Growth factor-eluting technologies for bone tissue engineering

Drug Delivery and Translational Research

Volumn 6, Issue 2, 2016, Pages 184-194

  Nyberg, Ethan ^a   Holmes, Christina ^b   Witham, Timothy ^b   Grayson, Warren L ^a,c  

^a Johns Hopkins University   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

Biomaterials; Bone scaffold; Osteogenesis; Stem cells; Tissue engineering

Indexed keywords

GROWTH FACTOR; MOLECULAR SCAFFOLD; POLYELECTROLYTE; BIOMATERIAL; SIGNAL PEPTIDE;

ADSORPTION; ARTICLE; BIOMIMETICS; BIOMINERALIZATION; BONE DEVELOPMENT; BONE REGENERATION; BONE TISSUE; COVALENT BOND; FRACTURE HEALING; HYDROGEL; NANOENCAPSULATION; NANOTECHNOLOGY; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; SURFACE PROPERTY; TISSUE ENGINEERING; ANIMAL; CHEMISTRY; DRUG DELIVERY SYSTEM; DRUG EFFECTS; HUMAN; PROCEDURES; TISSUE SCAFFOLD;

ANIMALS; BIOCOMPATIBLE MATERIALS; BONE REGENERATION; DRUG DELIVERY SYSTEMS; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; OSTEOGENESIS; TISSUE ENGINEERING; TISSUE SCAFFOLDS;

EID: 84960121182     PISSN: 2190393X     EISSN: 21903948     Source Type: Journal    
DOI: 10.1007/s13346-015-0233-3     Document Type: Article

References (112)

1. O’Keefe RJ, Mao J. Bone tissue engineering and regeneration: from discovery to the clinic—an overview. Tissue Eng Part B. 2011;17:389–92. doi:10.1089/ten.TEB.2011.0475.
2. Khan SN, Cammisa FP, Sandhu HS, et al. The biology of bone grafting. J Am Acad Orthop Surg. 2005;1:77–86.
3. Luginbuehl V, Zoidis E, Meinel L, et al. Impact of IGF-I release kinetics on bone healing: a preliminary study in sheep. Eur J Pharm Biopharm. 2013;85:99–106. doi:10.1016/j.ejpb.2013.03.004.
4. Chen G, Deng C, Li Y-P. TGF-β and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci. 2012;8:272–88. doi:10.7150/ijbs.2929.
5. Schipani E, Maes C, Carmeliet G, Semenza GL. Regulation of osteogenesis-angiogenesis coupling by HIFs and VEGF. J Bone Miner Res. 2009;24:1347–53. doi:10.1359/jbmr.090602.
6. Mckibbin B. The biology of fracture healing in long bones. J Bone Joint Surg. 1978;60-B:150–62.
7. Caplan AI, Correa D. PDGF in bone formation and regeneration: new insights into a novel mechanism involving MSCs. J Orthop Res. 2011;29:1795–803. doi:10.1002/jor.21462.
8. Marie PJ, Miraoui H, Sévère N. FGF/FGFR signaling in bone formation: progress and perspectives. Growth Factors. 2012;30:117–23. doi:10.3109/08977194.2012.656761.
9. Yilgor P, Tuzlakoglu K, Reis RL, et al. Incorporation of a sequential BMP-2/BMP-7 delivery system into chitosan-based scaffolds for bone tissue engineering. Biomaterials. 2009;30:3551–9. doi:10.1016/j.biomaterials.2009.03.024.
10. Urist M. Bone: formation by autoinduction. Science. 1965;150:893–9.
11. Kisiel M, Martino MM, Ventura M, et al. Improving the osteogenic potential of BMP-2 with hyaluronic acid hydrogel modified with integrin-specific fibronectin fragment. Biomaterials. 2013;34:704–12. doi:10.1016/j.biomaterials.2012.10.015.
12. Rahman C, Ben-David D, Dhillon A, et al. Controlled release of BMP-2 from a sintered polymer scaffold enhances bone repair in a mouse calvarial defect model. J Tissue Eng Regen Med. 2014;8:59–66. doi:10.1002/term.
