title: The use of three-dimensional nanostructures to instruct cells to produce extracellular matrix for regenerative medicine strategies.
abstract: Synthetic polymers or naturally-derived extracellular matrix (ECM) proteins have been used to create tissue engineering scaffolds; however, the need for surface modification in order to achieve polymer biocompatibility and the lack of biomechanical strength of constructs built using proteins alone remain major limitations. To overcome these obstacles, we developed novel hybrid constructs composed of both strong biosynthetic materials and natural human ECM proteins. Taking advantage of the ability of cells to produce their own ECM, human foreskin fibroblasts were grown on silicon-based nanostructures exhibiting various surface topographies that significantly enhanced ECM protein production. After 4 weeks, cell-derived sheets were harvested and histology, immunochemistry, biochemistry and multiphoton imaging revealed the presence of collagens, tropoelastin, fibronectin and glycosaminoglycans. Following decellularization, purified sheet-derived ECM proteins were mixed with poly(epsilon-caprolactone) to create fibrous scaffolds using electrospinning. These hybrid scaffolds exhibited excellent biomechanical properties with fiber and pore sizes that allowed attachment and migration of adipose tissue-derived stem cells. Our study represents an innovative approach to generate strong, non-cytotoxic scaffolds that could have broad applications in tissue regeneration strategies.
authors.affiliation: Cardiovascular Research Laboratories, Department of Medicine/Cardiology, David Geffen School of Medicine, 675 Charles E Young Dr. South, MRL-3579, Los Angeles, CA 90095, USA. kschenkelayland@mednet.ucla.edu
authors.forename: Katja
authors.initials: K
authors.lastname: Schenke-Layland
authors.forename: Fady
authors.initials: F
authors.lastname: Rofail
authors.forename: Sanaz
authors.initials: S
authors.lastname: Heydarkhan
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Gluck
authors.forename: Nilesh P
authors.initials: NP
authors.lastname: Ingle
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Angelis
authors.forename: Chang-Hwan
authors.initials: CH
authors.lastname: Choi
authors.forename: William R
authors.initials: WR
authors.lastname: MacLellan
authors.forename: Ramin E
authors.initials: RE
authors.lastname: Beygui
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Shemin
authors.forename: Sepideh
authors.initials: S
authors.lastname: Heydarkhan-Hagvall
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D001681:Biological Assay; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005453:Fluorescence; D006801:Humans; D049329:Nanostructures / Q000737:chemistry*; D017785:Photons; D011091:Polyesters / Q000494:pharmacology; D016062:Porosity / Q000187:drug effects; D044968:Regenerative Medicine / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D054457:Tissue Scaffolds
chemical_list: D016326:Extracellular Matrix Proteins; D011091:Polyesters; C016240:polycaprolactone