.

    CAS  Google Scholar 

  77. Rodan SB, Wesolowski G, Thomas KA, Yoon K, Rodan GA. Effects of acidic and basic fibroblast growth factors on osteoblastic cells. Connect Tissue Res 1989;20:283–288.

    CAS  Google Scholar 

  78. Quarto N, Longaker MT. FGF-2 inhibits osteogenesis in mouse adipose tissue-derived stromal cells and sustains their proliferative and osteogenic potential state. Tissue Eng 2006;12:1405–1418.

    CAS  Google Scholar 

  79. McCarthy TL, Centrella M, Canalis E. Effects of fibroblast growth factors on deoxyribonucleic acid and collagen synthesis in rat parietal bone cells. Endocrinology 1989;125:2118–2126.

    CAS  Google Scholar 

  80. Kwan MD, Slater BJ, Wan DC, Longaker MT. Cell-based therapies for skeletal regenerative medicine. Hum Mol Genet 2008;17:R93–R98.

    CAS  Google Scholar 

  81. Lieberman JR, Daluiski A, Einhorn TA. The role of growth factors in the repair of bone. Biology and clinical applications. J Bone Joint Surg Am 2002;84-A:1032–1044.

    Google Scholar 

  82. Hughes FJ, Turner W, Belibasakis G, Martuscelli G. Effects of growth factors and cytokines on osteoblast differentiation. Periodontol 2000 2006;41:48–72.

    Google Scholar 

  83. Simpson AH, Mills L, Noble B. The role of growth factors and related agents in accelerating fracture healing. J Bone Joint Surg Br 2006;88:701–705.

    CAS  Google Scholar 

  84. Hadjidakis DJ, Androulakis II. Bone remodeling. Ann N Y Acad Sci 2006;1092:385–396.

    CAS  Google Scholar 

  85. Hu YY, Zhang C, Lu R, Xu JQ, Li D. Repair of radius defect with bone-morphogenetic-protein loaded hydroxyapatite/collagen-poly(l-lactic acid) composite. Chin J Traumatol 2003;6:67–74.

    CAS  Google Scholar 

  86. Conover CA. Insulin-like growth factor-binding proteins and bone metabolism. Am J Physiol Endocrinol Metab 2008;294:E10–E14.

    CAS  Google Scholar 

  87. Hoeflich A, Gotz W, Lichanska AM, Bielohuby M, Tonshoff B, Kiepe D. Effects of insulin-like growth factor binding proteins in bone – a matter of cell and site. Arch Physiol Biochem 2007;113:142–153.

    CAS  Google Scholar 

  88. Lynch SE, Buser D, Hernandez RA, Weber HP, Stich H, Fox CH, Williams RC. Effects of the platelet-derived growth factor/insulin-like growth factor-I combination on bone regeneration around titanium dental implants. Results of a pilot study in beagle dogs. J Periodontol 1991;62:710–716.

    CAS  Google Scholar 

  89. Raschke M, Wildemann B, Inden P, Bail H, Flyvbjerg A, Hoffmann J, Haas NP, Schmidmaier G. Insulin-like growth factor-1 and transforming growth factor-beta1 accelerates osteotomy healing using polylactide-coated implants as a delivery system: a biomechanical and histological study in minipigs. Bone 2002;30:144–151.

    CAS  Google Scholar 

  90. Takita H, Tsuruga E, Ono I, Kuboki Y. Enhancement by bFGF of osteogenesis induced by rhBMP-2 in rats. Eur J Oral Sci 1997;105:588–592.

    CAS  Google Scholar 

  91. Centrella M, McCarthy TL, Kusmik WF, Canalis E. Relative binding and biochemical effects of heterodimeric and homodimeric isoforms of platelet-derived growth factor in osteoblast-enriched cultures from fetal rat bone. J Cell Physiol 1991;147:420–426.

    CAS  Google Scholar 

  92. Fiedler J, Etzel N, Brenner RE. To go or not to go: migration of human mesenchymal progenitor cells stimulated by isoforms of PDGF. J Cell Biochem 2004;93:990–998.

    CAS  Google Scholar 

  93. Mehrotra M, Krane SM, Walters K, Pilbeam C. Differential regulation of platelet-derived growth factor stimulated migration and proliferation in osteoblastic cells. J Cell Biochem 2004;93:741–752.

