A Hyaluronic Acid Demilune Scaffold and Polypyrrole-Coated Fibers Carrying Embedded Human Neural Precursor Cells and Curcumin for Surface Capping of Spinal Cord Injuries

Autores de CIPF

• Hoda Atef Sabri Ali Elkhenany

  Autor

• Pablo Bonilla Villamil

  Autor

• 

  Esther Giraldo Reboloso

  Autor

• Ana Alastrue Agudo

  Autor

• 

  Maria Jesus Vicent Docon

  Autor

• 

  M Victoria Moreno Manzano

  Autor

Participantes ajenos a CIPF

• Edel, MJ
• Roca, FG
• Ramos, CM
• Doblado, LR
• Pradas, MM

Grupos de Investigación

• Laboratorio de Polímeros Terapéuticos

  

  Jefe/a de Grupo

  Maria Jesus Vicent Docon

• Laboratorio de Regeneración Tisular y Neuronal

  

  Jefe/a de Grupo

  M Victoria Moreno Manzano

Abstract

Tissue engineering, including cell transplantation and the application of biomaterials and bioactive molecules, represents a promising approach for regeneration following spinal cord injury (SCI). We designed a combinatorial tissue-engineered approach for the minimally invasive treatment of SCI-a hyaluronic acid (HA)-based scaffold containing polypyrrole-coated fibers (PPY) combined with the RAD16-I self-assembling peptide hydrogel (Corning(R) PuraMatrix (TM) peptide hydrogel (PM)), human induced neural progenitor cells (iNPCs), and a nanoconjugated form of curcumin (CURC). In vitro cultures demonstrated that PM preserves iNPC viability and the addition of CURC reduces apoptosis and enhances the outgrowth of Nestin-positive neurites from iNPCs, compared to non-embedded iNPCs. The treatment of spinal cord organotypic cultures also demonstrated that CURC enhances cell migration and prompts a neuron-like morphology of embedded iNPCs implanted over the tissue slices. Following sub-acute SCI by traumatic contusion in rats, the implantation of PM-embedded iNPCs and CURC with PPY fibers supported a significant increase in neuro-preservation (as measured by greater beta III-tubulin staining of neuronal fibers) and decrease in the injured area (as measured by the lack of GFAP staining). This combination therapy also restricted platelet-derived growth factor expression, indicating a reduction in fibrotic pericyte invasion. Overall, these findings support PM-embedded iNPCs with CURC placed within an HA demilune scaffold containing PPY fibers as a minimally invasive combination-based alternative to cell transplantation alone.

Keywords

• spinal cord injury; PuraMatrix hydrogel; hyaluronic acid; biomaterials; induced neural progenitor cells; curcumin