title: Microsphere-based seamless scaffolds containing macroscopic gradients of encapsulated factors for tissue engineering.
abstract: Spatial and temporal control of bioactive signals in three-dimensional (3D) tissue engineering scaffolds is greatly desired. Coupled together, these attributes may mimic and maintain complex signal patterns, such as those observed during axonal regeneration or neovascularization. Seamless polymer constructs may provide a route to achieve spatial control of signal distribution. In this study, a novel microparticle-based scaffold fabrication technique is introduced as a method to create 3D scaffolds with spatial control over model dyes using uniform poly(D,L-lactide-co-glycolide) microspheres. Uniform microspheres were produced using the Precision Particle Fabrication technique. Scaffolds were assembled by flowing microsphere suspensions into a cylindrical glass mold, and then microspheres were physically attached to form a continuous scaffold using ethanol treatment. An ethanol soak of 1 h was found to be optimum for improved mechanical characteristics. Morphological and physical characterization of the scaffolds revealed that microsphere matrices were porous (41.1 +/- 2.1%) and well connected, and their compressive stiffness ranged from 142 to 306 kPa. Culturing chondrocytes on the scaffolds revealed the compatibility of these substrates with cell attachment and viability. In addition, bilayered, multilayered, and gradient scaffolds were fabricated, exhibiting excellent spatial control and resolution. Such novel scaffolds can serve as sustained delivery devices of heterogeneous signals in a continuous and seamless manner, and may be particularly useful in future interfacial tissue engineering investigations.
authors.affiliation: Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence, Kansas 66047, USA.
authors.forename: Milind
authors.initials: M
authors.lastname: Singh
authors.forename: Casey P
authors.initials: CP
authors.lastname: Morris
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: Michael S
authors.initials: MS
authors.lastname: Detamore
authors.forename: Cory
authors.initials: C
authors.lastname: Berkland
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002470:Cell Survival; D019902:Chondrocytes / Q000166:cytology*; D004867:Equipment Design; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D016062:Porosity; D011312:Pressure; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D036341:Intercellular Signaling Peptides and Proteins
references.citation: J Bone Joint Surg Br. 2004 Nov;86(8):1200-8
references.pmid: 15568538
references.citation: J Biomater Sci Polym Ed. 1995;7(1):23-38
references.pmid: 7662615
references.citation: Neuroscience. 2003;122(2):381-9
references.pmid: 14614904
references.citation: Biomacromolecules. 2008 Jul;9(7):1818-25
references.pmid: 18517248
references.citation: J Biomed Mater Res B Appl Biomater. 2008 Aug;86(2):396-406
references.pmid: 18161819
references.citation: Tissue Eng. 2006 Apr;12(4):789-800
references.pmid: 16674292
references.citation: Matrix Biol. 2005 May;24(3):208-18
references.pmid: 15896949
references.citation: Biotechnol Prog. 2003 Mar-Apr;19(2):243-53
references.pmid: 12675556
references.citation: Biomaterials. 2008 Apr;29(10):1518-25
references.pmid: 18166223
references.citation: Biomaterials. 1999 Jun;20(11):1057-62
references.pmid: 10378806
references.citation: J Biomed Mater Res A. 2004 Feb 1;68(2):235-43
references.pmid: 14704965
references.citation: Bioessays. 2000 Jul;22(7):599-602
references.pmid: 10878572
references.citation: Langmuir. 2008 Mar 18;24(6):2294-317
references.pmid: 18220435
references.citation: J Biomed Mater Res A. 2006 Aug;78(2):213-21
references.pmid: 16892507
references.citation: Biomaterials. 2008 Jan;29(2):185-92
references.pmid: 17950842
references.citation: J Biomed Mater Res. 2001 May;55(2):242-53
references.pmid: 11255176
references.citation: Biotechnol Prog. 2004 Nov-Dec;20(6):1797-801
references.pmid: 15575714
references.citation: Pharm Res. 2003 Jul;20(7):1055-62
references.pmid: 12880292
references.citation: Ann Biomed Eng. 2003 Dec;31(11):1383-401
references.pmid: 14758929
references.citation: J Control Release. 2006 Jan 10;110(2):400-407
references.pmid: 16325953
references.citation: Osteoarthritis Cartilage. 2007 Feb;15(2):187-97
references.pmid: 16965923
references.citation: Biomaterials. 2007 Jan;28(3):475-85
references.pmid: 16996127
references.citation: Biomaterials. 2002 Feb;23(4):1169-85
references.pmid: 11791921
references.citation: Biotechnol Prog. 1998 Jan-Feb;14(1):108-15
references.pmid: 9496675
references.citation: J Microencapsul. 2006 Feb;23(1):15-27
references.pmid: 16830974
references.citation: J Biomech Eng. 2003 Apr;125(2):161-8
references.pmid: 12751277
references.citation: Tissue Eng. 2007 Aug;13(8):2003-10
references.pmid: 17518722
references.citation: J Exp Med. 1962 Mar 1;115:453-66
references.pmid: 13872176
references.citation: Biomaterials. 2005 May;26(14):1935-43
references.pmid: 15576167
references.citation: Biotechnol Bioeng. 2006 Apr 20;93(6):1130-7
references.pmid: 16444737
references.citation: J Control Release. 2007 Aug 16;121(1-2):100-9
references.pmid: 17604870
references.citation: J Control Release. 2005 Jan 3;101(1-3):111-25
references.pmid: 15588898
references.citation: Biomaterials. 2005 Jun;26(16):3227-34
references.pmid: 15603817
references.citation: Pharm Res. 2003 Aug;20(8):1103-12
references.pmid: 12948005
references.citation: Tissue Eng. 2006 Feb;12(2):267-78
references.pmid: 16548685
references.citation: Science. 1993 May 14;260(5110):920-6
references.pmid: 8493529
references.citation: J Control Release. 2001 May 18;73(1):59-74
references.pmid: 11337060
references.citation: Tissue Eng. 2001 Dec;7(6):767-80
references.pmid: 11749733
references.citation: J Bone Miner Res. 2002 Feb;17(2):221-30
references.pmid: 11811552
references.citation: Biomaterials. 2004 Dec;25(27):5821-30
references.pmid: 15172494
references.citation: Biorheology. 2003;40(1-3):299-306
references.pmid: 12454419
references.citation: J Biomed Mater Res A. 2007 Oct;83(1):1-9
references.pmid: 17335022
references.citation: Exp Cell Res. 1999 Mar 15;247(2):543-53
references.pmid: 10066382
references.citation: Int J Pharm. 2003 Apr 30;256(1-2):153-60
references.pmid: 12695021
references.citation: Tissue Eng. 2004 Nov-Dec;10(11-12):1787-95
references.pmid: 15684687
references.citation: J Biomed Mater Res A. 2005 Oct 1;75(1):156-67
references.pmid: 16052490
references.citation: Biomaterials. 2002 Jan;23(2):551-9
references.pmid: 11761175
references.citation: J Mater Sci Mater Med. 2006 Nov;17(11):1049-56
references.pmid: 17122918
references.citation: J Biomed Mater Res A. 2006 Feb;76(2):264-71
references.pmid: 16265648
references.citation: J Biomech Eng. 2001 Apr;123(2):198-200
references.pmid: 11340882
references.citation: J Biomech. 2004 Mar;37(3):375-82
references.pmid: 14757457