13. Yazici C, Takahata M, Reynolds DG, et al. Self-complementary AAV2.5-BMP2-coated femoral allografts mediated superior bone healing versus live autografts in mice with equivalent biomechanics to unfractured femur. Mol Ther. 2011;19:1416–25. doi:10.1038/mt.2010.294.
14. Bessa PC, Casal M, Reis RL. Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic, part II (BMP delivery). J. Tissue Eng. Regen. Med. 2008;2:81–96. doi:10.1002/term74
15. Ebara S, Nakayama K. Mechanism for the action of bone morphogenetic proteins and regulation of their activity. Spine (Phila Pa 1976). 2002;27:10–5. doi:10.1097/01.BRS.0000020727.98493.20.
16. Silva EA, Mooney DJ. Effects of VEGF temporal and spatial presentation on angiogenesis. Biomaterials. 2010;31:1235–41. doi:10.1016/j.biomaterials.2009.10.052.
17. Lenze U, Pohlig F, Seitz S, et al. Influence of osteogenic stimulation and VEGF treatment on in vivo bone formation in hMSC-seeded cancellous bone scaffolds. BMC Musculoskelet Disord. 2014;15:350. doi:10.1186/1471-2474-15-350.
18. Gabhann F, Mac JJW, Popel AS. VEGF gradients, receptor activation, and sprout guidance in resting and exercising skeletal muscle. J Appl Physiol. 2007;102:722–34. doi:10.1152/japplphysiol.00800.2006.
19. Kaigler D, Wang Z, Horger K, et al. VEGF scaffolds enhance angiogenesis and bone regeneration in irradiated osseous defects. J Bone Miner Res. 2006;21:735–44. doi:10.1359/jbmr.060120.
20. Ferrara N, Gerber H-P, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–76. doi:10.1038/nm0603-669.
21. Hutton DL, Moore EM, Gimble JM, Grayson WL. Platelet-derived growth factor and spatiotemporal cues induce development of vascularized bone tissue by adipose-derived stem cells. Tissue Eng Part A. 2013;19:2076–86. doi:10.1089/ten.TEA.2012.0752.
22. Amos PJ, Mulvey CL, Seaman SA, et al. Hypoxic culture and in vivo inflammatory environments affect the assumption of pericyte characteristics by human adipose and bone marrow progenitor cells. AJP Cell Physiol. 2011;301:C1378–88. doi:10.1152/ajpcell.00460.2010.
23. Clark RAF. Synergistic signaling from extracellular matrix-growth factor complexes. J Invest Dermatol. 2008;128:1354–5. doi:10.1038/jid.2008.75.
24. Dyondi D, Webster TJ, Banerjee R. A nanoparticulate injectable hydrogel as a tissue engineering scaffold for multiple growth factor delivery for bone regeneration. Int J Nanomedicine. 2012;8:47–59. doi:10.2147/IJN.S37953.
25. Takechi M, Tatehara S, Satomura K, et al. Effect of FGF-2 and melatonin on implant bone healing: a histomorphometric study. J Mater Sci Mater Med. 2008;19:2949–52. doi:10.1007/s10856-008-3416-3.
26. Aspenberg P, Lohmander LS. Fibroblast growth factor stimulates bone formation bone induction studied in rats. Acta Orthop. 1989;60:473–6. doi:10.3109/17453678909149323.
27. Kang H, Sung J, Jung H-M, et al. Insulin-like growth factor 2 promotes osteogenic cell differentiation in the parthenogenetic murine embryonic stem cells. Tissue Eng Part A. 2012;18:331–41. doi:10.1089/ten.TEA.2011.0074.
28. Srouji S, Rachmiel A, Blumenfeld I, Livne E. Mandibular defect repair by TGF-beta and IGF-1 released from a biodegradable osteoconductive hydrogel. J Craniomaxillofac Surg. 2005;33:79–84. doi:10.1016/j.jcms.2004.09.003.
29. Xian L, Wu X, Pang L, et al. Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cells. Nat Med. 2012;18:1095–101. doi:10.1038/nm.2793.
