title: Osteochondral tissue regeneration using a bilayered composite hydrogel with modulating dual growth factor release kinetics in a rabbit model.
abstract: Biodegradable oligo(poly(ethylene glycol) fumarate) (OPF) composite hydrogels have been investigated for the delivery of growth factors (GFs) with the aid of gelatin microparticles (GMPs) and stem cell populations for osteochondral tissue regeneration. In this study, a bilayered OPF composite hydrogel that mimics the distinctive hierarchical structure of native osteochondral tissue was utilized to investigate the effect of transforming growth factor-β3 (TGF-β3) with varying release kinetics and/or insulin-like growth factor-1 (IGF-1) on osteochondral tissue regeneration in a rabbit full-thickness osteochondral defect model. The four groups investigated included (i) a blank control (no GFs), (ii) GMP-loaded IGF-1 alone, (iii) GMP-loaded IGF-1 and gel-loaded TGF-β3, and (iv) GMP-loaded IGF-1 and GMP-loaded TGF-β3 in OPF composite hydrogels. The results of an in vitro release study demonstrated that TGF-β3 release kinetics could be modulated by the GF incorporation method. At 12weeks post-implantation, the quality of tissue repair in both chondral and subchondral layers was analyzed based on quantitative histological scoring. All groups incorporating GFs resulted in a significant improvement in cartilage morphology compared to the control. Single delivery of IGF-1 showed higher scores in subchondral bone morphology as well as chondrocyte and glycosaminoglycan amount in adjacent cartilage tissue when compared to a dual delivery of IGF-1 and TGF-β3, independent of the TGF-β3 release kinetics. The results suggest that although the dual delivery of TGF-β3 and IGF-1 may not synergistically enhance the quality of engineered tissue, the delivery of IGF-1 alone from bilayered composite hydrogels positively affects osteochondral tissue repair and holds promise for osteochondral tissue engineering applications.
authors.affiliation: Department of Bioengineering, Rice University, Houston, USA.
authors.forename: Kyobum
authors.initials: K
authors.lastname: Kim
authors.forename: Johnny
authors.initials: J
authors.lastname: Lam
authors.forename: Steven
authors.initials: S
authors.lastname: Lu
authors.forename: Patrick P
authors.initials: PP
authors.lastname: Spicer
authors.forename: Aline
authors.initials: A
authors.lastname: Lueckgen
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Mark E
authors.initials: ME
authors.lastname: Wong
authors.forename: John A
authors.initials: JA
authors.lastname: Jansen
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Mikos
authors.forename: F Kurtis
authors.initials: FK
authors.lastname: Kasper
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002356:Cartilage / Q000187:drug effects / Q000502:physiology; D019902:Chondrocytes / Q000187:drug effects / Q000502:physiology; D005269:Femur / Q000293:injuries; D005780:Gelatin / Q000737:chemistry; D006025:Glycosaminoglycans / Q000378:metabolism; D020100:Hydrogels; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011817:Rabbits; D053782:Transforming Growth Factor beta3 / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D006025:Glycosaminoglycans; D020100:Hydrogels; D011091:Polyesters; D053782:Transforming Growth Factor beta3; C469550:oligo(poly(ethylene glycol)fumarate); D011092:Polyethylene Glycols; D007334:Insulin-Like Growth Factor I; D005780:Gelatin
references.citation: Nat Protoc. 2012 May 31;7(6):1219-27
references.pmid: 22653160
references.citation: Tissue Eng. 2002 Oct;8(5):853-61
references.pmid: 12459064
references.citation: J Orthop Res. 1999 Jul;17(4):475-87
references.pmid: 10459752
references.citation: J Bone Joint Surg Am. 2003;85-A Suppl 3:75-81
references.pmid: 12925613
references.citation: Osteoarthritis Cartilage. 2007 Feb;15(2):187-97
references.pmid: 16965923
references.citation: Lancet. 2010 Aug 7;376(9739):440-8
references.pmid: 20692530
references.citation: J Biomed Mater Res A. 2010 Feb;92(2):806-16
references.pmid: 19280636
references.citation: J Orthop Res. 2001 Jul;19(4):738-49
