Regenerative medicine

A scheme which summarizes approaches (i.e. spinning and biofactories) to produce artificial biocompatible and biodegradable fibres for tissue engineering applications.
A scheme which summarizes approaches (i.e. spinning and biofactories) to produce artificial biocompatible and biodegradable fibres for tissue engineering applications.

Regenerative medicine is a branch of translational research in tissue engineering and molecular biology which deals with the process of replacing, engineering or regenerating cells, tissues or organs to restore or establish normal function. At NANOTEC we aim to regenerate damaged tissues by combining cells from the body with highly porous biodegradable scaffolds, which act as templates for tissue regeneration. We also use powerful state of the art techniques to study the bone-tissue regeneration mechanism

Smart Materials for Regenerative Medicine

Current regenerative medicine strategies are mainly focused on the design of improved biomaterials that are non-immunogenic, biocompatible, and biodegradable, and can be functionalized with bioactive proteins and chemicals. Our research is based on alternative approach to produce biomaterials that mimic the extracellular matrix (ECM). For instance artificial biocompatible and biodegradable fibrous extracellular matrices are realized using a variety of natural and synthetic polymers in order to increase cell proliferation and cell adhesion. Another approach involves freeze-dried 3D porous collagen–chitosan scaffolds which are functionalized with protease-responsive capsules loaded with growth factors for guiding and controlling the release of selected bioactive agents that work in concert with the implants.

In association with Maastricht University (Prof. L. Moroni; http://www.moronilab.org/), several biofabrication technologies are also being developed to create smart constructs and direct cell fate. The core activities of the group evolve around acquiring and implementing knowledge for biofabrication technologies based on the following research objectives: (i) develop biofabrication technologies based on additive manufacturing and spinning, and bottom-up methodologies; (ii) integrate neural and vascular cues on current tissue regeneration strategies; (iii) engineer the immune response of biomaterials and biomedical devices.

Biofactories

Another alternative emerging approach involves biomaterials produced by the cells themselves in response to a chemical stimulus. Indeed, we exploited living cells as factories to produce new, functional and intelligent fibrils for tissue engineering, through the aid of synthetic dyes which spontaneously penetrate the membrane of living cells.

Plasma processing of scaffolds for tissue engineering

Plasma processing of scaffolds for tissue engineering can be used mainly to: 1) functionalize the scaffold surface in order to improve, when necessary, its hydrophilic character (i.e. transport of metabolites and waste products through water); 2) produce graded chemical composition from the top to the scaffold’s core to enhance cell colonization of the whole scaffold; 3) “decorate” the scaffold’s surface with biomimetic coatings containing proteins or ceramics (i.e. hydroxyapatite or magnesium) that resembles the natural tissue composition. On the other hand the application of plasma directly on cells or on cell culture media (plasma medicine) should promote a selective improvement of cell proliferation on 3D porous scaffolds stimulating in turn the regeneration of new tissue.

In association with Maastricht University (Prof. L. Moroni), we aim at engineering functional biomaterials to create 3D scaffolds able to control cell fate. This challenge is approached through a biomimetic design inspired by cell niches. Several strategies are being pursued, comprising smart coatings (e.g. layer-by-layer technology), chemical functionalization (e.g. covalent vs dynamic binding), and physical modification of surface properties (e.g. stiffness vs topography).

Left: Micro-CT of plasma modified polycaprolacton (PCL) scaffolds; fluorescent microscopy images (centre) and SEM scan of SAOS-2 cells grown on plasma modified PCL scaffold
Left: Micro-CT of plasma modified polycaprolacton (PCL) scaffolds; fluorescent microscopy images (centre) and SEM scan of SAOS-2 cells grown on plasma modified PCL scaffold

