Bio-Hybrid Composites for Regenerative Medicine

Regeneration of multifunctional anatomical region

Principal investigators: Anna Tampieri, Monica Sandri
Personnel involved: Elisabetta Campodoni, Margherita Montanari, Chiara Artusi

The activity is dedicated to the development of biologically inspired processes producing hybrid multi-functional devices formed of nano-structured building blocks through bio-mineralization, self-assembling and self-organization. Implant for bone and osteochondral regeneration are developed, mimicking the physical-chemical-morphological characteristics of hard connective tissues (bone, cartilage, dentin, enamel, etc).

Thanks to the high level of biomimetism with natural biological tissues these scaffolds show high regenerative potential in vivo. On this basis several patents and commercial products have been developed (RegenOss® and MaioRegen®) and commercialized by Finceramica (born as ISTEC-CNR spin-off).

Bio-mineralization processes of hydroxyapatite nano-crystals with chemical-physical-structural bone-like characteristics were performed on auto-assembling Type-I collagen fibers. The final bio-hybrid composites perfectly mime the new-formed human bone. Compositionally and morphologically graded scaffolds are also developed in order to mimic the multifunctional anatomical regions.

Self-assembling polymeric blends (e.g. collagen, alginate, chitosan) are investigated to increase the mechanical performances as well as to modify the pore size and pore size distribution. Such parameters are modified also varying the cross linking agents (e.g. 1,4–butanediol diglycidyl ether, genipin, ribose and de-hydrothermal treatment) as well as the time and temperature of cross-linking in order to modulate the re-absorption kinetic and making it coherent with the regeneration and remodeling processes.

Equipment and processes

The synthesis of complex shaped devices, difficult to obtain by conventional fabrication techniques, is carried out by morpho-synthesis procedures in which macromolecular matrices are used as templates for heterogeneous nucleation of mineral phases. These techniques allow to create implants for bone and osteochondral regeneration, able to resemble the physical-chemical and morphological features of human hard connective tissues (bone, cartilage, dentine, enamel, etc).

Schematic process of Collagen mineralized with Mg-substituted hydroxyapatite

Main collaborations

Università degli studi di Torino, dipartimento di Chimica IFM;
Laboratoire d’evaluation des materiels implantables (LEMI);
FINCERAMICA Faenza S.p.A.;
Università Cattolica Sacro Cuore, Clinica Ortopedica;
Istituti Ortopedici Rizzoli;
Università di Bologna;
University of Genova;
Max Planck Institut für Kolloid- und Grenzflächenforschung Potsdam;
Friedrich-Alexander-Universiteit Erlangen;
Lulea Tekniska Universitet;
University of Brighton;
Friedrich-Shiller Universitat Jena;
University of Basel;
PreSens;
University of York;
Leeds University;
Weizmann Institute;
Leibniz-Institut für Neue Materialien GmbH

Projects

Publications & Patents

Menale, C., Campodoni, E., Palagano, E., Mantero, S., Erreni, M., Inforzato, A., … & Tampieri, A. (2019). Mesenchymal Stromal Cell‐Seeded biomimetic scaffolds as a factory of soluble RANKL in Rankl‐deficient osteopetrosis. Stem cells translational medicine, 8(1), 22-34.
Dellaquila, A., Greco, G., Campodoni, E., Mazzocchi, M., Mazzolai, B., Tampieri, A., … & Sandri, M. (2019). Optimized production of a high‐performance hybrid biomaterial: biomineralized spider silk for bone tissue engineering. Journal of Applied Polymer Science.
Polymeric 3D scaffolds for tissue regeneration: Evaluation of biopolymer nanocomposite reinforced with cellulose nanofibrils
Krishnakumar, G. S., Gostynska, N., Dapporto, M., Campodoni, E., Montesi, M., Panseri, S., … & Sandri, M. (2018). Evaluation of different crosslinking agents on hybrid biomimetic collagen-hydroxyapatite composites for regenerative medicine. International journal of biological macromolecules, 106, 739-748.
Krishnakumar, G. S., Gostynska, N., Campodoni, E., Dapporto, M., Montesi, M., Panseri, S., … & Sandri, M. (2017). Ribose mediated crosslinking of collagen-hydroxyapatite hybrid scaffolds for bone tissue regeneration using biomimetic strategies. Materials Science and Engineering: C, 77, 594-605.
Scaglione S., Giannoni P., Bianchini P., Sandri M., Marotta R., Firpo G., Valbusa U., Tampieri A., Diaspro A., Bianco P. and Quarto R. Order versus Disorder: in vivo bone formation within osteoconductive scaffolds. In: Scientific Reports (Nature) Publ. Febr. 2012 2 : 274 | DOI: 10.1038/srep00274
Tampieri A., Sprio S., Sandri M. et al. Mimicking natural bio-mineralization processes: A new tool for osteochondral scaf-fold development. Trends in Biotechnology 29(2011) 526-35.
Babiker H., Ding M., Sandri M., Tampieri A., Overgaard S. The effects of bone marrow aspirate, bone graft and collagen composites on fixation of titanium implants. In: Journal of Biomedical Materials Research: Part B – Applied Biomaterials (2011) – DOI: 10.1002/jbm.b.32509
Tampieri A., Landi E., Valentini F., Sandri M., D’Alessandro T., Dediu V. and Marcacci M. A conceptually new type of bio-hybrid scaffold for bone regeneration. In: Nanotechnology. 22; (2011) 105-104.
A. Tampieri, M. Sandri, et al. Design of graded biomimetic osteochondral composite scaffolds Biomaterials 29 (26), (2008) 3539-46.
Brevetto Internazionale (PCT/IB2006/000452) WO2006092718 Cartilaginiform and osteochondral substitute comprising multilayer structure and use thereof. Tampieri A., Pressato D., De Luca C., Di Fede S., Landi E.
Brevetto Internazionale (PCT/IB2006/002843) WO 2007/045953: A composite based on an apatite and a polysaccharide, method for its preparation and uses thereof. Landi E., Tampieri A., Sandri M., Di Fede S., Pressato D.