title: Self-assembling peptide hydrogels modulate in vitro chondrogenesis of bovine bone marrow stromal cells.
abstract: Our objective was to test the hypothesis that self-assembling peptide hydrogel scaffolds provide cues that enhance the chondrogenic differentiation of bone marrow stromal cells (BMSCs). BMSCs were encapsulated within two unique peptide hydrogel sequences, and chondrogenesis was compared with that in agarose hydrogels. BMSCs in all three hydrogels underwent transforming growth factor-beta1-mediated chondrogenesis as demonstrated by comparable gene expression and biosynthesis of extracellular matrix molecules. Expression of an osteogenic marker was unchanged, and an adipogenic marker was suppressed by transforming growth factor-beta1 in all hydrogels. Cell proliferation occurred only in the peptide hydrogels, not in agarose, resulting in higher glycosaminoglycan content and more spatially uniform proteoglycan and collagen type II deposition. The G1-positive aggrecan produced in peptide hydrogels was predominantly the full-length species, whereas that in agarose was predominantly the aggrecanase product G1-NITEGE. Unique cell morphologies were observed for BMSCs in each peptide hydrogel sequence, with extensive cell-cell contact present for both, whereas BMSCs in agarose remained rounded over 21 days in culture. Differences in cell morphology within the two peptide scaffolds may be related to sequence-specific cell adhesion. Taken together, this study demonstrates that self-assembling peptide hydrogels enhance chondrogenesis compared with agarose as shown by extracellular matrix production, DNA content, and aggrecan molecular structure.
authors.affiliation: Department of Biological Engineering, MIT, Cambridge, Massachusetts 02139, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Kopesky
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Vanderploeg
authors.forename: John S
authors.initials: JS
authors.lastname: Sandy
authors.forename: Bodo
authors.initials: B
authors.lastname: Kurz
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Grodzinsky
mesh_terms: D000199:Actins / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D048430:Cell Shape / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects* / Q000235:genetics; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000378:metabolism; D020100:Hydrogels / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010455:Peptides / Q000494:pharmacology*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D000199:Actins; D053674:Aggrecans; D024042:Collagen Type I; D024043:Collagen Type II; D006025:Glycosaminoglycans; D020100:Hydrogels; D010455:Peptides; D004247:DNA
references.citation: Stem Cells. 2004;22(3):313-23
references.pmid: 15153608
references.citation: Pharm Res. 2008 Mar;25(3):692-9
references.pmid: 17404809
references.citation: Arthritis Res Ther. 2007;9(3):213
references.pmid: 17561986
references.citation: Cell Tissue Res. 2005 Feb;319(2):243-53
references.pmid: 15654654
references.citation: Biomaterials. 2007 Feb;28(6):1071-83
references.pmid: 17123602
references.citation: Jpn J Vet Res. 2006 Feb;53(3-4):127-39
references.pmid: 16544933
references.citation: Anal Biochem. 1988 Oct;174(1):168-76
references.pmid: 2464289
references.citation: J Mater Sci Mater Med. 2009 Dec;20 Suppl 1:S49-60
references.pmid: 18560767
references.citation: PLoS One. 2006 Dec 27;1:e119
references.pmid: 17205123
references.citation: Arthritis Rheum. 2006 Oct;54(10):3075-8
references.pmid: 17009225
references.citation: J Orthop Res. 1992 Nov;10(6):745-58
references.pmid: 1403287
references.citation: Tissue Eng Part A. 2009 May;15(5):1041-52
references.pmid: 19119920
references.citation: Osteoarthritis Cartilage. 2002 Jan;10(1):13-22
references.pmid: 11795979
references.citation: Exp Cell Res. 1998 Jan 10;238(1):265-72
references.pmid: 9457080
references.citation: J Struct Biol. 2003 Sep;143(3):242-57