Bone-tissue engineering

A deeper comprehension of the biomineralization process is at the basis of tissue engineering and will be instrumental to the further development of regenerative medicine. The achievement of a complete and exhaustive explanation of a process as complex as biomineralization requires the synergy of different advanced experimental techniques. In this framework, we have developed a multi-scale approach–based on different complementary X-ray experimental techniques coupled to new analytical tools, which provide structural and morphological information on the engineered tissues, from the atomic to the micrometric scale. In particular we study the mechanism of mineralized matrix deposition in a tissue engineering approach in which bone tissue is formed when porous ceramic constructs are loaded with bone marrow stromal cells and implanted in vivo.
High resolution X-ray Phase contrast Tomography (XPCT) provides the 3D spatial distribution of the different tissues participating to the biomineralization process; Scanning X-ray micro diffraction (XRmD) exploits the focused sub-micrometer X-ray beam to achieve atomic information with high spatial resolution. Scanning through the beam the organic–inorganic interface, within a porous scaffold of the sample, we are able to distinguish and monitor the evolution of the different ‘players’ of the regeneration process (Collagen, Organic Matrix, Hydroxy Apatite (HA), amorphous calcium phosphate (ACP)). X-ray Fluorescence (XRF) verifies the chemical evolution of the different growing phases and investigates the distribution of Ca in the regenerated bone. This multi-technique approach provides information on the first steps of biomineralization: we investigate the precursor of the biomineralization, the ACP working as a Ca reservoir, the dynamics of the collagen which is anisotropically distributed far from the scaffold interface but strongly packed at the organic–inorganic interface. When Ca ions are sequestered inside the collagen gaps, the mineralization starts to develop and bone nanoparticles appear at the scaffold interface.
To monitor the relation between bone formation and vascularization, it is important to achieve a detailed imaging and a quantitative description of the complete three-dimensional vascular network in such constructs. We imaged the 3D vascularization network inside the scaffold, without any sample sectioning and preparation. This study of angiogenesis in tissue engineering is crucial for the evaluation of the performance of an artificially implanted construct. Indeed the control of the angiogenesis of the micro-vascular network with proper spatial organization is a key step to obtain tissue regeneration and repair.

(above) Sample preparation of engineered bone tissue: harvesting of cells from animal, differentiation of BMSC, seeding on the scaffold, implantation on the animal. (below) Analysis of the engineered bone by XPCT and by XRmD.

Facilities & Labs

Characterization Lab @ Lecce

Bio Lab @ Lecce

Toma Lab @ Rome

Bio Lab @ URT Bari

Plasma Technologies Lab @ URT Bari

Chemical-Structural Characterization Lab @ URT Bari

People

Laura_BlasiLaura

Blasi

CNR Researcher

Barbara_CorteseBarbara

Cortese

CNR Researcher

Loretta_delMercatoLoretta L.

del Mercato

CNR Researcher

Ilaria_PalamaIlaria E.

Palamà

CNR Researcher

michelaMichela

Fratini

CNR Researcher

scoles

Giacinto

Scoles

Emeritus Professor

Alessandra_QuartaAlessandra

Quarta

CNR Researcher

cedolaAlessia

Cedola

CNR Researcher

innaInna

Bukreeva

CNR Researcher

Eloisa_SardellaEloisa

Sardella

CNR Researcher

fabrizioFabrizio

Bardelli

Associate Researcher

Pietro-FaviaPietro

Favia

Associate Professor

Roberto_GristinaRoberto

Gristina

CNR Researcher

Lorenzo_MoroniLorenzo

Moroni

Associate Professor

lorenzo_3Lorenzo

Massimi

CNR PostDoc

brun_2Francesco

Brun

CNR PostDoc

 

