Institute of Fundamental Technological Research
Polish Academy of Sciences

Partners

Marco Costantini

Sapienza University of Rome (IT)

Recent publications
1.  Cidonio G., Costantini M., Pierini F., Scognamiglio C., Agarwal T., Barbetta A., 3D printing of biphasic inks: beyond single-scale architectural control, Journal of Materials Chemistry C, ISSN: 2050-7526, DOI: 10.1039/d1tc02117f, Vol.9, No.37, pp.12489-12508, 2021

Abstract:
To date, Additive Manufacturing (AM) has come to the fore as a major disruptive technology embodying two main research lines – developing increasingly sophisticated printing technologies and new processable materials. The latter has fostered a tremendous leap in AM technological advancement, allowing 3D printing to play a central role in dictating the tailorable settings for material design. In particular, the manufacturing of three-dimensional (3D) objects with functional hierarchical porous structure is of the utmost importance for numerous research areas, including tissue engineering, catalysis, aerospace, environmental science, electrochemistry, energy and sound absorption and light engineering materials. Biphasic inks such as emulsions, foams, and solid dispersions represent viable templating systems to realise multiscale porosity. The combination of AM techniques and biphasic inks provide pivotal control over multiple levels of material structure and function, enabling the use of advanced materials with unprecedented 3D architectures as well as physical, chemical, and mechanical properties. The related potential benefits are significant, with functional perspectives for a wide variety of research fields. In this concise review, we provide an updated overview of the employment of biphase inks and show how they are adapted to different AM technologies or vice versa.

Affiliations:
Cidonio G. - other affiliation
Costantini M. - Sapienza University of Rome (IT)
Pierini F. - IPPT PAN
Scognamiglio C. - other affiliation
Agarwal T. - other affiliation
Barbetta A. - Sapienza University of Rome (IT)
2.  Rinoldi C., Zargarian S.S., Nakielski P., Li X., Liguori A., Petronella F., Presutti D., Wang Q., Costantini M., De Sio L., Gualandi C., Ding B., Pierini F., Nanotechnology-assisted RNA delivery: from nucleic acid therapeutics to COVID-19 vaccines, Small Methods, ISSN: 2366-9608, DOI: 10.1002/smtd.202100402, Vol.5, No.9, pp.2100402-1-49, 2021

Abstract:
In recent years, the main quest of science has been the pioneering of the groundbreaking biomedical strategies needed for achieving a personalized medicine. Ribonucleic acids (RNAs) are outstanding bioactive macromolecules identified as pivotal actors in regulating a wide range of biochemical pathways. The ability to intimately control the cell fate and tissue activities makes RNA-based drugs the most fascinating family of bioactive agents. However, achieving a widespread application of RNA therapeutics in humans is still a challenging feat, due to both the instability of naked RNA and the presence of biological barriers aimed at hindering the entrance of RNA into cells. Recently, material scientists’ enormous efforts have led to the development of various classes of nanostructured carriers customized to overcome these limitations. This work systematically reviews the current advances in developing the next generation of drugs based on nanotechnology-assisted RNA delivery. The features of the most used RNA molecules are presented, together with the development strategies and properties of nanostructured vehicles. Also provided is an in-depth overview of various therapeutic applications of the presented systems, including coronavirus disease vaccines and the newest trends in the field. Lastly, emerging challenges and future perspectives for nanotechnology-mediated RNA therapies are discussed.

Affiliations:
Rinoldi C. - IPPT PAN
Zargarian S.S. - IPPT PAN
Nakielski P. - IPPT PAN
Li X. - Donghua University (CN)
Liguori A. - University of Bologna (IT)
Petronella F. - other affiliation
Presutti D. - Institute of Physical Chemistry, Polish Academy of Sciences (PL)
Wang Q. - Donghua University (CN)
Costantini M. - Sapienza University of Rome (IT)
De Sio L. - Sapienza University of Rome (IT)
Gualandi C. - University of Bologna (IT)
Ding B. - Donghua University (CN)
Pierini F. - IPPT PAN
3.  Rinoldi C., Costantini M., Kijeńska-Gawrońska E., Testa S., Fornetti E., Heljak M., Ćwiklińska M., Buda R., Baldi J., Cannata S., Guzowski J., Gargioli C., Khademhosseini A., Święszkowski W., Tendon tissue engineering: effects of mechanical and biochemical stimulation on stem cell alignment on cell‐laden hydrogel yarns, ADVANCED HEALTHCARE MATERIALS, ISSN: 2192-2659, DOI: 10.1002/adhm.201801218, Vol.8, No.7, pp.1801218-1-10, 2019

