title: Covalently immobilized platelet-derived growth factor-BB promotes angiogenesis in biomimetic poly(ethylene glycol) hydrogels.
abstract: The field of tissue engineering is severely limited by a lack of microvascularization in tissue engineered constructs. Biomimetic poly(ethylene glycol) hydrogels containing covalently immobilized platelet-derived growth factor BB (PDGF-BB) were developed to promote angiogenesis. Poly(ethylene glycol) hydrogels resist protein absorption and subsequent non-specific cell adhesion, thus providing a "blank slate", which can be modified through the incorporation of cell adhesive ligands and growth factors. PDGF-BB is a key angiogenic protein able to support neovessel stabilization by inducing functional anastomoses and recruiting pericytes. Due to the widespread effects of PDGF in the body and a half-life of only 30 min in circulating blood, immobilization of PDGF-BB may be necessary. In this work bioactive, covalently immobilized PDGF-BB was shown to induce tubulogenesis on two-dimensional modified surfaces, migration in three-dimensional (3D) degradable hydrogels and angiogenesis in a mouse cornea micropocket angiogenesis assay. Covalently immobilized PDGF-BB was also used in combination with covalently immobilized fibroblast growth factor-2, which led to significantly increased endothelial cell migration in 3D degradable hydrogels compared with the presentation of each factor alone. When a co-culture of endothelial cells and mouse pericyte precursor 10T1/2 cells was seeded onto modified surfaces tubule formation was independent of surface modifications with covalently immobilized growth factors. Furthermore, the combination of soluble PDGF-BB and immobilized PDGF-BB induced a more robust vascular response compared with soluble PDGF-BB alone when implanted into an in vivo mouse cornea micropocket angiogenesis assay. Based on these results, we believe bioactive hydrogels can be tailored to improve the formation of functional microvasculature for tissue engineering.
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX 77005, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Saik
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Gould
authors.forename: Emily M
authors.initials: EM
authors.lastname: Watkins
authors.forename: Mary E
authors.initials: ME
authors.lastname: Dickinson
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: West
mesh_terms: D000818:Animals; D000077214:Becaplermin; D001672:Biocompatible Materials / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002254:Carbonates / Q000737:chemistry / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D055767:Immobilized Proteins / Q000494:pharmacology*; D020007:Implants, Experimental; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D015203:Reproducibility of Results; D013388:Succinimides / Q000737:chemistry / Q000494:pharmacology; D013499:Surface Properties / Q000187:drug effects
chemical_list: D001672:Biocompatible Materials; D015415:Biomarkers; D002254:Carbonates; D020100:Hydrogels; D055767:Immobilized Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D013388:Succinimides; D016222:Fibroblast Growth Factor 2; C085786:succinimidyl carbonate; D000077214:Becaplermin; D011092:Polyethylene Glycols; D020782:Matrix Metalloproteinases
references.citation: J Biomater Sci Polym Ed. 2004;15(6):701-26
references.pmid: 15255521
references.citation: Nature. 2006 Jul 27;442(7101):453-6
references.pmid: 16799567
references.citation: J Bone Joint Surg Am. 2008 Feb;90 Suppl 1:48-54
references.pmid: 18292357
references.citation: Biomacromolecules. 2009 Dec 14;10(12):3193-8
references.pmid: 19891448
references.citation: J Control Release. 2010 Apr 2;143(1):45-52
references.pmid: 19963026
references.citation: Nature. 2004 Mar 11;428(6979):138-9
references.pmid: 15014486
references.citation: FASEB J. 2001 May;15(7):1239-41
references.pmid: 11344100
references.citation: Arterioscler Thromb Vasc Biol. 2004 Aug;24(8):1384-90
references.pmid: 15217807
references.citation: Biomaterials. 2005 Jun;26(16):3227-34
references.pmid: 15603817
references.citation: Endocrinology. 1989 Apr;124(4):1841-8
references.pmid: 2924726
references.citation: FASEB J. 2009 Jan;23(1):153-63
references.pmid: 18827023
references.citation: J Cell Biol. 1998 May 4;141(3):805-14
references.pmid: 9566978
references.citation: Dev Dyn. 2009 Sep;238(9):2318-26
references.pmid: 19253403
references.citation: J Biomater Sci Polym Ed. 2009;20(12):1763-79
references.pmid: 19723440
references.citation: J Cell Sci. 2005 Aug 15;118(Pt 16):3759-68
references.pmid: 16105884
references.citation: Invest Ophthalmol Vis Sci. 1996 Jul;37(8):1625-32
references.pmid: 8675406
references.citation: EXS. 2005;(94):115-25
references.pmid: 15617474
references.citation: Cold Spring Harb Protoc. 2010 Apr;2010(4):pdb.prot5416
references.pmid: 20360370
references.citation: Biomacromolecules. 2007 Jan;8(1):42-9
references.pmid: 17206786
references.citation: J Mol Med (Berl). 2008 Jul;86(7):785-9
references.pmid: 18392794
references.citation: Ann Biomed Eng. 2007 Feb;35(2):190-200
references.pmid: 17180465
references.citation: Mol Cell Biochem. 2010 Feb;335(1-2):1-11
references.pmid: 19711176
references.citation: Adv Drug Deliv Rev. 2002 Jun 17;54(4):459-76
references.pmid: 12052709
references.citation: Physiol Rev. 1999 Oct;79(4):1283-316
references.pmid: 10508235
references.citation: Nat Med. 1996 Sep;2(9):1022-7
references.pmid: 8782461
references.citation: Nat Med. 2003 May;9(5):604-13
references.pmid: 12669032
references.citation: Tissue Eng. 2006 Jan;12(1):9-19
references.pmid: 16499438
references.citation: J Pathol. 2003 Jul;200(4):448-64
references.pmid: 12845612
references.citation: Ann Biomed Eng. 2010 Feb;38(2):225-34
references.pmid: 19937274
references.citation: BioDrugs. 2008;22(5):315-29
references.pmid: 18778113
references.citation: Histol Histopathol. 2009 Jul;24(7):909-69
references.pmid: 19475537
references.citation: Anat Rec (Hoboken). 2009 Mar;292(3):333-41
references.pmid: 19248165
references.citation: Biomaterials. 2008 Dec;29(35):4676-83
references.pmid: 18801569
references.citation: Endocr Rev. 1997 Feb;18(1):26-45
references.pmid: 9034785
references.citation: J Clin Invest. 1995 Aug;96(2):1169-75
references.pmid: 7635955
references.citation: Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1376-86
references.pmid: 16565371