Publications

  1. F. Spano, A. Quarta, C. Martelli, L. Ottobrini, R. R.M.  Rossi, G. Gigli, L. Blasi, Fibrous scaffolds fabricated by emulsion electrospinning: from hosting capacity to in vivo biocompatibility. Nanoscale, 8: 9293-9303, 2016. ISSN: 2040-3364; doi: 10.1039/c6nr00782a
  2. I. E. Palamà, F. Di Maria, S. D’Amone, G. Barbarella, G. Gigli Biocompatible and biodegradable fluorescent microfibers physiologically secreted by live cells upon spontaneous uptake of thiophene fluorophore. G. Journal of Materials Chemistry B, 3, 151- 158 (2015). ISSN: 2050-750X; doi: 10.1039/c4tb01562b.
  3. G. Ciasca, M. Papi, L. Businaro, G. Campi, M. Ortolani, V. Palmieri, A. Cedola, A. De Ninno, A. Gerardino, G. Maulucci, M. De Spirito Recent advances in superhydrophobic surfaces and their relevance to biology and medicine. Bioinspiration & biomimetics 11 (1), 011001, 2016. ISSN: 2050-750X; doi:10.1088/1748-3190/11/1/011001.
  4. F. Intranuovo, R. Gristina, L. Fracassi, L. Lacitignola, A. Crovace, P. Favia; Plasma processing of scaffolds for tissue engineering and regenerative medicine. Plasma Chemistry and Plasma Processing, 36, (2016) 269-280, ISSN: 02724324, doi: 10.1007/s11090-015-9667-0
  5. M. Fratini, G. Campi, I. Bukreeva, D. Pelliccia, M. Burghammer, G. Tromba, R. Cancedda, M. Mastrogiacomo, A. Cedola. X-ray micro-beam techniques and phase contrast tomography applied to biomaterials. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 364, 93-97, 2015. ISSN: 0168-583X; doi: 10.1016/j.nimb.2015.06.023.
  6. G. Campi, M. Fratini, I. Bukreeva, G. Ciasca, M. Burghammer, F. Brun, G. Tromba, M. Mastrogiacomo, A. Cedola. Imaging collagen packing dynamics during mineralization of engineered bone tissue Acta biomaterialia, 23, 309-316 (2015). ISSN: 1742-7061; doi: 10.1016/j.actbio.2015.05.033.
  7. I. Bukreeva, M. Fratini, G. Campi, D. Pelliccia, R. Spanò, F. Brun, M. Burghammer, M. Grilli, R. Cancedda, A. Cedola, M. Mastrogiacomo High-resolution X-ray techniques as new tool to investigate the 3D vascularization of engineered-bone tissue. Frontiers in bioengineering and biotechnology, 3, 133 (2015).ISSN: 2296-4185; doi:10.3389/fbioe.2015.00133
  8. E. Sardella, E. R. Fisher, J. C. Shearer, M. Garzia Trulli, R. Gristina, P. Favia, N2/H2O Plasma Assisted Functionalization of Poly(ε-caprolactone) Porous Scaffolds: Acidic/Basic Character versus Cell Behavior, Plasma Process. Polym. 12-8, 786-798 (2015); ISSN: 16128850, doi: 10.1002/ppap.201400201
  9. I. Trizio, F. Intranuovo, R. Gristina, G. Dilecce, P. Favia, He/O2 atmospheric pressure plasma jet treatments of PCL scaffolds for tissue engineering and regenerative medicine. Plasma Processes and Polymers 12-12, 1451-1458 (2015) , ISSN: 16128850, doi: 10.1002/ppap.201500104
  10. I. Trizio, E. Sardella, E. Francioso, G. Dilecce, V. Rizzi, P. Cosma, M. Schmidt, M. Hansch, T. von Woedtke, P. Favia, R. Gristina, Investigation of air-DBD effects on biological liquids for in vitro studies on eukaryotic cells, Clinical Plasma Medicine 3-2, 62-71 (2015) ISSN: 22128166, doi: 10.1016/j.cpme.2015.09.003
  11. F. Intranuovo, R. Gristina, F. Brun, S. Mohammadi, G. Ceccone, E. Sardella, F.Rossi, G. Tromba, P. Favia, Plasma modification of PCL porous scaffolds fabricated by solvent-casting/particulate-leaching for tissue engineering, Plasma Process. Polym. 11, 184–195 (2014), ISSN: 16128850, doi: 10.1002/ppap.201300149
  12. R. Spano, I. Bukreeva, G. Campi, G. Tromba, F. Brun, A. Cedola, R. Cancedda, M. Mastrogiacomo Vascular network visualization in bone tissue engineered construct by synchrotron X-ray microtomography. Journal of tissue engineering and regenerative medicine 8, 211-211 (2014). ISSN: 1932-6254;
  13. Campi, I. Bukreeva, M. Fratini, M. Mastrogiacomo, A. Cedola Imaging tissue regeneration/degeneration by combined X-ray micro-diffraction and phase contrast micro-tomography. In Journal of tissue engineering and regenerative medicine 8, 66-67, 2014. ISSN: 1932-6254;