Abstract:
Fiber-based approaches hold great promise for tendon tissue engineering enabling the possibility of manufacturing aligned hydrogel filaments that can guide collagen fiber orientation, thereby providing a biomimetic micro-environment for cell attachment, orientation, migration, and proliferation. In this study, a 3D system composed of cell-laden, highly aligned hydrogel yarns is designed and obtained via wet spinning in order to reproduce the morphology and structure of tendon fascicles. A bioink composed of alginate and gelatin methacryloyl (GelMA) is optimized for spinning and loaded with human bone morrow mesenchymal stem cells (hBM-MSCs). The produced scaffolds are subjected to mechanical stretching to recapitulate the strains occurring in native tendon tissue. Stem cell differentiation is promoted by addition of bone morphogenetic protein 12 (BMP-12) in the culture medium. The aligned orientation of the fibers combined with mechanical stimulation results in highly preferential longitudinal cell orientation and demonstrates enhanced collagen type I and III expression. Additionally, the combination of biochemical and mechanical stimulations promotes the expression of specific tenogenic markers, signatures of efficient cell differentiation towards tendon. The obtained results suggest that the proposed 3D cell-laden aligned system can be used for engineering of scaffolds for tendon regeneration.

Keywords:
hydrogel fibers, static mechanical stretching, stem cell alignment, tenogenic differentiation, wet spinning

Affiliations:
Rinoldi C. - other affiliation
Costantini M. - Sapienza University of Rome (IT)
Kijeńska-Gawrońska E. - Warsaw University of Technology (PL)
Testa S. - Tor Vergata Rome University (IT)
Fornetti E. - Tor Vergata Rome University (IT)
Heljak M. - Warsaw University of Technology (PL)
Ćwiklińska M. - Institute of Physical Chemistry, Polish Academy of Sciences (PL)
Buda R. - Institute of Physical Chemistry, Polish Academy of Sciences (PL)
Baldi J. - Tor Vergata Rome University (IT)
Cannata S. - Tor Vergata Rome University (IT)
Guzowski J. - Institute of Physical Chemistry, Polish Academy of Sciences (PL)
Gargioli C. - Tor Vergata Rome University (IT)
Khademhosseini A. - Massachusetts Institute of Technology (US)
Święszkowski W. - other affiliation
4.  Costantini M., Guzowski J., Żuk P.J., Mozetic P., De Panfilis S., Jaroszewicz J., Heljak M., Massimi M., Pierron M., Trombetta M., Dentini M., Święszkowski W., Rainer A., Garstecki P., Barbetta A., Electric Field Assisted Microfluidic Platform for Generation of Tailorable Porous Microbeads as Cell Carriers for Tissue Engineering, Advanced Functional Materials, ISSN: 1616-301X, DOI: 10.1002/adfm.201800874, Vol.28, pp.1800874-1-13, 2018

Abstract:
Injection of cell‐laden scaffolds in the form of mesoscopic particles directly to the site of treatment is one of the most promising approaches to tissue regeneration. Here, a novel and highly efficient method is presented for preparation of porous microbeads of tailorable dimensions (in the range ≈300–1500 mm) and with a uniform and fully interconnected internal porous texture. The method starts with generation of a monodisperse oil‐in‐water emulsion inside a flow‐focusing microfluidic device. This emulsion is later broken‐up, with the use of electric field, into mesoscopic double droplets, that in turn serve as a template for the porous microbeads. By tuning the amplitude and frequency of the electric pulses, the template droplets and the resulting porous bead scaffolds are precisely produced. Furthermore, a model of pulsed electrodripping is proposed that predicts the size of the template droplets as a function of the applied voltage. To prove the potential of the porous microbeads as cell carries, they are tested with human mesenchymal stem cells and hepatic cells, with their viability and degree of microbead colonization being monitored. Finally, the presented porous microbeads are benchmarked against conventional microparticles with nonhomogenous internal texture, revealing their superior performance.

