Research & Initiatives
CNTE lab has been actively involved in various research initiatives to understand the underlying mechanisms of neurodegenerative diseases and develop effective treatments. The lab's research efforts span several fields, including Computational modelling, synthetic chemistry, post-processing, and in vitro and in vivo validation.
One of the key research areas at CNTE is the development of nanostructured scaffolds for tissue engineering applications. The lab has developed innovative scaffold designs that mimic the extracellular matrix of the nervous system, allowing for the growth and regeneration of damaged tissue.
CNTE's research and initiatives demonstrate its commitment to advancing neurodegenerative disease research and developing effective treatments for patients. The lab's multidisciplinary approach, innovative research methods, and collaborations with industry partners and other institutions are immensely contributing to the scientific community.
Computational Biomodelling
Self-assembling peptides (SAPs) and peptide nucleic acids (PNAs) are two types of biomolecules that have gained considerable attention in recent years due to their unique properties, such as self-assembly, biocompatibility, and biodegradability. These biomolecules have the potential to be used in various applications, including tissue engineering, drug delivery, and biosensing.
Our research aims to develop computational models to predict the self-assembly behaviour of SAPs and PNAs, as well as to investigate the properties of the resulting biomaterials. By using molecular dynamics simulations and other computational techniques, we can study the interactions between these biomolecules and predict their behaviour at the molecular level.
One of our key research projects involves the development of a predictive model for the self-assembly of SAPs and PNAs. This model is based on the principles of molecular recognition and self-assembly, and it can be used to design new SAPs and PNAs with specific properties.
Another project focuses on the design of SAP-based hydrogels for tissue engineering applications. By using computational models to predict the self-assembly behaviour of SAPs, we can design hydrogels with specific properties, such as mechanical strength, porosity, and biocompatibility.
Overall, our lab is committed to advancing the field of computational biomodelling of self-assembling peptides and peptide nucleic acids. By developing new computational approaches and collaborating with industry partners, we hope to accelerate the development of novel biomaterials with exciting new applications.
Synthetic Chemistry
Over the last decade, there has been an increasing interest in regenerative medicine as the “ultimate” therapy for damaged tissues or organs. Among the different approaches, the use of self-assembling peptides (SAPs) has become a leading strategy in regenerative medicine. Indeed, SAPs provide several advantages, including relative ease of synthesis, tuneability, optimal biocompatibility, bioabsorbility and lastly, non-immunogenicity. Moreover, they can display different functional motifs interacting with cells and proteins involved in cell signalling, thus making them biomimetic. Commonly, SAPs form ordered nano-assemblies in water at concentrations of 1–5% (w/v), yielding interwoven nanofibers capable of forming hydrogels upon exposure to external shifts in pH, temperature, or salts. In particular, SAPs containing alternating hydrophilic and hydrophobic amino acid residues (e.g. RADA16, or LDLK3) have enabled pioneering works across a number of different applications.
Although these rationally designed supramolecular nanomaterials offer unquestionable advantages as hemostat solutions, nanocarriers of drugs, bone fillers, wound healers, and injectable scaffolds for the regeneration of injured heart, cartilage and nucleus pulpous, they still face some limitations, like poor mechanical compliance, stiffness and elasticity. Those biomechanical limitations, being a consequence of the non-covalent interactions that mainly drive the self-assembly phenomenon, should be overcome to more accurately tune SAP properties and enlarge the number of their possible applications in tissue engineering (TE).
Being particularly interested on, CNTE introduced chemical cross-linking of SAPs as a new strategy leading to high-performance SAPs, named cross-SAPs, processable into self-standing scaffolds. Thanks to the improved biomechanics of cross-SAPs, our laboratories managed, for the first time, to electrospun cross-linked SAPs into resilient microchannels with tunable functionalization, flexibility and bioabsorption times to suit the specific needs of different applications.
The current interests of CNTE are developing new cross-linking strategies, and the synthesis of resilient peptide materials, aimed to improve the low elastic profiles of bulk materials. Moreover, CNTE is a partner of the SynEry project, a Horizon European program (grant agreement No 101046894), whose remarkably ambitious goal is providing a scalable, on-demand artificial blood substitute, via design of a Synthetic Erythrocyte facsimile. To this aim, the role of CNTE is synthesising SAPs combining their unique properties with the peculiar characteristics of peptide nucleic acids (PNAs).
Post-Processing Technology
The Center for Nanomedicine and Tissue Engineering (CNTE) has been working here on a variety of methods to improve implantable scaffolds as cell, drug, and enzyme supporters. Over a couple of years, CNTE is working with two major techniques Electrospinning and 3-D printing for the post-processing of SAPs.
Electrospinning is a voltage-driven, fabrication process governed by a specific electrohydrodynamic phenomenon where small fibres are yielded from a polymer solution or melt. The spinning process takes place when a high electric potential between two electrodes (needle tip and collector) of opposite polarities is exerted. Once the electrostatic repulsion resulting from charge accumulation at the surface of the injected solution overcomes the surface tension of polymer solution, or melts, allowing Taylor Cone formation and subsequently jet ejection toward the collector that eventually generates solid fibres as the solvent evaporates.
3D bioprinting has emerged as a promising new approach for fabricating complex biological constructs in the field of tissue engineering and regenerative medicine. It aims to alleviate the hurdles of conventional tissue engineering methods by precise and controlled layer-by-layer assembly of biomaterials in a desired 3D pattern.
Presently, our research focuses on translational projects directed towards the development of regenerative medicine, scaffolding and drug delivery based on 2D and 3D electrospun and microfluidic 3D bio-printed scaffolds made up of self-assembling peptides for spinal cord injury regeneration. Successful demonstration of the electrospun SAPs lamina and microchannels filled by neural stem cells is one of our recent accomplishments, which reveals an appropriate implant to restore chronic spinal cord injury.
3D Cell Culture and Organoids
3D cell cultures provide an unparalleled platform to recreate spatial arrangements in which cells, under proper conditions, can grow, differentiate, and interact with the surrounding extracellular matrix. CNTE group intends to generate an advanced 3D cell culture system, named organoid, with specific cellular organization, resembling a precise tract of the nervous tissue, including brain regions and/or spinal cord tracts. The resulting construct could be a powerful model for drug discovery, and toxicology, as well as advanced tools for neural tissue engineering and regenerative medicine. CNTE innovative approaches rely on the idea of generating and standardising fully-synthetic constructs, composed of synthetic self-assembling peptides biomaterials and organized human neural stem cells (hNSCs) able to generate an electrically active neural network.
SAP-based bioprostheses for nervous regeneration
The brain, spinal cord, and peripheral nerves are delicate structures that form the nervous system (NS), and unfortunately due to the intricate texture, the NS is vulnerable to a variety of injuries usually permanent and incapacitating.
Patients with severe NS injuries such as spinal cord injury (SCI), traumatic brain injury (TBI) or stroke may require lifelong therapy, placing a tremendous strain on patients, their families, and society. Innovative, paradigm-shifting approaches are needed to improve neurological injury therapy. For that reason, CNTE neuroregeneration research is at the vanguard of NS healing. CNTE neuroscientists, engineers and other specialists are employing a multidisciplinary integrative approach to neuroregeneration for SCI. The research is broad, spanning from basic science discovery to pre-clinical applications