    CAS  Google Scholar 

  94. Kanaan RA, Kanaan LA. Transforming growth factor beta1, bone connection. Med Sci Monit 2006;12:RA164–RA169.

    CAS  Google Scholar 

  95. Centrella M, Horowitz MC, Wozney JM, McCarthy TL. Transforming growth factor-beta gene family members and bone. Endocr Rev 1994;15:27–39.

    CAS  Google Scholar 

  96. Robey PG, Young MF, Flanders KC, Roche NS, Kondaiah P, Reddi AH, Termine JD, Sporn MB, Roberts AB. Osteoblasts synthesize and respond to transforming growth factor-type beta (TGF-beta) in vitro. J Cell Biol 1987;105:457–463.

    CAS  Google Scholar 

  97. Maeda S, Hayashi M, Komiya S, Imamura T, Miyazono K. Endogenous TGF-beta signaling suppresses maturation of osteoblastic mesenchymal cells. EMBO J 2004;23:552–563.

    CAS  Google Scholar 

  98. Lieb E, Vogel T, Milz S, Dauner M, Schulz MB. Effects of transforming growth factor beta1 on bonelike tissue formation in three-dimensional cell culture. II: Osteoblastic differentiation. Tissue Eng 2004;10:1414–1425.

    CAS  Google Scholar 

  99. Bodine PV, Billiard J, Moran RA, Ponce-de-Leon H, McLarney S, Mangine A, Scrimo MJ, Bhat RA, Stauffer B, Green J, Stein GS, Lian JB, Komm BS. The Wnt antagonist secreted frizzled-related protein-1 controls osteoblast and osteocyte apoptosis. J Cell Biochem 2005;96:1212–1230.

    CAS  Google Scholar 

  100. Anastassiades TP, Chopra RK, Wood A. Exogenous glycosaminoglycans (GAG) differentially modulate GAG synthesis by anchorage-independent cultures of the outer cells from neonatal rat calvaria in the absence and presence of TGF-beta. Mol Cell Biochem 1996;158:25–32.

    CAS  Google Scholar 

  101. Takeuchi Y, Matsumoto T, Ogata E, Shishiba Y. Effects of transforming growth factor beta 1 and L-ascorbate on synthesis and distribution of proteoglycans in murine osteoblast-like cells. J Bone Miner Res 1993;8:823–830.

    CAS  Google Scholar 

  102. Gerstenfeld LC, Cullinane DM, Barnes GL, Graves DT, Einhorn TA. Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation. J Cell Biochem 2003;88:873–884.

    CAS  Google Scholar 

  103. Katagiri T, Yamaguchi A, Komaki M, Abe E, Takahashi N, Ikeda T, Rosen V, Wozney JM, Fujisawa-Sehara A, Suda T. Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J Cell Biol 1994;127:1755–1766.

    CAS  Google Scholar 

  104. Bostrom MP. Expression of bone morphogenetic proteins in fracture healing. Clin Orthop Relat Res 1998;(355 Suppl):S116-S123.

    Google Scholar 

  105. Ishidou Y, Kitajima I, Obama H, Maruyama I, Murata F, Imamura T, Yamada N, ten Dijke P, Miyazono K, Sakou T. Enhanced expression of type I receptors for bone morphogenetic proteins during bone formation. |J Bone Miner Res 1995;10:1651–1659.

    CAS  Google Scholar 

  106. Bourque WT, Gross M, Hall BK. Expression of four growth factors during fracture repair. Int J Dev Biol 1993;37:573–579.

    CAS  Google Scholar 

  107. Andrew JG, Hoyland J, Freemont AJ, Marsh D. Insulinlike growth factor gene expression in human fracture callus. Calcif Tissue Int 1993;53:97–102.

    CAS  Google Scholar 

  108. Rydziel S, Shaikh S, Canalis E. Platelet-derived growth factor-AA and -BB (PDGF-AA and -BB) enhance the synthesis of PDGF-AA in bone cell cultures. Endocrinology 1994;134:2541–2546.

