title: Nanofiber scaffolds with gradients in mineral content for spatial control of osteogenesis.
abstract: Reattachment of tendon to bone has been a challenge in orthopedic surgery. The disparate mechanical properties of the two tissues make it difficult to achieve direct surgical repair of the tendon-to-bone insertion. Healing after surgical repair typically does not regenerate the natural attachment, a complex tissue that connects tendon and bone across a gradient in both mineral content and cell phenotypes. To facilitate the regeneration of the attachment, our groups have developed a nanofiber-based scaffold with a graded mineral coating to mimic the mineral composition of the native tendon-to-bone insertion. In the present work, we evaluated the ability of this scaffold to induce graded osteogenesis of adipose-derived mesenchymal stem cells (ASCs). Results from 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferating cell nuclear antigen staining indicated that cell proliferation was negatively correlated with the mineral content. In contrast, alkaline phosphatase staining, an indicator of osteogenesis, was positively correlated with the mineral content. Likewise, runt-related transcription factor 2 (an early marker of osteoblast differentiation) and osteocalcin (a late marker of osteoblast differentiation) immunostaining were both positively correlated with the mineral content. These results indicate that a gradient in mineral content on the surface of a nanofiber scaffold is capable of inducing graded differentiation of ASCs into osteoblasts for enthesis repair.
authors.affiliation: School of Chemical and Biomolecular Engineering, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
authors.forename: Wenying
authors.initials: W
authors.lastname: Liu
authors.forename: Justin
authors.initials: J
authors.lastname: Lipner
authors.forename: Jingwei
authors.initials: J
authors.lastname: Xie
authors.forename: Cionne N
authors.initials: CN
authors.lastname: Manning
authors.forename: Stavros
authors.initials: S
authors.lastname: Thomopoulos
authors.forename: Younan
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D008855:Microscopy, Electron, Scanning; D008903:Minerals / Q000032:analysis*; D057139:Nanofibers; D010012:Osteogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D054457:Tissue Scaffolds
chemical_list: D008903:Minerals