Other selected publications

  1. I. E. Palamà, F. Di Maria, I. Viola, E. Fabiano, G. Gigli, C. Bettini, G. Barbarella. Live-cell-permeant thiophene fluorophores and cell-mediated formation of fluorescent fibrils. Journal of the American Chemical Society (JACS), 133, 17777–17785 (2011). ISSN: 0002-7863; doi: 10.1021/la2065522
  2. I. Viola, I. E. Palamà, A. M. L. Coluccia, M. Biasiucci, B. Dozza, E. Lucarelli, C. Bettini, G. Barbarella, G. Gigli Physiological formation of fluorescent and conductive protein microfibers in live fibroblasts upon spontaneous uptake of biocompatible fluorophores. Integrative Biology, 5, 1057- 1066, 2013. ISSN: 1757-9694; doi: 10.1039/c3ib40064f.
  3. G. Campi, G. Pezzotti, M. Fratini, A. Ricci, M. Burghammer, R. Cancedda, I. Bukreeva, M. Mastrogiacomo, A. Cedola, Imaging regenerating bone tissue based on neural networks applied to micro-diffraction measurements. Applied Physics Letters,103 (25), 253703 (2013) ISSN: 0003-6951; doi: 10.1063/1.4852056
  4. G. Campi, A. Ricci, A. Guagliardi, C. Giannini, S. Lagomarsino, R. Cancedda, M. Mastrogiacomo, A. Cedola. Early stage mineralization in tissue engineering mapped by high resolution X-ray microdiffraction. Acta biomaterialia,8(9), 3411-3418. 2012 ISSN: 1742-7061; doi: 10.1016/j.actbio.2012.05.034.
  5. A. Guagliardi, A. Cedola, C. Giannini, M. Ladisa, A. Cervellino, A. Sorrentino, S. Lagomarsino, R. Cancedda, M. Mastrogiacomo. Debye function analysis and 2D imaging of nanoscaled engineered bone. Biomaterials, 31(32), 8289-8298 (2010). ISSN: 0142-9612; doi: 10.1016/j.biomaterials.2010.07.051
  6. M. Domingos, F. Intranuovo, A. Gloria, R. Gristina, L. Ambrosio, P.J. Bartolo, P. Favia, Improved osteoblast cell affinity on plasma modified 3-D extruded PCL scaffolds. Acta Biomaterialia 9-4, 5997-6005 (2013) ISSN: 1742-7061; doi: 10.1016/j.actbio.2012.12.031
  7. R. Cancedda, A. Cedola, A. Giuliani, V. Komlev, S. Lagomarsino, M. Mastrogiacomo, F. Peyrin, F. Rustichelli. Bulk and interface investigations of scaffolds and tissue-engineered bones by X-ray microtomography and X-ray microdiffraction. Biomaterials, 28(15), 2505-2524 (2007). ISSN: 0142-9612; doi: 10.1016/j.biomaterials.2007.01.022
  8. M. Mastrogiacomo, A. Papadimitropoulos, A. Cedola, F. Peyrin, P. Giannoni, S. G. Pearce, M. Alini, C. Giannini, A. Guagliardi, R. Cancedda Engineering of bone using bone marrow stromal cells and a silicon-stabilized tricalcium phosphate bioceramic: evidence for a coupling between bone formation and scaffold resorption. Biomaterials, 28(7), 1376-1384 (2007). ISSN: 0142-9612; doi: 10.1016/j.biomaterials.2006.10.001
  9. V. S. Komlev, F. Peyrin, M. Mastrogiacomo, A. Cedola, A. Papadimitropoulos, F. Rustichelli, R. Cancedda, Kinetics of in vivo bone deposition by bone marrow stromal cells into porous calcium phosphate scaffolds: an X-ray computed microtomography study. Tissue engineering, 12(12), 3449-3458, 2006. ISSN: 1076-3279; doi: 10.1089/ten.2006.12.3449
  10. A. Cedola, M. Mastrogiacomo, S. Lagomarsino, R. Cancedda, C. Giannini, A. Guagliardi, M. Ladisa, M. Burghammer, F. Rustichelli, V. Komlev, Orientation of mineral crystals by collagen fibers during in vivo bone engineering: an X-ray diffraction imaging study Spectrochimica Acta Part B: Atomic Spectroscopy, 62(6), 642-647,2007. ISSN: 0584-8547; doi: 10.1016/j.sab.2007.02.015