30. Crane JL, Cao X. Function of matrix IGF-1 in coupling bone resorption and formation. J Mol Med (Berl). 2014;92:107–15. doi:10.1007/s00109-013-1084-3.
31. Lin C-Y, Chang Y-H, Li K-C, et al. The use of ASCs engineered to express BMP2 or TGF-β3 within scaffold constructs to promote calvarial bone repair. Biomaterials. 2013;34:9401–12. doi:10.1016/j.biomaterials.2013.08.051.
32. Kleinheinz J, Jung S, Wermker K, et al. Release kinetics of VEGF165 from a collagen matrix and structural matrix changes in a circulation model. Head Face Med. 2010;6:17. doi:10.1186/1746-160X-6-17.
33. Ruhé PQ, Boerman OC, Russel FGM, et al. In vivo release of rhBMP-2 loaded porous calcium phosphate cement pretreated with albumin. J Mater Sci Mater Med. 2006;17:919–27. doi:10.1007/s10856-006-0181-z.
34. Malafaya PB, Silva GA, Reis RL. Natural-origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications. Adv Drug Deliv Rev. 2007;59:207–33. doi:10.1016/j.addr.2007.03.012.
35. Gunatillake PA, Adhikari R, Gadegaard N. Biodegradable synthetic polymers for tissue engineering. Eur Cells Mater. 2003;5:1–16.
36. Tessmar JK, Göpferich AM. Matrices and scaffolds for protein delivery in tissue engineering. Adv Drug Deliv Rev. 2007;59:274–91. doi:10.1016/j.addr.2007.03.020.
37. Raiche A, Puleo D. In vitro effects of combined and sequential delivery of two bone growth factors. Biomaterials. 2004;25:677–85. doi:10.1016/S0142-9612(03)00564-7.
38. Geuze RE, Theyse LFH, Kempen DHR, et al. A differential effect of bone morphogenetic protein-2 and vascular endothelial growth factor release timing on osteogenesis at ectopic and orthotopic sites in a large-animal model. Tissue Eng Part A. 2012;18:2052–62. doi:10.1089/ten.TEA.2011.0560.
39. Uludag H, D’Augusta D, Golden J, et al. Implantation of recombinant human bone morphogenetic proteins with biomaterial carriers: a correlation between protein pharmacokinetics and osteoinduction in the rat ectopic model. J Biomed Mater Res. 2000;50:227–38.
40. Brown KV, Li B, Guda T, et al. Improving bone formation in a rat femur segmental defect by controlling bone morphogenetic protein-2 release. Tissue Eng Part A. 2011;17:1735–46. doi:10.1089/ten.TEA.2010.0446.
41. Shields LBE, Raque GH, Glassman SD, et al. Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion. Spine (Phila Pa 1976). 2006;31:542–7. doi:10.1097/01.brs.0000201424.27509.72.
42. Cahill KS, Chi JH, Day A, Claus EB. Prevalence, complications, and hospital charges associated with use of bone-morphogenetic proteins in spinal fusion procedures. JAMA. 2009;302:58–66. doi:10.1001/jama.2009.956.
43. Border WA, Ruoslahti E. Transforming growth factor-beta in disease: the dark side of tissue repair. J Clin Invest. 1992;90:1–7. doi:10.1172/JCI115821.
44. Saltzman WM. Growth-factor delivery in tissue engineering. MRS Bull. 1996;21:62–5.
45. Zieris A, Prokoph S, Levental KR, et al. FGF-2 and VEGF functionalization of starPEG-heparin hydrogels to modulate biomolecular and physical cues of angiogenesis. Biomaterials. 2010;31:7985–94. doi:10.1016/j.biomaterials.2010.07.021.
46. Lopac SK, Torres MP, Wilson-Welder JH, et al. Effect of polymer chemistry and fabrication method on protein release and stability from polyanhydride microspheres. J Biomed Mater Res B Appl Biomater. 2009;91:938–47. doi:10.1002/jbm.b.31478.
