TY - JOUR
T1 - The use of three-dimensional nanostructures to instruct cells to produce extracellular matrix for regenerative medicine strategies
AU - Schenke-Layland, Katja
AU - Rofail, Fady
AU - Heydarkhan, Sanaz
AU - Gluck, Jessica M.
AU - Ingle, Nilesh P.
AU - Angelis, Ekaterini
AU - Choi, Chang Hwan
AU - MacLellan, William R.
AU - Beygui, Ramin E.
AU - Shemin, Richard J.
AU - Heydarkhan-Hagvall, Sepideh
PY - 2009/9
Y1 - 2009/9
N2 - 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(ε-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.
AB - 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(ε-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.
KW - Biomimetic material
KW - ECM
KW - Electrospinning
KW - Multiphoton imaging
KW - Nanotopography
KW - Tissue engineering
UR - http://www.scopus.com/inward/record.url?scp=67749139451&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67749139451&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2009.05.033
DO - 10.1016/j.biomaterials.2009.05.033
M3 - Article
C2 - 19524289
AN - SCOPUS:67749139451
SN - 0142-9612
VL - 30
SP - 4665
EP - 4675
JO - Biomaterials
JF - Biomaterials
IS - 27
ER -