The OPHIS project

Osteoarthritis (OA) and osteoporosis (OP) are disabling, degenerative bone diseases with significant economic and societal impacts. The incidence of these conditions increases with age but in recent years the number of younger patients has increased, due mainly to factors related to modern life-styles.

The efficiency of current pharmacologic and implant-based solutions are limited and often poorly tolerated. OPHIS aimed to develop new, engineered biomaterials for the regeneration of both the osteo-chondral region and the vertebral body degenerated by OA and OP. These devices were based on the unique combination of biological triggers in the form of (i) nanostructured biomaterials able to mimic the extracellular matrices of either bone or cartilage (ii) chemical and biochemical cues able to direct, control and preserve the phenotypes of the relevant cells in their respective histological compartments.

OPHIS explored the frontiers of knowledge of the effect of nano-structures on tissue regeneration and lead to the de-novo design of active structures able to trigger this process. User friendly and highly performing tissue substitutes were developed as both acellular and cellular matrices for the regeneration of specific anatomical regions compromised by OA and OP. Focus was also given to the study of the interactions occurring at nano-scale level between the implanted materials and the natural tissues. This information complements the body of data obtained through clinically reflective in vitro and in vivo models. Dissemination was integrated step-wise with the strategy for intellectual property protection and exploitation.

Project timeframe

The project ran from September 2010 to August 2014.

Project aims

OPHIS aimed to develop new engineered biomaterials for the repair and regeneration of both osteochondral regions and vertebral bodies in patients affected by severe osteoarthritis and osteoporosis.

Project findings and impact

All the milestones foreseen in OPHIS were reached in time. The main results and achievements of the project OPHIS are summarised as follows:

  • New bio-polymeric matrices and blends suitable for guided assembling/mineralisation and generation of 3D scaffolds for bone and osteochondral regeneration with designed composition and microstructure.
  • New hybrid bone and osteochondral scaffolds presenting dendrimer-mediated functionalisation triggering bone and vascular regeneration.
  • Apatite nano-phases with multiple bio-competent ion-substitution.
  • New αTCP phases presenting tailored substitution with strontium.
  • New injectable, self-setting pastes based on Sr-αTCP with tailored viscosity, setting time and mechanical strength.
  • New injectable self-setting cements based on Sr-substituted apatites with enhanced osteogenic and osteoconductive ability.
  • New alginate-based osteochondral scaffolds.
  • New bone scaffolds based on bacterial nanocellulose.
  • New semi-dendrimers exposing O2 scavengers as triggers of chondrocytic differentiation.
  • New semi-dendrimers mediating gene transfection.
  • New peptide sequences mimicking bone (BMP-2), cartilage (IGF-1) and vascular (VEGF) growth factors.
  • New polymeric nanobeads with controlled size and ability of controlled delivery.
  • New pH-sensitive bio-polymeric constructs with ability of controlled delivery.
  • Preliminary assessment of a AFM nanoindentation-based method to predict, in a quantitatively and spatially resolved way, the behaviour of grafts for osteochondral regeneration upon implantation.

Following in vitro testing to verify their cellular compatibility, the biomaterials developed by the OPHIS consortium hold great exploitation potential and could prove beneficial for sufferers of degenerative bone disorders.

Research team

Professor Matteo Santin

Dr Steve Meikle

Dr Anna Guildford

Dr Mariagemiliana Dessi

Dr Valeria Perugini

Dr Mark Best

Output

Osteochondral scaffold reconstruction for complex knee lesions: a comparative evaluation
Filardo, G.; Kon, E; Perdisa, F.; Di Matteo, B.; Di Martino, A.; Iacono, F.; Zaffagnini, S.; Balboni, F.; Vaccari, V.; Marcacci, M.
The Knee 2013
doi:10.1016/j.knee.2013.05.007

Spinal Fusion in the Next Generation: Gene and Cell Therapy Approaches
Marta Barba; Claudia Cicione; Camilla Bernardini; Vincenzo Campana; Ernesto Pagano; Fabrizio Michetti; Giandomenico Logroscino; Wanda Lattanzi
Hindawi Publishing Corporation The Scientific World Journal, Vol 2014 (2014) 2014
pmc:PMC3927763, doi:10.1155/2014/406159

Lim Mineralization Protein 3 Induces the Osteogenic Differentiation of Human Amniotic Fluid Stromal Cells through Kruppel-Like Factor-4 Downregulation and Further Bone-Specific Gene Expression
Marta Barba; Filomena Pirozzi; Nathalie Saulnier; Tiziana Vitali; Maria Teresa Natale; Giandomenico Logroscino; Robbins, Paul D.; Andrea Gambotto; Giovanni Neri; Fabrizio Michetti; Enrico Pola; Wanda Lattanzi
Hindawi Publishing Corporation BioMed Research International, Vol 2012 (2012) 2012
doi:10.1155/2012/813894, pmc:PMC3471036

Expansion of human mesenchymal stromal cells from fresh bone marrow in a 3D scaffold-based system under direct perfusion.
Adam Papadimitropoulos; Elia Piccinini; Sophie Brachat; Alessandra Braccini; David Wendt; Andrea Barbero; Carsten Jacobi; Ivan Martin
Public Library of Science (PLoS) PLoS ONE, Vol 9, Iss 7, p e102359 (2014)
doi:10.1371/journal.pone.0102359, pmc:PMC4096512