47. Madurantakam PA, Rodriguez IA, Beckman MJ, et al. Evaluation of biological activity of bone morphogenetic proteins on exposure to commonly used electrospinning solvents. J Bioact Compat Polym. 2011;26:578–89. doi:10.1177/0883911511424012.
48. Determan AS, Wilson JH, Kipper MJ, et al. Protein stability in the presence of polymer degradation products: consequences for controlled release formulations. Biomaterials. 2006;27:3312–20. doi:10.1016/j.biomaterials.2006.01.054.
49. Jeon O, Song SJ, Kang S-W, et al. Enhancement of ectopic bone formation by bone morphogenetic protein-2 released from a heparin-conjugated poly(L-lactic-co-glycolic acid) scaffold. Biomaterials. 2007;28:2763–71. doi:10.1016/j.biomaterials.2007.02.023.
50. Zhao B, Katagiri T, Toyoda H, et al. Heparin potentiates the in Vivo ectopic bone formation induced by bone morphogenetic protein-2. J Biol Chem. 2006;281:23246–53. doi:10.1074/jbc.M511039200.
51. Bhang SH, Ph D, Jeon J. Heparin-conjugated fibrin as an injectable system. Tissue Eng Part A. 2010;16:1–10.
52. Whang K, Goldstick TK, Healy KE. A biodegradable polymer scaffold for delivery of osteotropic factors. Biomaterials. 2000;21:2545–51.
53. Nam YS, Yoon JJ, Park TG. A novel fabrication method of macroporous biodegradable polymer scaffolds using gas foaming salt as a porogen additive. J Biomed Mater Res. 2000;53:1–7.
54. Schliephake H, Weich HA, Schulz J, Gruber R. In vitro characterization of a slow release system of polylactic acid and rhBMP2. J Biomed Mater Res A. 2007;83:455–62. doi:10.1002/jbm.a.31227.
55. Gruber R, Weich HA, Dullin C, Schliephake H. Ectopic bone formation after implantation of a slow release system of polylactic acid and rhBMP-2. Clin Oral Implants Res. 2009;20:24–30. doi:10.1111/j.1600-0501.2008.01613.x.
56. Srouji S, Ben-David D, Lotan R, et al. 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. 2011;17:269–77. doi:10.1089/ten.TEA.2010.0250.
57. Fu Y-C, Nie H, Ho M-L, et al. Optimized bone regeneration based on sustained release from three-dimensional fibrous PLGA/HAp composite scaffolds loaded with BMP-2. Biotechnol Bioeng. 2008;99:996–1006. doi:10.1002/bit.21648.
58. Kim B-R, Nguyen TBL, Min Y-K, Lee B-T. In vitro and in vivo studies of BMP-2-loaded PCL-gelatin-BCP electrospun scaffolds. Tissue Eng Part A. 2014;20:3279–89. doi:10.1089/ten.TEA.2014.0081.
59. Schofer MD, Roessler PP, Schaefer J, et al. Electrospun PLLA nanofiber scaffolds and their use in combination with BMP-2 for reconstruction of bone defects. PLoS One. 2011;6, e25462. doi:10.1371/journal.pone.0025462.
60. Li C, Vepari C, Jin H-J, et al. Electrospun silk-BMP-2 scaffolds for bone tissue engineering. Biomaterials. 2006;27:3115–24. doi:10.1016/j.biomaterials.2006.01.022.
61. Kim S-H, Turnbull J, Guimond S. Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor. J Endocrinol. 2011;209:139–51. doi:10.1530/JOE-10-0377.
62. Ruppert R, Hoffmann E, Sebald W. Human bone morphogenetic protein 2 contains a heparin-binding site which modifies its biological activity. Eur J Biochem. 1996;237:295–302.
63. Rider CC. Heparin/heparan sulphate binding in the TGF-beta cytokine superfamily. Biochem Soc Trans. 2006;34:458–60. doi:10.1042/BST0340458.
64. Bhakta G, Rai B, Lim ZXH, et al. Hyaluronic acid-based hydrogels functionalized with heparin that support controlled release of bioactive BMP-2. Biomaterials. 2012;33:6113–22. doi:10.1016/j.biomaterials.2012.05.030.
