TY - JOUR
T1 - Biologic scaffolds composed of central nervous system extracellular matrix
AU - Crapo, Peter M.
AU - Medberry, Christopher J.
AU - Reing, Janet E.
AU - Tottey, Stephen
AU - van der Merwe, Yolandi
AU - Jones, Kristen E.
AU - Badylak, Stephen F.
N1 - 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.
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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.
KW - Central nervous system
KW - Decellularization
KW - Extracellular matrix
KW - Regenerative medicine
KW - Scaffolds
KW - Tissue engineering
UR - http://www.scopus.com/inward/record.url?scp=84857445186&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2012.01.044
DO - 10.1016/j.biomaterials.2012.01.044
M3 - Article
C2 - 22341938
AN - SCOPUS:84857445186
SN - 0142-9612
VL - 33
SP - 3539
EP - 3547
JO - Biomaterials
JF - Biomaterials
IS - 13
ER -