Results

Results

Mat2Rep  is aimed to develop new pharmacological agents in two therapeutic areas: A. the acute phase of traumatic and vascular lesions of the central nervous system (CNS); B. chronic non healing skin ulcers.
The design and manufacturing of the new products requires the convergence of chemical, pharmaceutical, biotechnology and material science competences.

 

Therapeutic area A: acute phase of traumatic and vascular CNS lesions

Two design strategies are adopted:

1) electroconductive materials to improve CNS repair;

2) biomaterial-assisted drug delivery.

Strategy 1: a hydrogel-based electroconductive material has been developed by the ISTEC-CNR lab and characterized for its mechanical and conductive properties. The material is under testing using primary cultures of cortical neurons by the CIRI-SDV (UNIBO), facing and overcoming imaging and bio-compatibility issues. Functional monitoring will be carried out by MISTER, using electronic devices based on organic and inorganic (Au/SiNws) materials for the extracellular recording of electrophysiological signals in a non-invasive way.

Strategy 2: multifunctional biodegradable nanoparticles have been produced by the UNIMORE lab, aimed to deliver a mix of drugs (ibuprofen, T3 and erythropoietin) on the injured site, optimizing the encapsulation method, stability, release control, chemical-physical and morphological characteristics. Nanoparticles are under testing at CIRI-SDV and IRET for biocompatibility and efficacy

 

Therapeutic area B: chronic non healing skin ulcers

An integrin agonist has been selected and synthetized at CIRI-SDV (UNIBO), together with a molecule able to enhance wound healing (nerve growth factor – NGF). An electrospun polymer containing the molecule for the controlled drug release at the lesion site has been produced. Efficacy of the drug delivery system based on the electrospun polymer have been tested by the IRET lab on different cell types involved in ulcers response.

Publications

1) Saracino E, Cirillo V, Marrese M, Guarino V, Benfenati V, Zamboni R, Ambrosio L. Structural and Functional Properties of Astrocytes on PCL based electrospun fibres. Science and Eng. C. 2020, 118, 111363. Doi: https://doi.org/10.1016/j.msec.2020.111363

2) Duskey JT, Baraldi C, Gamberini MC, Ottonelli I, Da Ros F, Tosi G, Forni F, Vandelli MA, Ruozi B. Investigating Novel Syntheses of a Series of Unique Hybrid PLGA-Chitosan Polymers for Potential Therapeutic Delivery Applications. Polymers 2020, 12, 823. Doi: https://doi.org/10.3390/polym12040823

3) Saracino E, Maiolo L, Polese D, Semprini M, Borrachero-Conejo AI, Gasparetto J, Murtagh S, Sola M, Tomasi L, Valle F, Pazzini L, Formaggio F, Chiappalone M, Hussain S, Caprini M, Muccini M, Ambrosio L, Fortunato G, Zamboni R, Convertino A, Benfenati V. A glial-silicon nanowire electrode junction enabling differentiation and non invasive recording of slow oscillations from astrocytes. 2020, 4, 1900264. Doi: https://doi.org/10.1002/adbi.201900264

4) Oddone N, Boury F, Garcion E, Grabrucker AM, Martinez MC, Da Ros F, Janaszewska A, Forni, Vandelli MA, Tosi G, et al. Synthesis, Characterization, and In Vitro Studies of an Reactive Oxygen Species (ROS)-Responsive Methoxy Polyethylene Glycol-Thioketal-Melphalan Prodrug for Glioblastoma Treatment. Pharmacol. 2020, 11. Doi: https://doi.org/10.3389/fphar.2020.00574

5) Birolini G, Valenza M, Ottonelli I, Passoni A, Favagrossa M, Duskey JT, Bombaci M, Vandelli MA, Colombo L, Bagnati R, et al. Insights into Kinetics, Release, and Behavioral Effects of Brain-Targeted Hybrid Nanoparticles for Cholesterol Delivery in Huntington’s Disease. Journal of Controlled Release 2021, 330, 587–598. Doi: https://doi.org/10.1016/j.jconrel.2020.12.051

6) Ottonelli I, Duskey JT, Rinaldi A, Grazioli MV, Parmeggiani I, Vandelli MA, Wang LZ, Prud’homme RK, Tosi G, Ruozi B. Microfluidic Technology for the Production of Hybrid Nanomedicines. 2021 Sep 17;13(9):1495. doi: 10.3390/pharmaceutics13091495.

