Improved Recovery of Complete Spinal Cord Transection by a Plasma-Modified Fibrillar Scaffold.

Complete spinal cord injury causes an irreversible disruption in the central nervous system, leading to motor, sensory, and autonomic function loss, and a secondary injury that constitutes a physical barrier preventing tissue repair. Tissue engineering scaffolds are presented as a permissive platform for cell migration and the reconnection of spared tissue. Iodine-doped plasma pyrrole polymer (pPPy-I), a neuroprotective material, was applied to polylactic acid (PLA) fibers and implanted in a rat complete spinal cord transection injury model to evaluate whether the resulting composite implants provided structural and functional recovery, using magnetic resonance (MR) imaging, diffusion tensor imaging and tractography, magnetic resonance spectroscopy, locomotion analysis, histology, and immunofluorescence. In vivo, MR studies evidenced a tissue response to the implant, demonstrating that the fibrillar composite scaffold moderated the structural effects of secondary damage by providing mechanical stability to the lesion core, tissue reconstruction, and significant motor recovery. Histologic analyses demonstrated that the composite scaffold provided a permissive environment for cell attachment and neural tissue guidance over the fibers, reducing cyst formation. These results supply evidence that pPPy-I enhanced the properties of PLA fibrillar scaffolds as a promising treatment for spinal cord injury recovery.

Pyrrole Plasma Polymer-Coated Electrospun Scaffolds for Neural Tissue Engineering.

Promising strategies for neural tissue engineering are based on the use of three-dimensional substrates for cell anchorage and tissue development. In this work, fibrillar scaffolds composed of electrospun randomly- and aligned-oriented fibers coated with plasma synthesized pyrrole polymer, doped and undoped with iodine, were fabricated and characterized. Infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction analysis revealed the functional groups and molecular integration of each scaffold, as well as the effect of plasma polymer synthesis on crystallinity. Scanning microscopy imaging demonstrated the porous fibrillar micrometric structure of the scaffolds, which afforded adhesion, infiltration, and survival for the neural cells. Orientation analysis of electron microscope images confirmed the elongation of neurite-like cell structures elicited by undoped plasma pyrrole polymer-coated aligned scaffolds, without any biochemical stimuli. The MTT colorimetric assay validated the biocompatibility of the fabricated composite materials, and further evidenced plasma pyrrole polymer-coated aligned scaffolds as permissive substrates for the support of neural cells. These results suggest plasma synthesized pyrrole polymer-coated aligned scaffolds are promising materials for tissue engineering applications.

Pyrrole Plasma Polymer-Coated Fibrillar Scaffold Implant: Pilot Study in Rat Spinal Cord Transection with MRI.

Despite extensive research on spinal cord injury (SCI) therapies for the recovery of motor, sensory and autonomic function, currently there are no effective treatments to completely restore tissue structure and function. In this work, a polylactic acid (PLA) fibrillar scaffold coated with pyrrole plasma polymer doped with iodine (pPPy/I), was studied as therapeutic strategy in a SCI transection model. Magnetic resonance imaging (MRI) was used to evaluate tissue response to the implant. Behavioral analysis using the BBB open-field testing was conducted to evaluate functional response. MRI analysis showed the SCI model completely disrupted tissue continuity, and diffusion indices were altered at the injury site. The animals had completely paralyzed hindlimbs and bladder control loss after injury. After 8 weeks of treatment, in contrast to control and PLA-implanted animals, PLA+pPPy/I-implanted animal had regained bladder control autonomy and frequent to consistent weight supported plantar steps and occasional coordination between forelimbs and hindlimbs. These results suggest fibrillar scaffolds coated with pPPy/I constitute a promising therapy for SCI.

Feasibility of in vivo quantitative magnetic resonance imaging with diffusion weighted imaging, T2-weighted relaxometry, and diffusion tensor imaging in a clinical 3 tesla magnetic resonance scanner for the acute traumatic spinal cord injury of rats: technical note.

STUDY DESIGN: Prospective longitudinal study. OBJECTIVE: To verify the feasibility of performing in vivo quantitative magnetic resonance imaging evaluation of moderate traumatic spinal cord injury (SCI) in rats using a clinical 3T scanner. SUMMARY OF BACKGROUND DATA: Animal models of human diseases are essential for translational medicine. Potential treatments of SCI are evaluated in 2 ways: anatomical and functional. Advanced magnetic resonance sequences allow a noninvasive assessment of the spinal cord depicting both. This study describes and validates a very reproducible, feasible, affordable, and reliable method, designed to be applied in commercial 3T equipment, using a novel stereotactic device for spinal cord, leading to a readily available assessment of the progression of damage generated after traumatic SCI in rats. METHODS: Four Long-Evans female rats were injured with a New York University weight-drop device to produce the SCI by contusion at thoracic level 10. All animals were placed in a fixation system, using a commercial wrist antenna to obtain magnetic resonance imaging data of the relaxometry time, apparent diffusion coefficient, and fractional anisotropy. Three sets of data obtained before SCI and 1 and 4 weeks after injury were compared. RESULTS: The data showed a progressive decline in fractional anisotropy measurements after SCI comparing baseline versus the 1-week period (P < 0.001) and baseline versus the 4-week period (P < 0.019), with a significant progressive increase in apparent diffusion coefficient values and T2 after SCI only in the baseline versus the 4-week period (P < 0.045 and P < 0.024, respectively). CONCLUSION: Our results helped us to validate a novel method to acquire highly reproducible and reliable quantitative biomarkers of traumatic SCI in vivo by using a 3T clinical MR scanner coupled with a novel stereotactic device for rats. LEVEL OF EVIDENCE: N/A.