Biologic scaffolds composed of central nervous system extracellular matrix

Peter M. Crapo, Christopher J. Medberry, Janet E. Reing, Stephen Tottey, Yolandi van der Merwe, Kristen E. Jones, Stephen F. Badylak

Research output: Contribution to journalArticlepeer-review

155 Scopus citations

Abstract

Acellular biologic scaffolds are commonly used to facilitate the constructive remodeling of three of the four traditional tissue types: connective, epithelial, and muscle tissues. However, the application of extracellular matrix (ECM) scaffolds to neural tissue has been limited, particularly in the central nervous system (CNS) where intrinsic regenerative potential is low. The ability of decellularized liver, lung, muscle, and other tissues to support tissue-specific cell phenotype and function suggests that CNS-derived biologic scaffolds may help to overcome barriers to mammalian CNS repair. A method was developed to create CNS ECM scaffolds from porcine optic nerve, spinal cord, and brain, with decellularization verified against established criteria. CNS ECM scaffolds retained neurosupportive proteins and growth factors and, when tested with the PC12 cell line in vitro, were cytocompatible and stimulated proliferation, migration, and differentiation. Urinary bladder ECM (a non-CNS ECM scaffold) was also cytocompatible and stimulated PC12 proliferation but inhibited migration rather than acting as a chemoattractant over the same concentration range while inducing greater rates of PC12 differentiation compared to CNS ECM. These results suggest that CNS ECM may provide tissue-specific advantages in CNS regenerative medicine applications and that ECM scaffolds in general may aid functional recovery after CNS injury.

Original languageEnglish (US)
Pages (from-to)3539-3547
Number of pages9
JournalBiomaterials
Volume33
Issue number13
DOIs
StatePublished - May 2012

Bibliographical note

Funding Information:
This work was supported in part by the NIH ( 5R01AR053603 ), an Ocular Tissue Engineering and Regenerative Ophthalmology (OTERO) Fellowship from the Louis J. Fox Center for Vision Restoration (a joint program of UPMC and the University of Pittsburgh), and an NIBIB training grant ( T32EB001026 ). The authors also thank Deanna Rhoads for histologic sectioning and Chris Carruthers for experimental assistance.

Keywords

  • Central nervous system
  • Decellularization
  • Extracellular matrix
  • Regenerative medicine
  • Scaffolds
  • Tissue engineering

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