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3. Bioactive and functionalised implants for the regeneration of hard connective tissues

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The activity is dedicated to the development of porous implants with hierarchically organized structure, to mimic the morphological-structural characteristics of bone and to exhibit adequate biomechanical properties.
The so-obtained scaffolds exhibit high multi-modal open and interconnected porosity that favour cell habitation and proliferation (osteoconductivity), thus promoting the integration of the scaffold with surrounding tissues and the formation of a vascularisation network (angiogenesis), that is a key factor for a proper tissue regeneration. Besides angiogenic processes can be improved with specific vascular grow factors released from bioactive magnetic scaffold made of intrinsically magnetic hydroxyapatite and biocompatible magnetic phases.
Moreover the implants can show oriented porosity and anisotropic mechanical properties, similarly to what occurs in long bones.
Natural and bio-erodible polymers are used in blends with the ceramic phase to enhance fracture strength and tailor elastic properties towards those typical of bones. Moreover the polymeric phase can be cross-linked with biocompatible chemical agents in order to incorporate and release, with a controlled kinetic, bioactive molecules like drugs and grow factors.

Injectable cement pastes based on calcium phosphate blended with natural or bio-erodible polymers represent a new category of porous implant. They set in physiological conditions, transforming into biomimetic hydroxyapatite and act as porous bone cement with high regenerative properties for support of damaged spinal regions.

Recently porous structures have been developed through the application of morphosynthetic transformation processes by which it is possible to obtain devices with hierarchically organized structure. In particular some woods (e.g.: Rattan and Red Oak) have a morphology very similar to that of cortical and spongy bone, so they are subjected to multi-step process of chemical transformation that transforms cellulose into biomimetic hydroxyapatite without altering the original structure-morphology.
This class of devices is particularly addressed towards regeneration of long load-bearing bones, for which acceptable clinical solutions still do not exist.

PROCESSES AND FACILITIES

Porous implants are obtained from bioactive and bio-reabsorbable ceramic powders via different forming techniques:
- replica
- foaming
- spin casting
- slip casting
- freeze casting
Such techniques are based on the processing of ceramic powders in stable aqueous suspensions with suitable viscosity that allow to obtain ceramic devices with high interconnected porosity and mechanical properties similar to spongy bone.

3.1 3.2

Bioactive cement are prepared through process of hydrolysis starting from biomimetic phases, calcium phosphate based, containing anti-osteoporotic agents such as Strontium ions. The pastes (particles size 10 m) are consolidate at 37°C by using low amounts of setting accelerator.

3.3 3.4

Morpho-sintetic transformations of natural templates are developed through multi-step ceramization processes (gas-solid reaction, ionic substitution) in furnace or autoclave.
These processes occur on molecular scale with controlled kinetic and reproducind the starting structures of plants.

3.5 3.6 3.7 3.8

PUBBLICATIONS AND PATENTS

- Sprio S., Ruffini A., Valentini F., D’Alessandro T., Sandri M., Panseri S., Tampieri A. Biomimesis and biomorphic transformations: New concepts applied to bone re generation. J. of Biotechnology 156 (4); (2011) 347-355.
- Sprio S., Ruffini A., Tampieri A. Smart biomaterials obtained by biomorphic transformation. In: Recent Advances in Nanostructured Materials: Synthesis, Characterization and Applications (AK Zachariah, N Kalarikkal, Y Weimin, AK Haghi eds.), Apple Academic Press Inc, Oakville, Canada (2011).
- Tampieri A., Sprio S. (2011) New concepts applied to the development of biomaterials for orthopaedic tissue regeneration. In: Surface tailoring of inorganic materials for biomedical applications (L. Rimondini ed.), Bentham Science Publisher.
- Sprio S, Tampieri A, Celotti G, Landi E. Development of Hydroxyapatite/calcium silicate composites addressed to the design of load-bearing bone scaffolds. J Mech Behav Biomed Mater 2 (2009) 147-155.
- Tampieri A, Sprio S, Ruffini A, Celotti G, Lesci IG, Roveri N. From Wood to Bone: multi-step process to convert wood hierarchical structures into biomimetic hydroxyapatite scaffolds for bone tissue engineering. J. Mater. Chem. 19 (28) (2009) 4973-4980.
- Landi E., Valentini F., Tampieri A. Porous hydroxyapatite/gelatine scaffolds with ice-designed channel-like porosity for biomedical applications. ACTA BiomaterialiA 4 (6) (2008) pp. 1620-1626.
- M. Sandri, A. Tampieri, E. Landi. New morphosynthetic processes for biomaterials development., J Appl Biomater Biomech 5 (3) (2007) 208.
- Tampieri A, Celotti G, Sprio S, Delcogliano A, Franzese S. Porosity-graded hydroxyapatite ceramics to simulate natural bone. Biomaterials 22 (2001) 1365-1370.

- International Patent MI2010A002070 (PCT/IB2011/054980): Implants for “load-bearing” bone substitutions having hierarchical organized architecture deriving from transformation of vegetal structures. Tampieri A., Sprio S., Ruffini A., Martínez-Fernández J., Torres Raya C., Varela Feria F.M., Ramírez Rico J., Harmand M.F.
- International Patent WO2008146113 (PCT/IB2008/001229) Process for coating a surface of a metal element to increase osteointegration there of and prosthetic device including said element. De Luca C., Di Fede S., Manara S., Marcaccio M., Paolucci F., Pressato D., Norberto R., Tampieri A.
- International Patent WO2007029276 (PCT/IT2006/000639) Pin for anchorage of articular prosthesis, articular prosthesis comprising said pin, tibial component and articular prosthesis for the knee comprising said tibial component. De Luca C., Di Fede S., Marcacci M., Pressato D., Tampieri A.
- Italian Patent ITBO20000038 (31/07/2001) Idrossiapatite a gradiente come materiale per sostituzioni ossee. Celotti G., De Santis E., Lorini G., Tampieri A.

MAIN SCIENTIFIC COLLABORATIONS
Laboratoire d’evaluation des materiels implantables (LEMI); FINCERAMICA Faenza S.p.A.; Istituti Ortopedici Rizzoli; Friedrich-Alexander-Universiteit Erlangen; University of Brighton; University of Basel; PreSens; Max Planck Institut für Kolloid- und Grenzflächenforschung Potsdam; University of Stockholm; Leibniz-Institut für Neue Materialien GmbH.

RELEVANT PROJECTS

TEMPLANT EU flag 6FP

TEM-PLANT, NMP4-CT-2006-033277 (2006-11), “New bio-ceramization processes applied to vegetable hierarchical structures”. Coord. Dr.ssa Anna Tampieri

OPHIS EU flag 7fp
OPHIS: “Composite Phenotypic Triggers For Bone and Cartilage Repair” (2010-2014). Coord. Dr.ssa Anna Tampieri