title: Enhanced chondrogenic differentiation of dental pulp stem cells using nanopatterned PEG-GelMA-HA hydrogels.
abstract: We have examined the effects of surface nanotopography and hyaluronic acid (HA) on in vitro chondrogenesis of dental pulp stem cells (DPSCs). Ultraviolet-assisted capillary force lithography was employed to fabricate well-defined nanostructured scaffolds of composite PEG-GelMA-HA hydrogels that consist of poly(ethylene glycol) dimethacrylate (PEGDMA), methacrylated gelatin (GelMA), and HA. Using this microengineered platform, we first demonstrated that DPSCs formed three-dimensional spheroids, which provide an appropriate environment for in vitro chondrogenic differentiation. We also found that DPSCs cultured on nanopatterned PEG-GelMA-HA scaffolds showed a significant upregulation of the chondrogenic gene markers (Sox9, Alkaline phosphatase, Aggrecan, Procollagen type II, and Procollagen type X), while downregulating the pluripotent stem cell gene, Nanog, and epithelial-mesenchymal genes (Twist, Snail, Slug) compared with tissue culture polystyrene-cultured DPSCs. Immunocytochemistry showed more extensive deposition of collagen type II in DPSCs cultured on the nanopatterned PEG-GelMA-HA scaffolds. These findings suggest that nanotopography and HA provide important cues for promoting chondrogenic differentiation of DPSCs.
authors.affiliation: 1 Department of Bioengineering, University of Washington , Seattle, Washington.
authors.forename: Cameron L
authors.initials: CL
authors.lastname: Nemeth
authors.forename: Kajohnkiart
authors.initials: K
authors.lastname: Janebodin
authors.forename: Alex E
authors.initials: AE
authors.lastname: Yuan
authors.forename: James E
authors.initials: JE
authors.lastname: Dennis
authors.forename: Morayma
authors.initials: M
authors.lastname: Reyes
authors.forename: Deok-Ho
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001672:Biocompatible Materials / Q000138:chemical synthesis; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D048429:Cell Size; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000502:physiology*; D003782:Dental Pulp / Q000166:cytology* / Q000502:physiology; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry; D008422:Materials Testing; D008689:Methacrylates / Q000737:chemistry*; D051379:Mice; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D013499:Surface Properties; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D008689:Methacrylates; C421283:poly(ethylene glycol)-dimethacrylate; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid
references.citation: J Bone Miner Res. 1997 Oct;12(10):1657-63
references.pmid: 9333126
references.citation: Biomaterials. 2010 Oct;31(28):7298-307
references.pmid: 20615545
references.citation: J Bone Joint Surg Am. 1998 Dec;80(12):1745-57
references.pmid: 9875932
references.citation: J Cell Biochem. 1996 Jun 15;61(4):569-77
references.pmid: 8806080
references.citation: Biomaterials. 2010 May;31(15):4360-6
references.pmid: 20202681
references.citation: Exp Cell Res. 2006 Jan 1;312(1):63-72
references.pmid: 16256983
references.citation: Biophys J. 2008 Jan 1;94(1):273-85
references.pmid: 17827231
references.citation: Acta Anat (Basel). 1995;154(1):63-78
references.pmid: 8714290
references.citation: Biomaterials. 2010 Mar;31(8):2163-75
references.pmid: 19995669
references.citation: Nano Lett. 2007 Jul;7(7):2122-8
references.pmid: 17567179
references.citation: Pharm Res. 2009 Mar;26(3):631-43
references.pmid: 19089601
references.citation: J Oral Pathol Med. 2008 Oct;37(9):571-4
references.pmid: 18331285
references.citation: Biochem Biophys Res Commun. 2002 Apr 12;292(4):819-25
references.pmid: 11944887