    CAS  Google Scholar 

  109. Andrew JG, Hoyland JA, Freemont AJ, Marsh DR. Platelet-derived growth factor expression in normally healing human fractures. Bone 1995;16:455–460.

    CAS  Google Scholar 

  110. Joyce ME, Jingushi S, Bolander ME. Transforming growth factor-beta in the regulation of fracture repair. Orthop Clin North Am 1990;21:199–209.

    CAS  Google Scholar 

  111. de Vernejoul MC. Sclerosing bone disorders. Best Pract Res Clin Rheumatol 2008;22:71–83.

    CAS  Google Scholar 

  112. Ornitz DM. FGF signaling in the developing endochondral skeleton. Cytokine Growth Factor Rev 2005;16:205–213.

    CAS  Google Scholar 

  113. Li B. Bone morphogenetic protein-Smad pathway as drug targets for osteoporosis and cancer therapy. Endocr Metab Immune Disord Drug Targets 2008;8:208–219.

    CAS  Google Scholar 

  114. Niu T, Rosen CJ. The insulin-like growth factor-I gene and osteoporosis: a critical appraisal. Gene 2005;361:38–56.

    CAS  Google Scholar 

  115. Langlois JA, Rosen CJ, Visser M, Hannan MT, Harris T, Wilson PW, Kiel DP. Association between insulin-like growth factor I and bone mineral density in older women and men: the Framingham Heart Study. J Clin Endocrinol Metab 1998;83:4257–4262.

    CAS  Google Scholar 

  116. Fromigue O, Modrowski D, Marie PJ. Growth factors and bone formation in osteoporosis: roles for fibroblast growth factor and transforming growth factor beta. Curr Pharm Des 2004;10:2593–2603.

    CAS  Google Scholar 

  117. Liang H, Pun S, Wronski TJ. Bone anabolic effects of basic fibroblast growth factor in ovariectomized rats. Endocrinology 1999;140:5780–5788.

    CAS  Google Scholar 

  118. Dunstan CR, Boyce R, Boyce BF, Garrett IR, Izbicka E, Burgess WH, Mundy GR. Systemic administration of acidic fibroblast growth factor (FGF-1) prevents bone loss and increases new bone formation in ovariectomized rats. J Bone Miner Res 1999;14:953–959.

    CAS  Google Scholar 

  119. Kuhl PR, Griffith-Cima LG. Tethered epidermal growth factor as a paradigm for growth factor-induced stimulation from the solid phase. Nat Med 1996;2:1022–1027.

    CAS  Google Scholar 

  120. Schuessele A, Mayr H, Tessmar J, Goepferich A. Enhanced bone morphogenetic protein-2 performance on hydroxyapatite ceramic surfaces. J Biomed Mater Res A 2008.

    Google Scholar 

  121. Koch S, Yao C, Grieb G, Prevel P, Noah EM, Steffens GC. Enhancing angiogenesis in collagen matrices by covalent incorporation of VEGF. J Mater Sci Mater Med 2006;17:735–741.

    CAS  Google Scholar 

  122. Zisch AH, Schenk U, Schense JC, Sakiyama-Elbert SE, Hubbell JA. Covalently conjugated VEGF–fibrin matrices for endothelialization. J Control Release 2001;72:101–113.

    CAS  Google Scholar 

  123. Zhang G, Suggs LJ. Matrices and scaffolds for drug delivery in vascular tissue engineering. Adv Drug Deliv Rev 2007;59:360–373.

    CAS  Google Scholar 

  124. Kano MR, Morishita Y, Iwata C, Iwasaka S, Watabe T, Ouchi Y, Miyazono K, Miyazawa K. VEGF-A and FGF-2 synergistically promote neoangiogenesis through enhancement of endogenous PDGF-B-PDGFRbeta signaling. J Cell Sci 2005;118:3759–3768.

    CAS  Google Scholar 

  125. Cao R, Brakenhielm E, Pawliuk R, Wariaro D, Post MJ, Wahlberg E, Leboulch P, Cao Y. Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2. Nat Med 2003;9:604–613.

    CAS  Google Scholar 

  126. Hao X, Silva EA, Mansson-Broberg A, Grinnemo KH, Siddiqui AJ, Dellgren G, Wardell E, Brodin LA, Mooney DJ, Sylven C. Angiogenic effects of sequential release of VEGF-A165 and PDGF-BB with alginate hydrogels after myocardial infarction. Cardiovasc Res 2007;75:178–185.