references.pmid: 11518286
references.citation: J Biomater Sci Polym Ed. 1999;10(1):79-94
references.pmid: 10091924
references.citation: Tissue Eng Part A. 2009 Aug;15(8):2163-75
references.pmid: 19413492
references.citation: Acta Biomater. 2010 Aug;6(8):2920-31
references.pmid: 20197126
references.citation: J Am Acad Orthop Surg. 1994 Jul;2(4):192-201
references.pmid: 10709009
references.citation: J Orthop Res. 2009 Aug;27(8):1109-15
references.pmid: 19195026
references.citation: J Biomed Mater Res A. 2010 Dec 15;95(4):982-92
references.pmid: 20872747
references.citation: Biomaterials. 2005 Dec;26(34):7095-103
references.pmid: 16023196
references.citation: Clin Anat. 2014 Apr;27(3):451-4
references.pmid: 22730047
references.citation: Biomaterials. 2011 Sep;32(27):6425-34
references.pmid: 21652067
references.citation: Biomaterials. 2000 Mar;21(5):431-40
references.pmid: 10674807
references.citation: J Biomed Mater Res A. 2009 Mar 15;88(4):889-97
references.pmid: 18381637
references.citation: J Biomed Mater Res A. 2012 Sep;100(9):2526-36
references.pmid: 22492677
references.citation: Tissue Eng Part B Rev. 2011 Aug;17(4):281-99
references.pmid: 21510824
references.citation: Adv Biochem Eng Biotechnol. 2010;123:163-200
references.pmid: 20535603
references.citation: Ann N Y Acad Sci. 2010 Mar;1192:230-7
references.pmid: 20392241
references.citation: J Am Acad Orthop Surg. 2003 Nov-Dec;11(6):421-30
references.pmid: 14686827
references.citation: Biomacromolecules. 2009 Mar 9;10(3):541-6
references.pmid: 19173557
references.citation: Adv Orthop. 2012;2012:528423
references.pmid: 22655202
references.citation: Tissue Eng Part A. 2011 Sep;17(17-18):2259-65
references.pmid: 21542714
references.citation: J Control Release. 2005 Aug 18;106(1-2):162-71
references.pmid: 15972241
references.citation: J Biomed Mater Res A. 2004 Jun 1;69(3):535-43
references.pmid: 15127400
references.citation: Wound Repair Regen. 2007 May-Jun;15(3):413-21
references.pmid: 17537129
references.citation: Clin Orthop Relat Res. 2011 Oct;469(10):2706-15
references.pmid: 21403984
references.citation: Osteoarthritis Cartilage. 2010 Dec;18(12):1608-19
references.pmid: 20851201
references.citation: Ann Biomed Eng. 2011 Oct;39(10):2491-500
references.pmid: 21833681
references.citation: J Bone Joint Surg Br. 2002 Mar;84(2):276-88
references.pmid: 11922373
references.citation: Biomaterials. 2009 May;30(14):2741-52
references.pmid: 19232711
references.citation: Osteoarthritis Cartilage. 2006 May;14(5):403-12
references.pmid: 16413799
references.citation: J Biomed Mater Res. 2002 Aug;61(2):169-79
references.pmid: 12061329
references.citation: J Control Release. 2005 Jan 3;101(1-3):111-25
references.pmid: 15588898
references.citation: J Control Release. 2003 Sep 4;91(3):299-313
references.pmid: 12932709
references.citation: Osteoarthritis Cartilage. 2003 Jan;11(1):55-64
references.pmid: 12505488
references.citation: Osteoarthritis Cartilage. 2007 Oct;15(10):1178-89
references.pmid: 17502159
references.citation: J Mech Behav Biomed Mater. 2012 Jul;11:92-101
references.pmid: 22658158
references.citation: Biomaterials. 2007 Jul;28(21):3217-27
references.pmid: 17445882
references.citation: Acta Biomater. 2008 Sep;4(5):1126-38
references.pmid: 18474452
references.citation: Biomaterials. 2008 Apr;29(10):1518-25
references.pmid: 18166223
references.citation: Tissue Eng Part B Rev. 2013 Aug;19(4):327-52
references.pmid: 23249320
references.citation: Pharm Res. 2008 Oct;25(10):2370-8
references.pmid: 18663411
references.citation: J Biomed Mater Res A. 2005 Oct 1;75(1):156-67
references.pmid: 16052490
references.citation: J Rheumatol. 1998 Aug;25(8):1578-84
references.pmid: 9712104
references.citation: Acta Biomater. 2010 Jan;6(1):39-47
references.pmid: 19660580
references.citation: Trends Biotechnol. 2009 May;27(5):307-14
references.pmid: 19329205
references.citation: Crit Rev Oral Biol Med. 1992;3(3):269-305
references.pmid: 1571474
references.citation: Exp Cell Res. 1997 Dec 15;237(2):318-25
references.pmid: 9434627
references.citation: Exp Cell Res. 2001 Aug 15;268(2):189-200
references.pmid: 11478845