title: Biomimetic hybrid scaffolds for engineering human tooth-ligament interfaces.
abstract: A major clinical challenge in the reconstruction of large oral and craniofacial defects is the neogenesis of osseous and ligamentous interfacial structures. Currently, oral regenerative medicine strategies are unpredictable for repair of tooth-supporting tissues destroyed as a consequence of trauma, chronic infection or surgical resection. Here, we demonstrate multi-scale computational design and fabrication of composite hybrid polymeric scaffolds for targeted cell transplantation of genetically modified human cells for the formation of human tooth dentin-ligament-bone complexes in vivo. The newly-formed tissues demonstrate the interfacial generation of parallel- and obliquely-oriented fibers that grow and traverse within the polycaprolactone (PCL)-poly(glycolic acid) (PGA) designed constructs forming tooth cementum-like tissue, ligament, and bone structures. This approach offers potential for the clinical implementation of customized periodontal scaffolds that may enable regeneration of multi-tissue interfaces required for oral, dental and craniofacial engineering applications.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-1078, USA.
authors.forename: Chan Ho
authors.initials: CH
authors.lastname: Park
authors.forename: Hector F
authors.initials: HF
authors.lastname: Rios
authors.forename: Qiming
authors.initials: Q
authors.lastname: Jin
authors.forename: Megan E
authors.initials: ME
authors.lastname: Bland
authors.forename: Colleen L
authors.initials: CL
authors.lastname: Flanagan
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hollister
authors.forename: William V
authors.initials: WV
authors.lastname: Giannobile
mesh_terms: D006801:Humans; D008022:Ligaments / Q000502:physiology*; D018716:Molecular Mimicry; D023822:Tissue Engineering; D014057:Tomography, X-Ray Computed; D014070:Tooth / Q000502:physiology*
references.citation: J Biomech. 2009 Aug 25;42(12):1961-6
references.pmid: 19501361
references.citation: J Clin Periodontol. 1998 Feb;25(2):134-44
references.pmid: 9495612
references.citation: Cell. 2007 Aug 24;130(4):601-10
references.pmid: 17719539
references.citation: Nat Biotechnol. 2003 Sep;21(9):1025-32
references.pmid: 12949568
references.citation: J Dent Res. 2000 Dec;79(12):1962-8
references.pmid: 11201046
references.citation: J Cell Biol. 2009 Feb 23;184(4):481-90
references.pmid: 19221195
references.citation: Adv Mater. 2009 Sep 4;21(32-33):3330-42
references.pmid: 20882500
references.citation: Science. 2009 Jun 26;324(5935):1673-7
references.pmid: 19556500
references.citation: Nat Rev Mol Cell Biol. 2009 Aug;10(8):538-49
references.pmid: 19603038
references.citation: Science. 2005 Nov 18;310(5751):1139-43
references.pmid: 16293750
references.citation: Med Res Rev. 2009 May;29(3):472-513
references.pmid: 19260070
references.citation: J Dent Res. 2004 Oct;83(10):751-6
references.pmid: 15381713
references.citation: Lancet. 1999 Jul;354 Suppl 1:SI32-4
references.pmid: 10437854
references.citation: Biomaterials. 2003 Jan;24(1):181-94
references.pmid: 12417192
references.citation: Curr Stem Cell Res Ther. 2010 Jun;5(2):168-74
references.pmid: 19941449
references.citation: Nat Mater. 2009 Jun;8(6):457-70
references.pmid: 19458646
references.citation: Periodontol 2000. 2006;40:11-28
references.pmid: 16398683
references.citation: Lancet. 2005 Nov 19;366(9499):1809-20
references.pmid: 16298220
references.citation: J Periodontal Res. 2006 Aug;41(4):311-5
references.pmid: 16827725
references.citation: Dent Clin North Am. 2006 Apr;50(2):245-63, ix
references.pmid: 16530061
references.citation: Nat Mater. 2009 Jan;8(1):15-23
references.pmid: 19096389
references.citation: Bone. 2009 Dec;45(6):1104-16
references.pmid: 19651256
references.citation: J Bone Miner Res. 2009 Sep;24(9):1507-11
references.pmid: 19653806
references.citation: Science. 1993 May 14;260(5110):920-6
references.pmid: 8493529
references.citation: J Dent Res. 2009 Sep;88(9):792-806
references.pmid: 19767575
references.citation: J Biomed Mater Res A. 2008 Jul;86(1):1-12
references.pmid: 18442111
references.citation: Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13661-5
references.pmid: 9391082
references.citation: Proc Natl Acad Sci U S A. 2008 Jun 10;105(23):7947-52
references.pmid: 18541916
references.citation: Nat Mater. 2005 Jul;4(7):518-24
references.pmid: 16003400