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1. Verify the in-house existence of MM parameters for non-natural AAs selected for peptide design/synthesis. Derive missing parameters by QM calculations
2. Define the most suitable computational protocol for the assigned task, also using specific benchmarks
3. Perform conformational studies on selected model peptides using classical MD and T-REMD or H-REMD
4. Perform in-silico aggregation studies using accelerated MD
5. Starting from the most promising sequences, according to the experimental results, new peptidomimetics will be designed
Beneficiary: UPC (9 Months)
Training on QM/MM techniques applied to aggregation studies
Simune (3 Months)
Training on QM/MM techniques applied to aggregation studies
1. A first generation of peptidomimetics will be prepared by using known non-standard AAs, mostly aromatic β-AAs or heterocyclic AAs (and according to the results on nanomaterials already achieved). New scaffolds will be developed according to computational feedback structure
2. AAs and peptides will be characterized by NMR, CD, IR, UV spectroscopy to define their secondary structure
3. Selected peptidomimetics for specific applications: i) electrospinning, peptidomimetics containing a heterocyclic nucleus; ii) self-assembly of electro-responsive peptides containing aromatic AAs as carriers for releasing of antimicrobial peptides. An iterative process will be repeated until an optimal lead nanomaterial has been identified
Beneficiary: UPC (9 Months)
Self-assembly of selected peptides containing aromatic substituents using different environmental conditions. Evaluation of the electrochemical and electrical response of the prepared hierarchical structures using cyclic voltammetry, chronoamperometry and electrochemical impedance spectroscopy. Polarization treatments on selected structure will be applied to enhance such response
Italfarmaco (3 Months)
Training on the scale-up of peptide synthesis and purification
1. Synthesis of hybrid self-assembling peptides by silylation of self-assembling peptides reported in the literature
2. Self-assembly/mineralization of hybrid peptides by the sol-gel process. The influence of the peptide sequence, the number and nature of silyl groups will be investigated. Addition of templating reagents during the sol-gel process will also be tested
3. Characterization of the structured materials (eg. nanotubes and nanofibres) and their mechanism of formation
4. 3D printing and electrospinning of the hybrid structured materials and/or the hybrid self-assembling peptides to access an extra level of structural complexity (nano- and micro-structured materials)
Beneficiary NANOGUNE (9 Months)
Electrospinning of hybrid self-assembling peptides
Simune (3 months)
Training on computational studies to elucidate the mechanism of self-assembly of the hybrid peptides
1. Synthesis of bioactive peptide motifs for cell adhesion and differentiation and their conjugation to biopolymers such as chitosan and hyaluronic acid
2. Synthesis of self-assembling peptides as non-covalent gelating agents
3. Optimization of the peptide sequences by using non-standard amino acids and cyclization tools
4. Self-assembly and gelation studies
5. Characterization of nanomaterials
6. Studies on 3D printability and toxicity evaluation on cell
Beneficiary: UM (9 months)
Evaluation of cell viability, 3D printability of the peptide decorated nanomaterials
Deloitte (3 months)
Training on technology transfer and performance
1. Electrospun fibres from selected peptides and peptide/polymer mixtures synthesized at UMIL, UM and HUJI
2. They will be imaged by spectroscopic methods in scanning modes, specifically FTIR, Raman, and (E)SEM (if required, wetSTEM)
3. Flat grafts will be prepared by combining 3D printing of biocompatible polymers with thin matrices of electrospun peptides, proteins or polymers. The latter are selected towards application in TEVGs
Beneficiary: UMIL (9 Months)
Synthesis/spectroscopic conformational analysis of peptides and peptidomimetics to be used for electrospinning
Bayer (3 Months)
Acquisitions of skills on quality related to production and registration
1. Determine the intrinsic and in solution energy landscape of small peptides using systematic QM-based studies
2. Characterization of nanomaterials (films and particles) using spectroscopic, microscopy and MEMS techniques
3. Develop models for the formation of peptide aggregates from different experimental conditions using advanced modelling methods
4. Analysis of the role of specific and non-specific intermolecular interactions, as well as determine the presence of cooperative and/or anti-cooperative effects, using QM/MM-MD with multiple active zones
Beneficiary: UMIL (9 Months)
Training in advanced MD methods applied to supramolecular structures
Edelweiss Connect (3 Months)
To perform in-silico toxicology studies on non-natural AAs/peptides/peptidomimetics relevant for the project
1. The self-assembly of peptides in electrospinning and in non-electrified jets (3D printing) will be investigated experimentally and correlated with theoretical guidelines based on peptide and solvent properties, and with simulations at UPC
2. The results will allow to prepare new bi/multi-layered electrospun flat grafts, which will be analysed by (environmental) SEM (in water vapor) and by local mechanical measurements (AFM indentation, force-distance data)
