| 4.1 Final publishable summary report
Executive Summary
The goal ofVascuBone was to develop a “tool box“ composed of combinable parts to optimize bone
regeneration taking into account the respeetive patient‘s situation. At the end of Vascußone the “tool
box“ ineludes modified Censorb®M (#-TCP) materials and new developed composite materials for
die reconstmction ofnot critical and critical size defects. The major improvement of this new bone
implant materials is die newly developed and standardized modification with different diamond
particles (DP) ranging from nano- to microciyslalline sizes improving the hydrophilicity ofthe
materials due to high surface wettabihty ofthe diamond itseif and promoting cellular proliferation,
differentiation, and bone formation in small (mice, rats) as weil as in large (sheep) animal models.
New methods to surface-modil‘>‘ the nDPs by polylactide and benzoquinone have been established:
composite scaffold of poly(LLA-co-CL)/polylactide modified nanodiamond
(n-DP-PLMpoly(LLA-co-CL)), and poly(LLA-co-CL)/benzoquinone modifled nanodiamond
(n-DP-BQfpoly(LLA-co-CL)).
The company Diacoating GmbH, Innsbruck Austria was founded by Vascußone members and die
produetion processes were established and tested for reproducibiiity. Process documentation due to
180-standards was developed and is available. DiaCoating will bring the new material as weIl as the
new modification technology on the market and ensures the sustainability of materials developed in
VascuBone. The new materials were tested according to DIN ISO 10993-12: 2009 and found tobe
non cytotoxic and biocompatible. Furthermore, an intravenous dose toxicity study ofthe nano
diamond particles prove that the nDP appeared to be safe. Beside the material development one
major focus ofVascußone was to develop new tools to control and ensure safety, immunological
aceeptance and efflcacy ofnew implants including nano-materials and ATMPS. A highlight to this
respect is die development oforganotypic tissue modeis ta proof tumorigenicity of new materials.
Additionaily, a successful design has been established to investigate in vivo environmentaily-induced
carcinogenesis and 10 monitor implanted materials/scaffolds by bioluminescence in an anempt to
surpass die limitations ofthe long term rodent assays. Last but not least all these new models were
used for in vitro — in vivo correlation studies to validate the new models.
Otter important components of die Vaseußone “mol box“ are based on in vivo imaging of the bone
implant to visualize existing vessels and the formation of neovessels in the healing bone. Multiple
optimized angiography contrast agents for in vivo MRI investigation ofblood flow were developed
in the consortium and are included in the VascuBone “tool box“. fle imaging agents were vadous
and included gadolinium-based agents and iron oxide-based agents, for positive contrast and negative |