7) Saracino E, Zuppolini S, Guarino V, Benfenati V, Borriello A, Zamboni R, Ambrosio L. Polyaniline nano-needles into electrospun bio active fibres support in vitro astrocyte response. RSC Adv. 2021, 11, 11347-11355. Doi: 1039/d1ra00596k

8) Maiolo L, V. Guarino V, Saracino E, Convertino A, Melucci M, Muccini M, Ambrosio L, Zamboni R, Benfenati V. Glial interfaces: advanced materials and devices to uncover the role of astroglial cells in brain functions and dysfunctions. Healthcare Mater. 2021, 1, 2001268. Doi: https://doi.org/10.1002/adhm.202001268

9) Bighinati A, Khalajzeyqami Z, Baldassarro VA, Lorenzini L, Cescatti M, Moretti M, Giardino L, Calzà L. Time-Course Changes of Extracellular Matrix Encoding Genes Expression Level in the Spinal Cord Following Contusion Injury – A Data-Driven Approach. Int J Mol 2021, 22, 1744. Doi: https://doi.org/10.3390/ijms22041744.

10) Baldassarro VA, Sanna M, Bighinati A, Sannia M, Gusciglio M, Giardino L, Lorenzini L and Calzà L. A time course study of the expression level of synaptic plasticity-associated genes in un-lesioned spinal cord and brain areas in a rat model of spinal cord injury: a bioinformatic approach. IJMS, 2021, 22:8606-8629. Doi: https://doi.org/10.3390/ijms22168606

11) Alastra G, Aloe L, Baldassarro VA, Calzà L, Cescatti M, Duskey JT, Focarete ML, Giacomini D, Giardino L, Giraldi V, Lorenzini L, Moretti M, Parmeggiani I, Sannia M, Tosi G. Nerve Growth Factor Biodelivery: a limiting step in moving toward extensive clinical application?. Frontiers in NeuroScience 2021, https://doi.org/10.3389/fnins.2021.695592

12) Flagelli A, Candini O, Frabetti S, Dominici M, Giardino L, Calzà L, Baldassarro VA. A Novel Three-Dimensional Culture Device Favors a Myelinating Morphology of Neural Stem Cell-Derived Oligodendrocytes. Front Cell Dev Biol. 2021 Oct 1;9:759982. doi: 10.3389/fcell.2021.759982

13) Baldassarro VA. High-Content Screening Differentiation and Maturation Analysis of Fetal and Adult Neural Stem Cell-Derived Oligodendrocyte Precursor Cell Cultures. J Vis Exp. 2021 Mar 10;(169). doi: 10.3791/61988.

14) Baldassarro VA, Lorenzini L, Giuliani A, Cescatti MAlastra G, Pannella M, ImbimboBP, Villetti GCalzàL, Giardino L. Molecular mechanisms of skin wound healing in non-diabetic and diabetic mice in excision and pressure experimental wounds. Cell Tissue Res 2022 Jun; 388(3):595-613. doi: 10.1007/s00441-022-03624-x.

15) Rinaldi A, Caraffi R, Grazioli MV, Oddone N, Giardino L, Tosi G, Vandelli MA, Calzà L, Ruozi B, Duskey JT. Applications of the ROS-Responsive Thioketal Linker for the Production of Smart Nanomedicines.Polymers (Basel) 2022 Feb 11;14(4):687, doi: 10.3390/polym14040687.

16) Merlo B, Baldassarro VA, Flagelli A, Marcoccia R, Giraldi V, Focarete ML, Giacomini D, Iacono E. Peptide Mediated Adhesion to Beta-Lactam Ring of Equine Mesenchymal Stem Cells: A Pilot Study. Animals (Basel). 2022 Mar 15;12(6):734. doi: 10.3390/ani12060734. PMID: 35327131

17) Furlani F, Montanari M, Sangiorgi N, Saracino E, Campodoni E, Sanson A, Benfenati V, Tampieri A, Panseri S, Sandri M. Electroconductive and injectable hydrogels based on gelatin and PEDOT:PSS for mini-invasive approaches in nervous tissue regeneration.Biomaterials Science 2022. DOI: 10.1039/d2bm00116k.

18) Baldassarro VA, Giraldi V, GiulianiA, Moretti M, Pagnotta G, Flagelli A, Clavenzani P, Lorenzini L, Giardino L,  Focarete ML, Giacomini D, Calzà L. Poly(l-lactic acid) Scaffold Releasing an α4β1 Integrin Agonist Promotes Nonfibrotic Skin Wound Healing in Diabetic Mice. ACS Appl Bio Mater. 2023 Jan 16;6(1):296-308. doi: 10.1021/acsabm.2c00890

19) Baldassarro VA, Cescatti M. Rocco ML, Aloe L, Lorenzini L, Giardino L, Calzà L. Nerve growth factor promotes differentiation and protects the oligodendrocyte precursor cells from in vitro hypoxia/ischemia. Neurosci., 16 February 2023 Sec. Neurodevelopment, Volume 17 – 2023 | https://doi.org/10.3389/fnins.2023.1111170