65. Martino MM, Hubbell JA. The 12th-14th type III repeats of fibronectin function as a highly promiscuous growth factor-binding domain. FASEB J. 2010;24:4711–21. doi:10.1096/fj.09-151282.
66. Martino MM, Tortelli F, Mochizuki M, et al. Engineering the growth factor microenvironment with fibronectin domains to promote wound and bone tissue healing. Sci Transl Med. 2011;3:100ra89. doi:10.1126/scitranslmed.3002614.
67. Hamilton PT, Jansen MS, Ganesan S, et al. Improved bone morphogenetic protein-2 retention in an injectable collagen matrix using bifunctional peptides. PLoS One. 2013;8:e70715. doi:10.1371/journal.pone.0070715.
68. Haynes CA, Norde W. Globular proteins at solid/liquid interfaces. Colloids Surf B Biointerfaces. 1994;2:517–66. doi:10.1016/0927-7765(94)80066-9.
69. King WJ, Krebsbach PH. Growth factor delivery: how surface interactions modulate release in vitro and in vivo. Adv Drug Deliv Rev. 2012;64:1239–56. doi:10.1016/j.addr.2012.03.004.
70. De Geest BG, Sanders NN, Sukhorukov GB, et al. Release mechanisms for polyelectrolyte capsules. Chem Soc Rev. 2007;36:636–49. doi:10.1039/b600460c.
71. Decher G, Hong JD, Schmitt J. Buildup of ultrathin multilayer films by a self-assembly process: III. Consecutively alternating adsorption of anionic and cationic polyelectrolytes on charged surfaces. Thin Solid Films. 1992;210–211:831–5. doi:10.1016/0040-6090(92)90417-A.
72. Benkirane-Jessel N, Lavalle P, Hübsch E, et al. Short-time tuning of the biological activity of functionalized polyelectrolyte multilayers. Adv Funct Mater. 2005;15:648–54. doi:10.1002/adfm.200400129.
73. Jessel N, Oulad-Abdelghani M, Meyer F, et al. Multiple and time-scheduled in situ DNA delivery mediated by beta-cyclodextrin embedded in a polyelectrolyte multilayer. Proc Natl Acad Sci U S A. 2006;103:8618–21. doi:10.1073/pnas.0508246103.
74. Lvov Y, Ariga K, Ichinose I, Kunitake T. Assembly of multicomponent protein films by means of electrostatic layer-by-layer adsorption. J Am Chem Soc. 1995;117:6117–23. doi:10.1021/ja00127a026.
75. Holmes C, Daoud J, Bagnaninchi PO, Tabrizian M. Polyelectrolyte multilayer coating of 3D scaffolds enhances tissue growth and gene delivery: non-invasive and label-free assessment. Adv Healthcare Mater. 2014;3:572–80. doi:10.1002/adhm.201300301.
76. Macdonald ML, Samuel RE, Shah NJ, et al. Tissue integration of growth factor-eluting layer-by-layer polyelectrolyte multilayer coated implants. Biomaterials. 2011;32:1446–53. doi:10.1016/j.biomaterials.2010.10.052.
77. Sakai S, Yamada Y, Yamaguchi T, et al. Surface immobilization of poly(ethyleneimine) and plasmid DNA on electrospun poly(L-lactic acid) fibrous mats using a layer-by-layer approach for gene delivery. J Biomed Mater Res A. 2009;88:281–7. doi:10.1002/jbm.a.31870.
78. Yu X, Khalil A, Dang PN, et al. Multilayered inorganic microparticles for tunable dual growth factor delivery. Adv Funct Mater. 2014;24:3082–93. doi:10.1002/adfm.201302859.
79. Xu X, Jha AK, Duncan RL, Jia X. Heparin-decorated, hyaluronic acid-based hydrogel particles for the controlled release of bone morphogenetic protein 2. Acta Biomater. 2011;7:3050–9. doi:10.1016/j.actbio.2011.04.018.
