Novel Tissue-Engineered Multimodular Hyaluronic Acid-Polylactic Acid Conduits for the Regeneration of Sciatic Nerve Defect.

The gold standard for the treatment of peripheral nerve injuries, the autograft, presents several drawbacks, and engineered constructs are currently suitable only for short gaps or small diameter nerves. Here, we study a novel tissue-engineered multimodular nerve guidance conduit for the treatment of large nerve damages based in a polylactic acid (PLA) microfibrillar structure inserted inside several co-linear hyaluronic acid (HA) conduits. The highly aligned PLA microfibers provide a topographical cue that guides axonal growth, and the HA conduits play the role of an epineurium and retain the pre-seeded auxiliary cells. The multimodular design increases the flexibility of the device. Its performance for the regeneration of a critical-size (15 mm) rabbit sciatic nerve defect was studied and, after six months, very good nerve regeneration was observed. The multimodular approach contributed to a better vascularization through the micrometrical gaps between HA conduits, and the pre-seeded Schwann cells increased axonal growth. Six months after surgery, a cross-sectional available area occupied by myelinated nerve fibers above 65% at the central and distal portions was obtained when the multimodular device with pre-seeded Schwann cells was employed. The results validate the multi-module approach for the regeneration of large nerve defects and open new possibilities for surgical solutions in this field.

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

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® PuraMatrix™ 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 ßIII-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.