In-Depth Oral Presentations, Oral Communications and Round Table
Springer Milan Journal of Orthopaedics and Traumatology 2011
pmc:PMC4417749, doi:10.1007/s10195-011-0151-1

Novel Nano-composite Multilayered Biomaterial for Osteochondral Regeneration: A Pilot Clinical Trial
Kon, E; Delcogliano, M.; Filardo, G.; Busacca, M.; Di Martino, A.; Marcacci, M.
The American Journal of Sports Medicine 2011
doi:10.1177/0363546510392711

Clinical results of multilayered biomaterials for osteochondral regeneration
Kon, Elizaveta; Filardo, Giuseppe; Perdisa, Francesco; Venieri, Giulia; Marcacci, Maurilio
Springer Berlin Heidelberg Journal of Experimental Orthopaedics 2014
pmc:PMC4648845, doi:10.1186/s40634-014-0010-0

Treatment of Knee Osteochondritis Dissecans With a Cell-Free Biomimetic Osteochondral Scaffold: Clinical and Imaging Evaluation at 2-Year Follow-up
Filardo, G.; Kon, E; Di Martino, A.; Busacca, M.; Altadonna, G.; Marcacci, M.
The American Journal of Sports Medicine 2013
doi:10.1177/0363546513490658

Cell-laden biphasic scaffolds with anisotropic structure for the regeneration of osteochondral tissue
Schütz, Kathleen; Despang, Florian; Lode, Anja; Gelinsky, Michael
Journal of Tissue Engineering and Regenerative Medicine 2014
doi:10.1002/term.1879

Unveiling the intracellular trafficking of drug-loaded dendrimer nanoparticles in astrocytes
Cerqueira, Susana R.; Chowdhury, Helena H.; Mano, J. F.; Oliveira, Joaquim M.; Sousa, Nuno; Zorec, Ribert; Reis, R. L.
John Wiley & Sons, Ltd. 2014
doi:10.1002/term.1931,

Hybrid Scaffolds for Tissue Regeneration: Chemotaxis and Physical Confinement as Sources of Biomimesis
Simone Sprio; Monica Sandri; Silvia Panseri; Carla Cunha; Anna Tampieri
Hindawi Publishing Corporation Journal of Nanomaterials, Vol 2012 (2012) 2012
doi:10.1155/2012/418281

Scaffold-Based Repair for Cartilage Healing: A Systematic Review and Technical Note
Filardo, Giuseppe; Kon, Elizaveta; Roffi, Alice; Di Martino, Alessandro; Marcacci, Maurilio
Arthroscopy: The Journal of Arthroscopic & Related Surgery 2013
doi:10.1016/j.arthro.2012.05.891

Cellulose scaffolds with an aligned and open porosity fabricated via ice-templating
Flauder, Stefan; Heinze, Thomas; Müller, Frank A.
Springer Cellulose 2013
doi:10.1007/s10570-013-0119-9

Bone substitutes in orthopaedic surgery: from basic science to clinical practice
Campana, V.; Milano, G.; Pagano, E.; Barba, M.; Cicione, C.; Salonna, G.; Lattanzi, W.; Logroscino, G
Springer US Journal of Materials Science. Materials in Medicine 2014
pmc:PMC4169585, doi:10.1007/s10856-014-5240-2

Structure and mechanical properties of β-TCP scaffolds prepared by ice-templating with preset ice front velocities
Flauder, Stefan; Gbureck, Uwe; Müller, Frank A.
Acta Biomaterialia 2014
doi:10.1016/j.actbio.2014.08.020

Interleukin-1 beta mosulates endochondral ossification by human adult bone marrow stromal cells
Mumme, Marcus; Scotti, Celeste; Papadimitropoulos, Adam; Todorov, Athanas; Hoffmann, Waldemar; Bocelli-Tyndall, Chiara; Jakob, Marcel; Wendt, David; Martin, Ivan; Barbero, Andrea
AO Research Institute Davos ARI 2012

Mimicking natural bio-mineralization processes: A new tool for osteochondral scaffold development
Tampieri, Anna; Sprio, Simone; Sandri, Monica; Valentini, Federica
Elsevier Science London Trends in Biotechnology 2011
doi:10.1016/j.tibtech.2011.04.011

Biomimetic magnesium–carbonate-apatite nanocrystals endowed with strontium ions as anti-osteoporotic trigger
Iafisco, Michele; Ruffini, Andrea; Adamiano, Alessio; Sprio, Simone; Tampieri, Anna
Elsevier Science BV Materials Science and Engineering: C 2014
doi:10.1016/j.msec.2013.11.009

Partners

Consiglio Nazionale Delle Ricerche – Italy (Coordinator)

Friedrich-Schiller-Universiy of Jena – Germany

University Hospital Basel – Switzerland

Fin-Ceramica Faenza Spa – Italy

Dresden Technical University – Germany

Istituto Ortopedico Rizzoli – Italy

Laboratoire D'evalution Des Materiels Implantables Sa – France

Universita Cattolica Del Sacro Cuore - Italy