title: Scaffold structure and fabrication method affect proinflammatory milieu in three-dimensional-cultured chondrocytes.
abstract: Cartilage tissue engineering has emerged as an attractive therapeutic option for repairing damaged cartilage tissue in the arthritic joint. High levels of proinflammatory cytokines present at arthritic joints can cause cartilage destruction and instability of the engineered cartilage tissue, and thus it is critical to engineer strong and stable cartilage that is resistant to the inflammatory environment. In this study, we demonstrate that scaffolding materials with different pore sizes and fabrication methods influence the microenvironment of chondrocytes and the response of these cells to proinflammatory cytokines, interleukin-1beta, and tumor necrosis factor alpha. Silk scaffolds prepared using the organic solvent hexafluoroisopropanol as compared to an aqueous-based method, as well as those with larger pore sizes, supported the deposition of higher cartilage matrix levels and lower expression of cartilage matrix degradation-related genes, as well as lower expression of endogenous proinflammatory cytokines IL-1β in articular chondrocytes. These biochemical properties could be related to the physical properties of the scaffolds such as the water uptake and the tendency to leach or adsorb proinflammatory cytokines. Thus, scaffold structure may influence the behavior of chondrocytes by influencing the microenvironment under inflammatory conditions, and should be considered as an important component for bioengineering stable cartilage tissues.
authors.affiliation: Program in Cell, Molecular, and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts, 02111.
authors.forename: Heenam
authors.initials: H
authors.lastname: Kwon
authors.forename: Roshni S
authors.initials: RS
authors.lastname: Rainbow
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.forename: Carrie K
authors.initials: CK
authors.lastname: Hui
authors.forename: Dana M
authors.initials: DM
authors.lastname: Cairns
authors.forename: Rucsanda C
authors.initials: RC
authors.lastname: Preda
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
authors.forename: Li
authors.initials: L
authors.lastname: Zeng
mesh_terms: D000818:Animals; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000096:biosynthesis*; D047011:Silk / Q000009:adverse effects* / Q000737:chemistry; D054457:Tissue Scaffolds / Q000009:adverse effects* / Q000737:chemistry
chemical_list: D053583:Interleukin-1beta; D047011:Silk
keywords: cartilage matrix production; cytokine release; pro-inflammatory cytokines; scaffold; water uptake
references.citation: J Bone Miner Res. 2014 Feb;29(2):304-15
references.pmid: 23857747
references.citation: Osteoarthritis Cartilage. 2002 Jun;10(6):432-63
references.pmid: 12056848
references.citation: Knee. 2003 Mar;10(1):93-6
references.pmid: 12649034
references.citation: Osteoarthritis Cartilage. 2004 Dec;12(12):963-73
references.pmid: 15564063
references.citation: Nat Genet. 1997 Jun;16(2):174-8
references.pmid: 9171829
references.citation: Biomaterials. 2010 Apr;31(10):2798-805
references.pmid: 20053441
references.citation: Biomaterials. 2005 May;26(15):2479-89
references.pmid: 15585250
references.citation: Science. 2012 Dec 7;338(6112):1353-6
references.pmid: 23138980
references.citation: J Biomater Appl. 1999 Oct;14(2):184-91
references.pmid: 10549004
references.citation: J Rheumatol. 1997 Feb;24(2):365-71
references.pmid: 9034998
references.citation: Ann Biomed Eng. 2002 Sep;30(8):1046-56
references.pmid: 12449765
references.citation: Biomaterials. 2010 May;31(15):4304-12
references.pmid: 20219243
references.citation: Biomaterials. 2011 Feb;32(6):1508-16
references.pmid: 21093907
references.citation: Drug Discov Today. 2009 Oct;14(19-20):913-25
references.pmid: 19651235
references.citation: Arthritis Rheum. 2006 Aug;54(8):2462-70
references.pmid: 16868966
references.citation: J Biomed Mater Res. 2001 Nov;57(2):190-9
references.pmid: 11484181
references.citation: Clin Orthop Relat Res. 2001 Oct;(391 Suppl):S108-15
references.pmid: 11603695
references.citation: Osteoarthritis Cartilage. 2012 Dec;20(12):1447-50
references.pmid: 22897882
references.citation: Nat Genet. 1999 May;22(1):85-9
references.pmid: 10319868
references.citation: J Control Release. 2009 Mar 4;134(2):111-7
references.pmid: 19100794
references.citation: Expert Opin Biol Ther. 2012 Oct;12(10):1361-82
references.pmid: 22784026
references.citation: Arthroscopy. 2001 Sep;17(7):724-31
references.pmid: 11536091
references.citation: J Biomed Mater Res. 1996 Feb;30(2):145-55
references.pmid: 9019478
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2130-5