    CAS  Google Scholar 

  127. Rophael JA, Craft RO, Palmer JA, Hussey AJ, Thomas GP, Morrison WA, Penington AJ, Mitchell GM. Angiogenic growth factor synergism in a murine tissue engineering model of angiogenesis and adipogenesis. Am J Pathol 2007;171:2048–2057.

    CAS  Google Scholar 

  128. Lee KW, Yoon JJ, Lee JH, Kim SY, Jung HJ, Kim SJ, Joh JW, Lee HH, Lee DS, Lee SK. Sustained release of vascular endothelial growth factor from calcium-induced alginate hydrogels reinforced by heparin and chitosan. Transplant Proc 2004;36:2464–2465.

    CAS  Google Scholar 

  129. Ishihara M, Obara K, Ishizuka T, Fujita M, Sato M, Masuoka K, Saito Y, Yura H, Matsui T, Hattori H, Kikuchi M, Kurita A. Controlled release of fibroblast growth factors and heparin from photocrosslinked chitosan hydrogels and subsequent effect on in vivo vascularization. J Biomed Mater Res A 2003;64:551–559.

    Google Scholar 

  130. Zhu XH, Tabata Y, Wang CH, Tong YW. Delivery of basic fibroblast growth factor from gelatin microsphere scaffold for the growth of human umbilical vein endothelial cells. Tissue Eng Part A 2008;14:1939–1947.

    CAS  Google Scholar 

  131. Yao C, Prevel P, Koch S, Schenck P, Noah EM, Pallua N, Steffens G. Modification of collagen matrices for enhancing angiogenesis. Cells Tissues Organs 2004;178:189–196.

    CAS  Google Scholar 

  132. Schmidmaier G, Wildemann B, Lubberstedt M, Haas NP, Raschke M. IGF-I and TGF-beta 1 incorporated in a poly(D,L-lactide) implant coating stimulates osteoblast differentiation and collagen-1 production but reduces osteoblast proliferation in cell culture. J Biomed Mater Res B. Appl Biomater 2003;65:157–162.

    CAS  Google Scholar 

  133. Schmidmaier G, Wildemann B, Bail H, Lucke M, Fuchs T, Stemberger A, Flyvbjerg A, Haas NP, Raschke M. Local application of growth factors (insulin-like growth factor-1 and transforming growth factor-beta1) from a biodegradable poly(d,l-lactide) coating of osteosynthetic implants accelerates fracture healing in rats. Bone 2001;28:341–350.

    CAS  Google Scholar 

  134. Schmidmaier G, Wildemann B, Gabelein T, Heeger J, Kandziora F, Haas NP, Raschke M. Synergistic effect of IGF-I and TGF-beta1 on fracture healing in rats: single versus combined application of IGF-I and TGF-beta1. Acta Orthop Scand 2003;74:604–610.

    Google Scholar 

  135. Kandziora F, Pflugmacher R, Scholz M, Schafer J, Schollmeier G, Schmidmaier G, Duda G, Raschke M, Haas NP. Dose-dependent effects of combined IGF-I and TGF-beta1 application in a sheep cervical spine fusion model. Eur Spine J 2003;12:464–473.

    CAS  Google Scholar 

  136. Raiche AT, Puleo DA. Cell responses to BMP-2 and IGF-I released with different time-dependent profiles.J Biomed Mater Res A 2004;69:342–350.

    CAS  Google Scholar 

  137. Friess W, Uludag H, Foskett S, Biron R, Sargeant C. Characterization of absorbable collagen sponges as rhBMP-2 carriers. Int J Pharm 1999;187:91–99.

    CAS  Google Scholar 

  138. Geiger M, Li RH, Friess W. Collagen sponges for bone regeneration with rhBMP-2. Adv Drug Deliv Rev 2003;55:1613–1629.

    CAS  Google Scholar 

  139. Murakami N, Saito N, Takahashi J, Ota H, Horiuchi H, Nawata M, Okada T, Nozaki K, Takaoka K. Repair of a proximal femoral bone defect in dogs using a porous surfaced prosthesis in combination with recombinant BMP-2 and a synthetic polymer carrier. Biomaterials 2003;24:2153–2159.