Awards

1. Special mention to Eloisa Sardella during the competition “Italia Camp-your idea for the country (la tua idea per il paese)” during the BarCamp “ Stati Generali del Mezzogiorno d’Europa” with the idea titled “plasma3D” 2012

Project

  1. NaBiDiT – Nano-Biotecnologie per Diagnostica e sviluppo di Terapie innovative; Regional project APQ Ricerca Scientifica—Reti di Laboratori Pubblici di Ricerca – (2010-2012)
  2. MAGNIFYCO – Magnetic nanocontainers for combined hyperthermia and controlled drug release; Project ID: 228622 – FP7-NMP (2009-2013)
  3. RINOVATIS – Rigenerazione di tessuti nervosi ed osteocartilaginei mediante innovativi approcci di Tissue Engineering, MIUR-PON Grant PON02_00563_3448479, 2013-2015, Alessandro Sannino (coordinator), P. Favia

Latest News

Loretta del Mercato, si aggiudica l'ERC STARTING GRANT 2017

Loretta del Mercato, si aggiudica  l'ERC STARTING GRANT 2017

uno dei bandi più competitivi a livello europeo.

Lecce, 6 settembre 2017 

Lo European Research Council, che promuove la ricerca di eccellenza in Europa, nei giorni scorsi ha reso noti i nomi dei 406 vincitori della selezione ERC STARTING GRANT 2017, il bando tra i più competitivi a livello internazionale.

Su 3085 progetti presentati, 406 i progetti selezionati a cui sono stati destinati i 605 i milioni di euro di investimento. 48 le nazioni di provenienza dei ricercatori, soltanto 17 gli Italiani che condurranno le loro ricerche nel nostro paese, tra cui Loretta del Mercato, ricercatrice dell'Istituto di Nanotecnologia del Consiglio Nazionale delle Ricerche di Lecce.

Un importante riconoscimento alla ricerca nel settore della medicina di precisione condotta presso il CNR NANOTEC, un indiscusso premio al talento della giovane ricercatrice che, a 38 anni e un contratto a tempo determinato, sarà a capo del progetto "Sensing cell-cell interaction heterogeneity in 3D tumor models: towards precision medicine – INTERCELLMED".

Il progetto, il cui obiettivo è affrontare uno dei problemi più spinosi della ricerca sul cancro, ovvero la difficoltà nel trasformare i risultati delle ricerche scientifiche in applicazioni cliniche per i pazienti e che vedrà coinvolto l'Istituto tumori "Giovanni Paolo II" di Bari, si propone di sviluppare nuovi modelli in vitro 3D di tumore del pancreas, alternativi ai modelli animali, ingegnerizzati con un set di sensori nanotecnologici che consentiranno di monitorare le interazioni delle cellule tumorali con il loro micorambiente, verificare l'appropriatezza delle terapie prima della somministrazione ai pazienti oncologici e quindi prevedere la risposta dei singoli pazienti ad una o più terapie antitumorali.

La realizzazione di queste piattaforme 3D multifunzionali consentirà di superare le evidenti differenze intercorrenti tra "modelli animali" ed esseri umani fornendo dati attendibili ed in tempi più rapidi rispetto ai dati ottenuti tramite lunghi e costosi procedimenti di sperimentazione sugli animali. Le tecnologie e i modelli sviluppati saranno estesi anche ad altre forme di tumori solidi nonché impiegati per studi nell'ambito della ingegneria tissutale e della medicina rigenerativa.

Rassegna stampa e Video

Zeiss Microscopy Technology and Complete Correlative Workflow

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Zeiss Microscopy Technology and Complete Correlative Workflow

Lecce, Italy, 2017 Wednesday July 19th 

CNR NANOTEC @ Lecce, Aula Seminari – pal. G, Piano Terra

Program - PDF

Zeiss, as microscopy technology leader, provides the unique complete imaging solution ranging from light, confocal, electron, ion and Xray modalities with a complete and straightforward correlative workflow. An overview of different technologies will be presented with a special focus on X-Rray microscopy.

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MCS 2017

International Workshop on Micropropulsion and CubeSats

Bari, Italy, 26 - 27 June 2017

Program - MSC2017

This narrow-field, invited-only meeting is the first attempt to bring together the Materials and Micropropulsion communities with a view to contribute to the development of the Global Materials and Micropropulsion Roadmap, and set such meetings to a regular basis.