3. Peptide-decorated hydrogels will be characterized by a multimethod approach (AFM, Raman imaging, SEM) with a view to application in cell culture
Beneficiary: HUJI (9 Months)
Training on peptide assembly from solution, and on combined AFM/confocal microscopy imaging
Genepep (3 Months)
Training on scale-up peptide synthesis
1. Investigation of safe cross-linking strategies (i.e. genepin, EDC-NHS, HDACS, HMDI, etc.) of newly-synthetized spinnable peptides/peptidomimetics. To improve fibres stability in simulated physiological environment, mechanical strength and elastic behaviour
2. Electro-spun bilayered flat grafts will be prepared using biodegradable polymers (i.e. PLGA, PLA, PLA-PCL, DegraPol® provided by AbMedica S.p.A, etc.) in combination with selected newly synthetized peptides/peptidomimetics to increase their suitability for the specific application. Bi/multi-layered grafts will be also prepared combining electrospinning with 3D-printing (Nanogune)
3. Physico-chemical, mechanical and biological characterization of the obtained electro-spun flat grafts
4. Small calibre VGs preparation set-up and their morphological, mechanical, physical-chemical and biological characterization. Stability studies will be also performed
Beneficiary: NANOGUNE (9 Months)
To test combined techniques (electrospinning/3D printing) for grafts set-up
AbMedica S.p.a. (3 Months)
To test newly-synthetized spinnable peptides / DegraPol® coupling
1. Testing fibres formation by electrospinning of: i) DOPA-Phe-Phe-RGD; ii) selected newly-synthetized peptides functionalized with DOPA-Phe-Phe-RGD and fluorinated AAs
2. Evaluation of the contribution of compatible adjuvant polymers (i.e. PLA or PLA-PCL) to DOPA-Phe-Phe-RGD-/fluorinated AAs-peptides derivatives on fibres formation
3. Bi/multi-layered composite flat scaffolds preparation by electrospinning
4. Morphological, mechanical, biological and microbiological characterization of the composite flat grafts
5. Composite small calibre VGs preparation and their morphological, mechanical, physical-chemical and biological characterization. Stability and sterilization studies will be also performed
Beneficiary: HUJI (9 Months)
Microbiological tests on electro-spun flat grafts for evaluating the PBC efficacy to prevent bacterial contamination
DeLama spa (3 Months)
To gain specific expertise on sterilization with Hydrogen Peroxide under deep vacuum and zero air
1. Synthesis of hybrid hydrogels by introduction of triethoxysilanes onto biopolymers (chitosan/gelatin/hyaluronan) and bioactive peptides
2. Preparation of functional hybrid hydrogels by the sol-gel process
3. Characterization of the hydrogels: physico- chemical (mechanical properties, stability/degradation, swelling) and biological (cytotoxicity, cell adhesion, proliferation, differentiation)
4. Cell encapsulation within the hydrogels
5. 3D printing of the cell-laden hydrogels into multi-layer scaffolds
Beneficiary: UMIL (9 months)
Tuning of hydrogels performance by insertion of unnatural amino acids and/or molecular scaffolds
Lynxter (3 months)
3D printing optimisation
1. Synthesis of a peptide that prevents biofilm formation using natural or unnatural AAs
2. Coat biocompatible polymers to prevent bacterial contamination and encourage integration
3. Examine the adhesion and proliferation of mammalian cells and bacterial cells to these surfaces
Beneficiary: UM (9 Months)
Hydrogel preparation and coating with a peptide-based coating
Jacobacci&Partners (3 Months)
To gain specific expertise on intellectual properties in nanomaterials
1. Design and synthesis of peptides that will self-assemble into a coating that resist bacterial adhesion and contain specific amino acids that signal specific adhesion of muscle cells and endothelial cells
2. Self-assembly of the peptide-based coating on tissue engineered vascular grafts
3. Perform cell biology assay to determine the viability and proliferation of the cells
4. Determine the ability of the coating to serve as an anti-biofilm coating on the VGs
Beneficiary UNIPV (9 Months)
To coat VGs with synthesized peptides and perform biological characterization (cytocompatibility, proliferation)
Biobasic Europe s.r.l. (3 Months)
Tests for safety and efficiency evaluation
1. Development of controlled plasma treatments to transform insulating peptide structures into electro-responsive structures considering different atmospheres, pressures and powers
2. Characterization of the stable species generated by plasma treatment
3. Re-exploration of the electrospinning conditions forcing the formation of stable charged species at the surface
4. Characterization of the charged fibres
5. Electrostimulated release of antimicrobials from the previously electro-responsive carriers
Beneficiary UNIPV (9 Months)
Preparation of electrospun fibres and their transformation using plasma
Ponti (3 Months)
To analyse the results from the innovation point of view at both technical/industrial levels, prospecting the protection through the different available registration modalities: patents, utility models or industrial designs
©Copyright 2023
Università degli Studi di Milano
Via Festa del Perdono 7, 20122 Milano
Tel.+39 02 5032 5032 | Posta Elettronica Certificata
C.F. 80012650158 | P.I. 03064870151 | Codice LEI
©Copyright 2023
Università degli Studi di Milano
Via Festa del Perdono 7, 20122 Milano
Tel.+39 02 5032 5032
Posta Elettronica Certificata
C.F. 80012650158
P.I. 03064870151
Codice LEI
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