    CAS  Google Scholar 

  140. Kaito T, Myoui A, Takaoka K, Saito N, Nishikawa M, Tamai N, Ohgushi H, Yoshikawa H. Potentiation of the activity of bone morphogenetic protein-2 in bone regeneration by a PLA-PEG/hydroxyapatite composite. Biomaterials 2005;26:73–79.

    CAS  Google Scholar 

  141. Wikesjo UM, Lim WH, Thomson RC, Cook AD, Wozney JM, Hardwick WR. Periodontal repair in dogs: evaluation of a bioabsorbable space-providing macroporous membrane with recombinant human bone morphogenetic protein-2. J Periodontol 2003;74:635–647.

    CAS  Google Scholar 

  142. Mayer M, Hollinger J, Ron E, Wozney J. Maxillary alveolar cleft repair in dogs using recombinant human bone morphogenetic protein-2 and a polymer carrier. Plast Reconstr Surg 1996;98:247–259.

    CAS  Google Scholar 

  143. PC, Chang BY, Liu CM. Liu 2004: Bone tissue engineering with novel rhBMP-2-PLLA composite scaffolds. Journal of Biomedical Research A 771–780.

    Google Scholar 

  144. Mabilleau G, Aguado E, Stancu IC, Cincu C, Basle MF, Chappard D. Effects of FGF-2 release from a hydrogel polymer on bone mass and microarchitecture. Biomaterials 2008;29:1593–1600.

    CAS  Google Scholar 

  145. Woo BH, Fink BF, Page R, Schrier JA, Jo YW, Jiang G, DeLuca M, Vasconez HC, DeLuca PP. Enhancement of bone growth by sustained delivery of recombinant human bone morphogenetic protein-2 in a polymeric matrix. Pharm Res 2001;18:1747–1753.

    CAS  Google Scholar 

  146. Ripamonti U, Crooks J, Rueger DC. Induction of bone formation by recombinant human osteogenic protein-1 and sintered porous hydroxyapatite in adult primates. Plast Reconstr Surg 2001;107:977–988.

    CAS  Google Scholar 

  147. Kim SJ, Kim SY, Kwon CH, Kim YK. Differential effect of FGF and PDGF on cell proliferation and migration in osteoblastic cells. Growth Factors 2007;25:77–86.

    CAS  Google Scholar 

  148. Ten Dijke P. Bone morphogenetic protein signal transduction in bone. Curr Med Res Opin 2006;22 Suppl 1:S7–S11.

    CAS  Google Scholar 

  149. Puleo D. Biotherapeutics in orthopaedic medicine: accelerating the healing process? BioDrugs 2003;17:301–314.

    CAS  Google Scholar 

  150. Ehrbar M, Djonov VG, Schnell C, Tschanz SA, Martiny-Baron G, Schenk U, Wood J, Burri PH, Hubbell JA, Zisch AH. Cell-demanded liberation of VEGF121 from fibrin implants induces local and controlled blood vessel growth. Circ Res 2004;94:1124–1132.

    CAS  Google Scholar 

  151. Ehrbar M, Metters A, Zammaretti P, Hubbell JA, Zisch AH. Endothelial cell proliferation and progenitor maturation by fibrin-bound VEGF variants with differential susceptibilities to local cellular activity. J Control Release 2005;101:93–109.

    CAS  Google Scholar 

  152. Gautschi OP, Frey SP, Zellweger R. Bone morphogenetic proteins in clinical applications. ANZ J Surg 2007;77:626–631.

    Google Scholar 

  153. Hollinger JO, Schmitt JM, Buck DC, Shannon R, Joh SP, Zegzula HD, Wozney J. Recombinant human bone morphogenetic protein-2 and collagen for bone regeneration. J Biomed Mater Res 1998;43:356–364.

    CAS  Google Scholar 

  154. Giannobile WV, Finkelman RD, Lynch SE. Comparison of canine and non-human primate animal models for periodontal regenerative therapy: results following a single administration of PDGF/IGF-I. J Periodontol 1994;65:1158–1168.

