title: Three-dimensional poly(1,8-octanediol-co-citrate) scaffold pore shape and permeability effects on sub-cutaneous in vivo chondrogenesis using primary chondrocytes.
abstract: The objective of this study was to evaluate the coupled effects of three-dimensional poly(1,8-octanediol-co-citrate) (POC) scaffold pore shape and permeability on chondrogenesis using primary chondrocytes in vivo. Chondrogenesis was characterized as cartilage matrix formation by sulfated glycosaminoglycan (sGAG) quantification, relative mRNA expression of the cartilage-related proteins collagen types I, II and X, aggrecan and matrix metalloproteinases 13 and 3 and the compressive mechanical properties of the tissue/scaffold construct. A low permeability design with a spherical pore shape showed a significantly greater increase in cartilage matrix formation over 6 weeks in vivo than a high permeability design with a cubical pore shape. This increase in cartilage matrix synthesis corresponded with increases in mechanical compressive nonlinear elastic properties and histological data demonstrating darker red Safranin-O staining. There was higher mRNA expression for both cartilage-specific proteins and matrix degradation proteins in the high permeability design, resulting in overall less sGAG retained in the high permeability scaffold compared with the low permeability scaffold. Controlled POC scaffolds with a spherical pore shape and low permeability correlated with significantly increased cartilage matrix production using primary seeded chondrocytes. These results indicate that the low permeability design with a spherical pore shape provided a better microenvironment for chondrogenesis than the high permeability design with a cubical pore shape. Thus, scaffold architecture and material design may have a significant impact on the success of matrix-based clinical cartilage repair strategies.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-2125, USA.
authors.forename: Claire G
authors.initials: CG
authors.lastname: Jeong
authors.forename: Huina
authors.initials: H
authors.lastname: Zhang
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hollister
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects*; D002951:Citrates / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D055119:Elastic Modulus / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000378:metabolism; D008422:Materials Testing; D051379:Mice; D017711:Nonlinear Dynamics; D010539:Permeability / Q000187:drug effects; D011108:Polymers / Q000494:pharmacology*; D016062:Porosity / Q000187:drug effects; D019919:Prosthesis Implantation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical; D040521:Subcutaneous Tissue / Q000187:drug effects*; D034421:Sus scrofa; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D002951:Citrates; D006025:Glycosaminoglycans; D011108:Polymers; D012333:RNA, Messenger; C513817:poly(1,8-octanediol citrate); D004247:DNA