Format

Send to

Choose Destination
Tissue Eng Part A. 2016 Feb;22(3-4):306-17. doi: 10.1089/ten.TEA.2015.0422.

Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair.

Author information

1
1 Institute of Experimental Medicine AS CR , Prague, Czech Republic .
2
2 2nd Medical Faculty, Charles University , Prague, Czech Republic .
3
3 Department of Neuroscience, Norwegian University of Science and Technology , Trondheim, Norway .
4
4 John Van Geest Centre for Brain Repair, School of Clinical Neurosciences, University of Cambridge , Cambridge, United Kingdom .
5
5 Division of Pharmacology and Clinical Neuroscience, Department of Neurosurgery, Umeå University , Umeå, Sweden .
6
6 McGowan Institute for Regenerative Medicine , Pittsburgh, Pennsylvania.

Abstract

Restoration of lost neuronal function after spinal cord injury (SCI) still remains a big challenge for current medicine. One important repair strategy is bridging the SCI lesion with a supportive and stimulatory milieu that would enable axonal rewiring. Injectable extracellular matrix (ECM)-derived hydrogels have been recently reported to have neurotrophic potential in vitro. In this study, we evaluated the presumed neuroregenerative properties of ECM hydrogels in vivo in the acute model of SCI. ECM hydrogels were prepared by decellularization of porcine spinal cord (SC) or porcine urinary bladder (UB), and injected into a spinal cord hemisection cavity. Histological analysis and real-time qPCR were performed at 2, 4, and 8 weeks postinjection. Both types of hydrogels integrated into the lesion and stimulated neovascularization and axonal ingrowth into the lesion. On the other hand, massive infiltration of macrophages into the lesion and rapid hydrogel degradation did not prevent cyst formation, which progressively developed over 8 weeks. No significant differences were found between SC-ECM and UB-ECM. Gene expression analysis revealed significant downregulation of genes related to immune response and inflammation in both hydrogel types at 2 weeks post SCI. A combination of human mesenchymal stem cells with SC-ECM did not further promote ingrowth of axons and blood vessels into the lesion, when compared with the SC-ECM hydrogel alone. In conclusion, both ECM hydrogels bridged the lesion cavity, modulated the innate immune response, and provided the benefit of a stimulatory substrate for in vivo neural tissue regeneration. However, fast hydrogel degradation might be a limiting factor for the use of native ECM hydrogels in the treatment of acute SCI.

PMID:
26729284
PMCID:
PMC4799710
DOI:
10.1089/ten.TEA.2015.0422
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center