    CAS  Google Scholar 

  155. Howell TH, Fiorellini JP, Paquette DW, Offenbacher S, Giannobile WV, Lynch SE. A phase I/II clinical trial to evaluate a combination of recombinant human platelet-derived growth factor-BB and recombinant human insulin-like growth factor-I in patients with periodontal disease. J Periodontol 1997;68:1186–1193.

    CAS  Google Scholar 

  156. Wildemann B, Lubberstedt M, Haas NP, Raschke M, Schmidmaier G. IGF-I and TGF-beta 1 incorporated in a poly(d,l-lactide) implant coating maintain their activity over long-term storage-cell culture studies on primary human osteoblast-like cells. Biomaterials 2004;25:3639–3644.

    CAS  Google Scholar 

  157. Ripamonti U, Duneas N, Van Den Heever B, Bosch C, Crooks J. Recombinant transforming growth factor-beta1 induces endochondral bone in the baboon and synergizes with recombinant osteogenic protein-1 (bone morphogenetic protein-7) to initiate rapid bone formation. J Bone Miner Res 1997;12:1584–1595.

    CAS  Google Scholar 

  158. Simmons CA, Alsberg E, Hsiong S, Kim WJ, Mooney DJ. Dual growth factor delivery and controlled scaffold degradation enhance in vivo bone formation by transplanted bone marrow stromal cells. Bone 2004;35:562–569.

    CAS  Google Scholar 

  159. Marden LJ, Fan RS, Pierce GF, Reddi AH, Hollinger JO. Platelet-derived growth factor inhibits bone regeneration induced by osteogenin, a bone morphogenetic protein, in rat craniotomy defects. J Clin Invest 1993;92:2897–2905.

    CAS  Google Scholar 

  160. Ley CD, Olsen MW, Lund EL, Kristjansen PE. Angiogenic synergy of bFGF and VEGF is antagonized by Angiopoietin-2 in a modified in vivo Matrigel assay. Microvasc Res 2004;68:161–168.

    CAS  Google Scholar 

  161. Richardson TP, Peters MC, Ennett AB, Mooney DJ. Polymeric system for dual growth factor delivery. Nat Biotechnol 2001;19:1029–1034.

    CAS  Google Scholar 

  162. Huang YC, Kaigler D, Rice KG, Krebsbach PH, Mooney DJ. Combined angiogenic and osteogenic factor delivery enhances bone marrow stromal cell-driven bone regeneration. J Bone Miner Res 2005;20:848–857.

    CAS  Google Scholar 

  163. Kanczler JM, Oreffo RO. Osteogenesis and angiogenesis: the potential for engineering bone. Eur Cell Mater 2008;15:100–114.

    CAS  Google Scholar 

  164. Huang W, Carlsen B, Wulur I, Rudkin G, Ishida K, Wu B, Yamaguchi DT, Miller TA. BMP-2 exerts differential effects on differentiation of rabbit bone marrow stromal cells grown in two-dimensional and three-dimensional systems and is required for in vitro bone formation in a PLGA scaffold. Exp Cell Res 2004;299:325–334.

    CAS  Google Scholar 

  165. Dai J, Rabie AB. VEGF: an essential mediator of both angiogenesis and endochondral ossification. J Dent Res 2007;86:937–950.

    CAS  Google Scholar 

  166. Patel ZS, Young S, Tabata Y, Jansen JA, Wong ME, Mikos AG. Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model. Bone 2008;43:931–940.

    CAS  Google Scholar 

  167. Raiche AT, Puleo DA. In vitro effects of combined and sequential delivery of two bone growth factors. Biomaterials 2004;25:677–685.

    CAS  Google Scholar 

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  1. Department of Biomedical Engineering, The University of Texas at San Antonio, San Antonio, TX, 78249, USA

    Christopher C. Gibson & David A. Puleo

  2. Center for Biomedical Engineering, University of Kentucky, Lexington, KY, 40506, USA

    Rena Bizios

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    Gibson, C.C., Puleo, D.A., Bizios, R. (2009). Cell and Tissue Interactions with Materials: The Role of Growth Factors. In: Puleo, D., Bizios, R. (eds) Biological Interactions on Materials Surfaces. Springer, New York, NY. https://doi.org/10.1007/978-0-387-98161-1_10

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