references.pmid: 14572479
references.citation: Matrix Biol. 2008 Jan;27(1):12-21
references.pmid: 17689060
references.citation: Biomaterials. 2005 Jun;26(16):3341-51
references.pmid: 15603830
references.citation: Cell. 1982 Aug;30(1):215-24
references.pmid: 7127471
references.citation: Tissue Eng. 2003 Feb;9(1):27-36
references.pmid: 12625951
references.citation: Nano Lett. 2006 Sep;6(9):2086-90
references.pmid: 16968030
references.citation: Biomed Mater Eng. 2008;18(1 Suppl):S55-70
references.pmid: 18334724
references.citation: Connect Tissue Res. 1982;9(4):247-8
references.pmid: 6215207
references.citation: Trends Biotechnol. 2002 Jan;20(1):16-21
references.pmid: 11742673
references.citation: J Biomed Mater Res A. 2008 Nov;87(2):494-504
references.pmid: 18186067
references.citation: J Cell Biochem. 2006 Jan 1;97(1):33-44
references.pmid: 16215986
references.citation: Nat Clin Pract Rheumatol. 2008 Jul;4(7):371-80
references.pmid: 18477997
references.citation: J Orthop Res. 2008 Mar;26(3):322-31
references.pmid: 17960654
references.citation: Differentiation. 2003 Jun;71(4-5):262-70
references.pmid: 12823227
references.citation: Proc Natl Acad Sci U S A. 2007 May 8;104(19):7791-6
references.pmid: 17470802
references.citation: J Biomech Eng. 2000 Jun;122(3):252-60
references.pmid: 10923293
references.citation: J Anat. 2006 Oct;209(4):469-80
references.pmid: 17005019
references.citation: Bioessays. 2000 Feb;22(2):138-47
references.pmid: 10655033
references.citation: Arthritis Rheum. 2004 Sep;50(9):2839-48
references.pmid: 15457452
references.citation: Arthritis Rheum. 2007 Jun;56(6):1869-79
references.pmid: 17530715
references.citation: J Cell Physiol. 2008 Oct;217(1):145-54
references.pmid: 18452154
references.citation: Proc Natl Acad Sci U S A. 2006 May 23;103(21):8155-60
references.pmid: 16698918
references.citation: Stem Cells. 2007 Mar;25(3):655-63
references.pmid: 17124008
references.citation: Science. 1999 Apr 2;284(5411):143-7
references.pmid: 10102814
references.citation: Biotechnol Appl Biochem. 2007 Feb;46(Pt 2):73-84
references.pmid: 17227284
references.citation: Int J Biochem Cell Biol. 2008;40(12):2720-38
references.pmid: 18620888
references.citation: Arch Biochem Biophys. 2000 Feb 1;374(1):79-85
references.pmid: 10640399
references.citation: J Biomater Sci Polym Ed. 2002;13(3):225-36
references.pmid: 12102591
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20641-6
references.pmid: 19095799
references.citation: Nucleic Acids Res. 2001 May 1;29(9):e45
references.pmid: 11328886
references.citation: Biomaterials. 2008 Aug;29(22):3201-12
references.pmid: 18462789
references.citation: Biotechnol Bioeng. 2006 Apr 20;93(6):1152-63
references.pmid: 16470881
references.citation: J Biol Chem. 2006 Jan 27;281(4):2390-400
references.pmid: 16257955
references.citation: Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9996-10001
references.pmid: 12119393
references.citation: Cell Biochem Biophys. 2007;49(2):73-83
references.pmid: 17906362
references.citation: Nat Rev Mol Cell Biol. 2005 Sep;6(9):726-37
references.pmid: 16103873
references.citation: Tissue Eng Part A. 2009 Feb;15(2):243-54
references.pmid: 19193129
references.citation: Tissue Eng Part A. 2008 Feb;14(2):227-36
references.pmid: 18333775
references.citation: PLoS One. 2007 Feb 07;2(2):e190
references.pmid: 17285144
references.citation: Osteoarthritis Cartilage. 2006 Feb;14(2):179-89
references.pmid: 16257243
references.citation: Int J Dev Biol. 1995 Dec;39(6):881-93
references.pmid: 8901191
references.citation: Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3334-8
references.pmid: 7682699
references.citation: Osteoarthritis Cartilage. 2008 Sep;16(9):1092-100
references.pmid: 18294870
references.citation: J Biol Chem. 2004 May 7;279(19):19502-11
references.pmid: 14960571
references.citation: Exp Cell Res. 2001 Aug 15;268(2):189-200
references.pmid: 11478845