Evaluation of early and late effects into the acute spinal cord injury of an injectable functionalized self-assembling scaffold.

Abstract

The complex physiopathological events occurring after spinal cord injury (SCI) make this devastating trauma still incurable. Self-assembling peptides (SAPs) are nanomaterials displaying some appealing properties for application in regenerative medicine because they mimic the structure of the extra-cellular matrix (ECM), are reabsorbable, allow biofunctionalizations and can be injected directly into the lesion. In this study we evaluated the putative neurorigenerative properties of RADA16-4G-BMHP1 SAP, proved to enhance in vitro neural stem cells survival and differentiation. This SAP (RADA16-I) has been functionalized with a bone marrow homing motif (BMHP1) and optimized via the insertion of a 4-glycine-spacer that ameliorates scaffold stability and exposure of the biomotifs. We injected the scaffold immediately after contusion in the rat spinal cord, then we evaluated the early effects by semi-quantitative RT-PCR and the late effects by histological analysis. Locomotor recovery over 8 weeks was assessed using Basso, Beattie, Bresnahan (BBB) test. Gene expression analysis showed that at 7 days after lesion the functionalized SAP induced a general upregulation of GAP-43, trophic factors and ECM remodelling proteins, whereas 3 days after SCI no remarkable changes were observed. Hystological analysis revealed that 8 weeks after SCI our scaffold increased cellular infiltration, basement membrane deposition and axon regeneration/sprouting within the cyst. Moreover the functionalized SAP showed to be compatible with the surrounding nervous tissue and to at least partially fill the cavities. Finally SAP injection resulted in a statistically significant improvement of both hindlimbs' motor performance and forelimbs-hindlimbs coordination. Altogether, these results indicate that RADA16-4G-BMHP1 induced favourable reparative processes, such as matrix remodelling, and provided a physical and trophic support to nervous tissue ingrowth. Thus this biomaterial, eventually combined with cells and growth factors, may constitute a promising biomimetic scaffold for regenerative applications in the injured central nervous system.

• Authors: Daniela Cigognini, Alessandro Satta, Bianca Colleoni, Diego Silva, Matteo Donegà, Stefania Antonini, Fabrizio Gelain
• Journal: PloS one (PLoS One) Vol. 6 Issue 5 Pg. e19782 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 21611127 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptides
• RADA16-I

Topics

• Acute Disease
• Amino Acid Motifs
• Amino Acid Sequence
• Animals
• Chronic Disease
• Extracellular Matrix (drug effects, metabolism)
• Female
• Fluorescent Antibody Technique
• Gene Expression Regulation (drug effects)
• Injections
• Molecular Sequence Data
• Motor Activity (drug effects)
• Neovascularization, Pathologic (complications, pathology)
• Nerve Fibers (drug effects, pathology)
• Peptides (chemistry, pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Spinal Cord Injuries (complications, genetics, physiopathology, therapy)
• Tissue Scaffolds (chemistry)