references.citation: Integr Biol (Camb). 2012 Sep;4(9):1019-33
references.pmid: 22890784
references.citation: Science. 2005 Nov 18;310(5751):1135-8
references.pmid: 16293749
references.citation: Biomacromolecules. 2000 Spring;1(1):31-8
references.pmid: 11709840
references.citation: Tissue Eng Part A. 2012 Oct;18(19-20):2073-83
references.pmid: 22655795
references.citation: Biomaterials. 2013 Mar;34(8):1942-53
references.pmid: 23245926
references.citation: Sci Technol Adv Mater. 2012 Dec 28;13(6):064217
references.pmid: 27877544
references.citation: Small. 2005 Aug;1(8-9):833-7
references.pmid: 17193534
references.citation: Acta Biomater. 2014 Apr;10(4):1632-45
references.pmid: 23851172
references.citation: J Appl Physiol (1985). 2013 Jun;114(11):1610-8
references.pmid: 23449937
references.citation: Biomaterials. 2010 Jul;31(21):5536-44
references.pmid: 20417964
references.citation: Proc Natl Acad Sci U S A. 2003 May 13;100(10):5807-12
references.pmid: 12716973
references.citation: Immunol Cell Biol. 1996 Apr;74(2):A1-7
references.pmid: 8724014
references.citation: Biomaterials. 2012 Jan;33(3):762-70
references.pmid: 22056285
references.citation: Biotechnol Appl Biochem. 2012 Mar-Apr;59(2):65-76
references.pmid: 23586787
references.citation: Biomaterials. 2005 Jun;26(16):3227-34
references.pmid: 15603817
references.citation: Tissue Eng Part A. 2012 Jan;18(1-2):67-79
references.pmid: 21770867
references.citation: PLoS One. 2011;6(11):e27526
references.pmid: 22087335
references.citation: Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13625-30
references.pmid: 11087820
references.citation: J Biol Chem. 2003 Oct 24;278(43):41862-70
references.pmid: 12917416
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):565-70
references.pmid: 20018748
references.citation: Biomaterials. 2013 Jul;34(22):5571-80
references.pmid: 23623322
references.citation: Biomacromolecules. 2010 Jul 12;11(7):1856-62
references.pmid: 20568737
references.citation: Cell. 2007 Nov 30;131(5):861-72
references.pmid: 18035408
references.citation: J Tissue Eng Regen Med. 2015 Jun;9(6):740-4
references.pmid: 23873763
references.citation: Biomaterials. 2012 Apr;33(11):3216-34
references.pmid: 22285466
references.citation: J Mech Behav Biomed Mater. 2012 Jul;11:41-52
references.pmid: 22658153
references.citation: Biomaterials. 2011 Oct;32(29):6929-45
references.pmid: 21762982
references.citation: Tissue Eng Part A. 2009 Apr;15(4):913-21
references.pmid: 18767972
references.citation: Tissue Eng. 2007 Aug;13(8):1867-77
references.pmid: 17518744
references.citation: Adv Mater. 2010 Nov 2;22(41):4551-66
references.pmid: 20803528
references.citation: Biomaterials. 2013 Oct;34(30):7257-68
references.pmid: 23834896
references.citation: Biomaterials. 2010 Sep;31(27):6968-80
references.pmid: 20619789
references.citation: Biomaterials. 2003 Sep;24(21):3825-34
references.pmid: 12818555
references.citation: Differentiation. 1995 Jul;59(1):25-34
references.pmid: 7589892
references.citation: Eur J Cell Biol. 2008 Sep;87(8-9):743-50
references.pmid: 18572273
references.citation: J Cell Biol. 2012 Apr 30;197(3):351-60
references.pmid: 22547406
references.citation: Tissue Cell. 2003 Feb;35(1):69-77
references.pmid: 12589731
references.citation: Cytometry A. 2013 Jan;83(1):38-47
references.pmid: 22837061
references.citation: J Biol Chem. 2006 Jan 20;281(3):1381-8
references.pmid: 16293629
references.citation: Regen Med. 2011 Nov;6(6):689-99
references.pmid: 22050521
references.citation: Langmuir. 2006 Jun 6;22(12):5419-26
references.pmid: 16732672
references.citation: Trends Biotechnol. 2011 Aug;29(8):399-408
references.pmid: 21549437
references.citation: Biol Cell. 2003 Mar-Apr;95(2):75-86
references.pmid: 12799063