80. Luz GM, Boesel L, del Campo A, Mano JF. Micropatterning of bioactive glass nanoparticles on chitosan membranes for spatial controlled biomineralization. Langmuir. 2012;28:6970–7. doi:10.1021/la300667g.
81. Park J, Lutz R, Felszeghy E, et al. The effect on bone regeneration of a liposomal vector to deliver BMP-2 gene to bone grafts in peri-implant bone defects. Biomaterials. 2007;28:2772–82. doi:10.1016/j.biomaterials.2007.02.009.
82. Sheyn D, Kallai I, Tawackoli W, et al. Gene-modified adult stem cells regenerate vertebral bone defect in a rat model. Mol Pharm. 2011;8:1592–601. doi:10.1021/mp200226c.
83. Li Y, Fan L, Liu S, et al. The promotion of bone regeneration through positive regulation of angiogenic-osteogenic coupling using microRNA-26a. Biomaterials. 2013;34:5048–58. doi:10.1016/j.biomaterials.2013.03.052.
84. Ishihara A, Zekas LJ, Litsky AS, et al. Dermal fibroblast-mediated BMP2 therapy to accelerate bone healing in an equine osteotomy model. J Orthop Res. 2010;28:403–11. doi:10.1002/jor.20978.
85. Elangovan S, D’Mello SR, Hong L, et al. The enhancement of bone regeneration by gene activated matrix encoding for platelet derived growth factor. Biomaterials. 2014;35:737–47. doi:10.1016/j.biomaterials.2013.10.021.
86. Kretlow JD, Mikos AG. Review: mineralization of synthetic polymer scaffolds for bone tissue engineering. Tissue Eng. 2007;13:927–38. doi:10.1089/ten.2006.0394.
87. Kokubo T, Ito S, Huang ZT, et al. Ca, P-rich layer formed on high-strength bioactive glass-ceramic A-W. J Biomed Mater Res. 1990;24:331–43. doi:10.1002/jbm.820240306.
88. Barrère F, van der Valk CM, Meijer G, et al. Osteointegration of biomimetic apatite coating applied onto dense and porous metal implants in femurs of goats. J Biomed Mater Res B Appl Biomater. 2003;67:655–65. doi:10.1002/jbm.b.10057.
89. Park S-B, Hasegawa U, van der Vlies AJ, et al. Preparation of poly(γ-glutamic acid)/hydroxyapatite monolith via biomineralization for bone tissue engineering. J Biomater Sci Polym Ed. 2014;25:1875–90. doi:10.1080/09205063.2014.953404.
90. Davis HE, Case EM, Miller SL, et al. Osteogenic response to BMP-2 of hMSCs grown on apatite-coated scaffolds. Biotechnol Bioeng. 2011;108:2727–35. doi:10.1002/bit.23227.
91. Deplaine H, Lebourg M, Ripalda P, et al. Biomimetic hydroxyapatite coating on pore walls improves osteointegration of poly(L-lactic acid) scaffolds. J Biomed Mater Res B Appl Biomater. 2013;101:173–86. doi:10.1002/jbm.b.32831.
92. Liu Y, de Groot K, Hunziker EB. BMP-2 liberated from biomimetic implant coatings induces and sustains direct ossification in an ectopic rat model. Bone. 2005;36:745–57. doi:10.1016/j.bone.2005.02.005.
93. Liu Y, Hunziker EB, Layrolle P, et al. Bone morphogenetic protein 2 incorporated into biomimetic coatings retains its biological activity. Tissue Eng. 2004;10:101–8. doi:10.1089/107632704322791745.
94. Szentivanyi A, Chakradeo T, Zernetsch H, Glasmacher B. Electrospun cellular microenvironments: understanding controlled release and scaffold structure. Adv Drug Deliv Rev. 2011;63:209–20. doi:10.1016/j.addr.2010.12.002.
95. Bajpai AK, Shukla SK, Bhanu S, Kankane S. Responsive polymers in controlled drug delivery. Prog Polym Sci. 2008;33:1088–118. doi:10.1016/j.progpolymsci.2008.07.005.