Affiliations:
Costantini M. - Sapienza University of Rome (IT)
Guzowski J. - Institute of Physical Chemistry, Polish Academy of Sciences (PL)
Żuk P.J. - IPPT PAN
Mozetic P. - Università Campus Bio-Medico di Roma (IT)
De Panfilis S. - Sapienza Istituto Italiano di Tecnologia (IT)
Jaroszewicz J. - other affiliation
Heljak M. - Warsaw University of Technology (PL)
Massimi M. - University of L’Aquila (IT)
Pierron M. - Telecom Physique Strasbourg (FR)
Trombetta M. - Università Campus Bio-Medico di Roma (IT)
Dentini M. - Sapienza University of Rome (IT)
Święszkowski W. - other affiliation
Rainer A. - Università Campus Bio-Medico di Roma (IT)
Garstecki P. - Institute of Physical Chemistry, Polish Academy of Sciences (PL)
Barbetta A. - Sapienza University of Rome (IT)
5.  Celikkin N., Rinoldi C., Costantini M., Trombetta M., Rainer A., Święszkowski W., Naturally derived proteins and glycosaminoglycan scaffolds for tissue engineering applications, Materials Science and Engineering C-Materials for Biological Applications, ISSN: 0928-4931, DOI: 10.1016/j.msec.2017.04.016, Vol.78, pp.1277-1299, 2017

Abstract:
Tissue engineering (TE) aims to mimic the complex environment where organogenesis takes place using advanced materials to recapitulate the tissue niche. Cells, three-dimensional scaffolds and signaling factors are the three main and essential components of TE. Over the years, materials and processes have become more and more sophisticated, allowing researchers to precisely tailor the final chemical, mechanical, structural and biological features of the designed scaffolds. In this review, we will pose the attention on two specific classes of naturally derived polymers: fibrous proteins and glycosaminoglycans (GAGs). These materials hold great promise for advances in the field of regenerative medicine as i) they generally undergo a fast remodeling in vivo favoring neovascularization and functional cells organization and ii) they elicit a negligible immune reaction preventing severe inflammatory response, both representing critical requirements for a successful integration of engineered scaffolds with the host tissue. We will discuss the recent achievements attained in the field of regenerative medicine by using proteins and GAGs, their merits and disadvantages and the ongoing challenges to move the current concepts to practical clinical application.

Keywords:
Natural polymers, Hydrogel scaffolds, Glycosaminoglycans (GAGs), Fibrous proteins, Regenerative medicine

Affiliations:
Celikkin N. - Warsaw University of Technology (PL)
Rinoldi C. - other affiliation
Costantini M. - Sapienza University of Rome (IT)
Trombetta M. - Università Campus Bio-Medico di Roma (IT)
Rainer A. - Università Campus Bio-Medico di Roma (IT)
Święszkowski W. - other affiliation

List of chapters in recent monographs
1. 
Święszkowski W., Paradiso A., Volpi M., Rinoldi C., Idaszek J., Costantini M., Biofabrication: an integrated bioengineering approach for the automated fabrication of biological structures for clinical and research applications, rozdział: Mimicking nature with biofabrication, Pàtron, pp.31-50, 2021
2. 
Costantini M., Testa S., Rinoldi C., Celikkin N., Idaszek J., Colosi C., Gargioli C., Święszkowski W., Barbetta A., Biomaterials Science Series, Biofabrication and 3D Tissue Modeling, rozdział: 3D Tissue Modelling of Skeletal Muscle Tissue, Royal Society of Chemistry, Edited by Dong-Woo Cho, 3, pp.184-215, 2019

Category A Plus

IPPT PAN

logo ippt            Pawińskiego 5B, 02-106 Warsaw
  +48 22 826 12 81 (central)
  +48 22 826 98 15
 

Find Us

mapka
© Institute of Fundamental Technological Research Polish Academy of Sciences 2021