title: Composite scaffolds: bridging nanofiber and microsphere architectures to improve bioactivity of mechanically competent constructs.
abstract: Tissue engineering often benefits from the use of composites to produce an ideal scaffold. We present the focused development of a novel structure that combines the biomimetic properties of nanofibers with the robust mechanical aspects of the sintered microsphere scaffold to produce a composite scaffold that demonstrates an ability to mimic the mechanical environment of trabecular bone while also promoting the phenotype progression of osteoblast progenitor cells. These composite nanofiber/microsphere scaffolds exhibited a mechanical modulus and compressive strength similar to trabecular bone and exhibited degradation resulting in a mass loss of 30% after 24 weeks. The nanofiber portion of these scaffolds was sufficiently porous to allow cell migration throughout the fibrous portion of the scaffold and promoted phenotype progression through focal adhesion kinase-mediated activation of the transcription factor Runx2, control scaffolds not containing nanofibers did not demonstrate extensive cell migration or phenotype progression. Ultimately, the focal adhesion kinase activity on the composite nanofiber/microsphere scaffolds demonstrated causality over the production of the mature osteoblast marker, osteocalcin, and the development of a calcified matrix.
authors.affiliation: Department of Bioengineering, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Brown
authors.forename: M Sean
authors.initials: MS
authors.lastname: Peach
authors.forename: Lakshmi S
authors.initials: LS
authors.lastname: Nair
authors.forename: Sangamesh G
authors.initials: SG
authors.lastname: Kumbar
authors.forename: Cato T
authors.initials: CT
authors.lastname: Laurencin
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D008422:Materials Testing; D055595:Mechanical Phenomena / Q000187:drug effects*; D051379:Mice; D008863:Microspheres; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D010641:Phenotype; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D015415:Biomarkers; D050659:Core Binding Factor Alpha 1 Subunit; D051416:Focal Adhesion Protein-Tyrosine Kinases