The use of three-dimensional nanostructures to instruct cells to produce extracellular matrix for regenerative medicine strategies

Katja Schenke-Layland, Fady Rofail, Sanaz Heydarkhan, Jessica M. Gluck, Nilesh P. Ingle, Ekaterini Angelis, Chang Hwan Choi, William R. MacLellan, Ramin E. Beygui, Richard J. Shemin, Sepideh Heydarkhan-Hagvall

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)4665-4675
Number of pages11
Issue number27
StatePublished - Sep 2009
Externally publishedYes

Bibliographical note

Funding Information:
The authors would like to thank Prof. Chang-Jin Kim (Department of Mechanical and Aerospace Engineering, UCLA) for providing the nanostructures. This work was supported by the NIH 5T32HL007895-10 (K.S-L.) and the Department of Surgery at UCLA. Confocal laser scanning microscopy was performed at the CNSI Advanced Light Microscopy/Spectroscopy Shared Resource Facility at UCLA, supported with funding from NIH-NCRR shared resources grant (CJX1-443835-WS-29646) and NSF Major Research Instrumentation grant (CHE-0722519).


  • Biomimetic material
  • ECM
  • Electrospinning
  • Multiphoton imaging
  • Nanotopography
  • Tissue engineering


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