Neural Tissue Engineering

Worldwide, an estimated 2.5 million people live with spinal cord injury, with more than 130,000 new injuries reported each year. Spinal cord injury has a significant impact on patient quality of life, life expectancy and economic burden, with considerable costs associated with primary care and loss of income. Stroke is currently the second leading cause of death in the Western world, ranking after heart diseases and before cancer, and could raise secondary dysfunctions too.

In the case of focal brain ischemia and chronic spinal cord injuries, namely whenever an extensive loss of tissue occurs, cell therapy is helpful but not sufficient for the regeneration of the lost tissues. Within these regions, mechanical substrates are needed in order to provide physical support for axonal regeneration and for the transplanted cells to effectively integrate within the host tissues.

Tissue engineering is an interdisciplinary field of medical science that brings together the principles of material science, biochemistry, cell biology, physics and medical science, aiming to develop biological “components” for the maintenance, regeneration or replacement of tissues and organs.

In the typical approach of tissue engineering cells, harvested from biopsies or obtained from cell banks, are cultured in vitro for their expansion, then seeded into polymeric scaffolds and implanted into the damaged tissue. Additionally, scaffolds my be loaded with drugs to provide a short- or medium term delivery in vivo.

In neural tissue engineering some of used approaches comprise pro-regenerative drugs like neurotrophic factors, neuroprotective compounds, chemotactic cytokines and anti-inflammatory agents. Scaffolds are also seeded with myelinating cells (Schwann cells, Olfactory Ensheathing cells ), genetically modified cells secreting neurotrophic factors in vivo, and, most importantly, stem cells, both embrionic and neural stem cells, rapidly becoming the most tested candidates for nervous tissue replacements. Notably, in both peripheral and central nervous systems an effective regenerative approach has to address the spatial re-organization of the tissue to be regenerated, to be achieved via chemotactic attraction nad/or physical guidance of the regenerating nervous tissues.

Nanostructured Scaffolds

The success of neural tissue engineering therapies partially rely on the quality of transplanted cells engraftment and functional integration into the injured host tissues. In particular, cells are located in 3-dimensional (3D) microenvironments in vivo, where they are surrounded by other cells and by the extracellular matrix (ECM), whose components are organized mainly in nanostructures displaying specific bioactive motifs that regulate the cell homeostasis. It is therefore essential to develop scaffolds that create reproducible microenvironments in order to control and direct the cellular behavior and to promote specific cellular interactions.

Self-assembling peptides (Sapeptides) are made of short linear peptides, they are soluble and usually liquid when dissolved in water. They jellify when exposed to a triggering stimulus, that, in the case of sapeptides to be used in nanomedicine, could be a shift in temperature, pH, or hydrophobicity of the solvent. Cells can be mixed with sapeptide solutions prior self-assembling, and, can be embedded in true 3D substrates through subsequent gelation. By adopting the same peptide synthesis technique sapeptides can be quickly functionalized, and designed for specific biological applications: drug release, cell proliferation and survival, etc.

A technique that allows for the synthesis of nanostructured scaffolds with a designed spatial organization is electrospinning. This technique allows the fabrication of controllable continuous nanofiber scaffolds made of natural and synthetic polymers, or of inorganic substances.

By quickly customizing the standard electrospinning setup nanofibers can be collected to form hollow guidance channels, nonwoven mats with random directionality, or patches with radially oriented fibers.

Dr.Gelain research interests include design and characterization of novel functionalized sapeptides and electrospun scaffolds for tissue engineering applications and, in particular, for the regeneration of spinal cord injuries and stroke. His research, spanning from basic science to translational research, aims at the development of effective therapies in the fields of nervous regeneration and nanomedicine.

High-Performance Self-Assembling Peptides

Until recently, self-assembling peptides showed unquestionable promising biomimetic properties and high biocompatibility. However, most of the potential applications in tissue engineering and beyond were precluded because of their poor biomechanics, coming with their self-assembling propensity. Indeed, self-assembling usually involves weak transient non-covalent interactions that hardly allow for SAPs to display stiffness and viscosity suited for cartilage/bone tissue engineering and for electrospinning respectively. Dr.Gelain’s group successfully introduced branched molecules of SAPs and chemical cross-linkings as two possible new strategies to fill this gap. This opens up a plethora of new potential applications for SAPs, providing the missing point to finally exploit the self-assembling technology of peptides in tissue engineering, nanomedicine and likely other fields.