96. Holloway JL, Ma H, Rai R, Burdick JA. Modulating hydrogel crosslink density and degradation to control bone morphogenetic protein delivery and in vivo bone formation. J Control Release. 2014;191:63–70. doi:10.1016/j.jconrel.2014.05.053.
97. He X, Ma J, Jabbari E. Effect of grafting RGD and BMP-2 protein-derived peptides to a hydrogel substrate on osteogenic differentiation of marrow stromal cells. Langmuir. 2008;24:12508–16. doi:10.1021/la802447v.
98. Patel N, Padera R, Sanders GH, et al. Spatially controlled cell engineering on biodegradable polymer surfaces. FASEB J. 1998;12:1447–54.
99. Segura T, Chung PH, Shea LD. DNA delivery from hyaluronic acid-collagen hydrogels via a substrate-mediated approach. Biomaterials. 2005;26:1575–84. doi:10.1016/j.biomaterials.2004.05.007.
100. Zhang H, Migneco F, Lin C-Y, Hollister SJ. Chemically-conjugated bone morphogenetic protein-2 on three-dimensional polycaprolactone scaffolds stimulates osteogenic activity in bone marrow stromal cells. Tissue Eng Part A. 2010;16:3441–8. doi:10.1089/ten.TEA.2010.0132.
101. Shah NJ, Hyder MN, Quadir MA, et al. Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction. Proc Natl Acad Sci U S A. 2014;111:12847–52. doi:10.1073/pnas.1408035111.
102. Sant S, Hancock MJ, Donnelly JP, et al. Biomimetic gradient hydrogels for tissue engineering. Can J Chem Eng. 2010;88:899–911. doi:10.1002/cjce.20411.
103. Kapur TA, Shoichet MS. Immobilized concentration gradients of nerve growth factor guide neurite outgrowth. J Biomed Mater Res A. 2004;68:235–43. doi:10.1002/jbm.a.10168.
104. De Long SA, Gobin AS, West JL. Covalent immobilization of RGDS on hydrogel surfaces to direct cell alignment and migration. J Control Release. 2005;109:139–48. doi:10.1016/j.jconrel.2005.09.020.
105. Chen RR, Silva EA, Yuen WW, Mooney DJ. Spatio-temporal VEGF and PDGF delivery patterns blood vessel formation and maturation. Pharm Res. 2007;24:258–64. doi:10.1007/s11095-006-9173-4.
106. Simmons CA, Alsberg E, Hsiong S, et al. Dual growth factor delivery and controlled scaffold degradation enhance in vivo bone formation by transplanted bone marrow stromal cells. Bone. 2004;35:562–9. doi:10.1016/j.bone.2004.02.027.
107. Huang Y-C, Kaigler D, Rice KG, et al. Combined angiogenic and osteogenic factor delivery enhances bone marrow stromal cell-driven bone regeneration. J Bone Miner Res. 2005;20:848–57. doi:10.1359/JBMR.041226.
108. He X, Yang X, Jabbari E. Combined effect of osteopontin and BMP-2 derived peptides grafted to an adhesive hydrogel on osteogenic and vasculogenic differentiation of marrow stromal cells. Langmuir. 2012;28:5387–97. doi:10.1021/la205005h.
109. Yilgor P, Hasirci N, Hasirci V. Sequential BMP-2/BMP-7 delivery from polyester nanocapsules. J Biomed Mater Res A. 2009;93:528–36. doi:10.1002/jbm.a.32520.
110. Wilson CG, Martín-Saavedra FM, Vilaboa N, Franceschi RT. Advanced BMP gene therapies for temporal and spatial control of bone regeneration. J Dent Res. 2013;92:409–17. doi:10.1177/0022034513483771.
111. Epstein NE. Complications due to the use of BMP/INFUSE in spine surgery: the evidence continues to mount. Surg Neurol Int. 2013;4:S343–52. doi:10.4103/2152-7806.114813.
112. Mroz TE, Wang JC, Hashimoto R, Norvell DC. Complications related to osteobiologics use in spine surgery: a systematic review. Spine (Phila Pa 1976). 2010;35:S86–S104. doi:10.1097/BRS.0b013e3181d81ef2.