references.pmid: 19179282
references.citation: Arthritis Rheum. 2011 Sep;63(9):2732-43
references.pmid: 21590680
references.citation: J Biomater Appl. 2011 Jan;25(5):429-44
references.pmid: 20042429
references.citation: Arthritis Res Ther. 2007;9(3):213
references.pmid: 17561986
references.citation: Acta Biomater. 2013 May;9(5):6563-75
references.pmid: 23333441
references.citation: Osteoarthritis Cartilage. 2013 Oct;21(10):1436-42
references.pmid: 23774472
references.citation: J Biomed Mater Res A. 2006 Aug;78(2):324-34
references.pmid: 16637042
references.citation: Arthroscopy. 2005 Nov;21(11):1342-7
references.pmid: 16325085
references.citation: Biomaterials. 2013 May;34(16):3970-3983
references.pmid: 23453201
references.citation: Biomaterials. 1996 Jan;17(2):137-46
references.pmid: 8624390
references.citation: Curr Rheumatol Rep. 2000 Dec;2(6):447-53
references.pmid: 11123096
references.citation: Adv Drug Deliv Rev. 2008 Jan 14;60(2):243-62
references.pmid: 17976858
references.citation: Biochem Biophys Res Commun. 2007 Jan 5;352(1):135-41
references.pmid: 17112464
references.citation: Biomacromolecules. 2009 Mar 9;10(3):541-6
references.pmid: 19173557
references.citation: Acta Biomater. 2009 Feb;5(2):670-9
references.pmid: 18951858
references.citation: Eur Cell Mater. 2006 Oct 26;12:49-56; discussion 56
references.pmid: 17068722
references.citation: Biomaterials. 2005 May;26(15):2775-85
references.pmid: 15585282
references.citation: J Tissue Eng Regen Med. 2011 Jul;5(7):578-88
references.pmid: 21695799
references.citation: Arthritis Rheum. 2001 Jun;44(6):1237-47
references.pmid: 11407681
references.citation: Acta Biomater. 2012 Jan;8(1):289-301
references.pmid: 22019518
references.citation: Biomaterials. 2005 Jul;26(21):4442-52
references.pmid: 15701373
references.citation: Int J Mol Med. 2008 Nov;22(5):691-9
references.pmid: 18949392
references.citation: Eur Cell Mater. 2013 May 02;25:248-67
references.pmid: 23636950
references.citation: J Control Release. 2007 Dec 4;124(1-2):51-9
references.pmid: 17904679
references.citation: Am J Sports Med. 2011 Dec;39(12):2595-603
references.pmid: 22021585
references.citation: Annu Rev Biomed Eng. 2004;6:131-56
references.pmid: 15255765
references.citation: Tissue Eng Part B Rev. 2008 Jun;14(2):179-86
references.pmid: 18544015
references.citation: Biomaterials. 2007 Mar;28(9):1664-71
references.pmid: 17196648
references.citation: Head Face Med. 2010 Jul 19;6:17
references.pmid: 20642842
references.citation: J Biomed Mater Res A. 2011 Jun 15;97(4):414-22
references.pmid: 21484985
references.citation: Lancet. 2011 Jun 18;377(9783):2115-26
references.pmid: 21684382
references.citation: J Immunol. 1990 Jan 15;144(2):499-505
references.pmid: 2104896
references.citation: Osteoarthritis Cartilage. 2013 Jul;21(7):918-22
references.pmid: 23598178
references.citation: Matrix Biol. 2000 Nov;19(6):549-53
references.pmid: 11068209
references.citation: J Biosci Bioeng. 2009 Jul;108(1):68-75
references.pmid: 19577196
references.citation: Biomaterials. 2007 Jul;28(20):3074-82
references.pmid: 17428532
references.citation: Biomacromolecules. 2004 May-Jun;5(3):718-26
references.pmid: 15132652
references.citation: Bull NYU Hosp Jt Dis. 2007;65(1):51-60
references.pmid: 17539762
references.citation: Biorheology. 2002;39(1-2):237-46
references.pmid: 12082286
references.citation: J Orthop Res. 2010 Apr;28(4):529-36
references.pmid: 19813241
references.citation: J Control Release. 2008 Apr 7;127(1):12-21
references.pmid: 18280603
references.citation: J Orthop Res. 2013 Oct;31(10):1501-6
references.pmid: 23818453
references.citation: Nat Med. 2010 Jun;16(6):687-93
references.pmid: 20495569
references.citation: J Endocrinol. 2009 Jun;201(3):309-20
references.pmid: 19443863
references.citation: Biotechnol Bioeng. 2004 Nov 5;88(3):379-91
references.pmid: 15486944
references.citation: Arthritis Rheum. 2007 Oct;56(10):3297-306
references.pmid: 17907154
references.citation: J Biomed Mater Res B Appl Biomater. 2008 Apr;85(1):252-60
references.pmid: 17973245
references.citation: J Biomed Mater Res A. 2004 Oct 1;71(1):25-34
references.pmid: 15316936
references.citation: Trends Biotechnol. 2009 May;27(5):307-14
references.pmid: 19329205
references.citation: Biomaterials. 2005 Feb;26(4):433-41
references.pmid: 15275817
references.citation: Arthritis Res Ther. 2005;7(4):R904-14
references.pmid: 15987493
references.citation: Inflamm Res. 2004 Aug;53(8):377-89
references.pmid: 15316669
references.citation: Biomaterials. 2012 Dec;33(35):8967-74
references.pmid: 22999467
references.citation: J Bone Joint Surg Br. 2005 Apr;87(4):445-9
references.pmid: 15795189