Resorbable multimodal hybrid materials for regenerative medicine especially for reconstructive jaw and facial surgery

• Applicants: Professor Dr. Herbert Jennissen; Professor Charles James Kirkpatrick, Ph.D.; Professor Dr. Goerg H. Michler
• Subject Area: Dentistry, Oral Surgery
• Term: from 2004 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5439263

The immobilization of growth factors on biomaterials for the stimulation of bone growth was published by us in 1999 for the first time. Why are such implants not on the market today? The surprising answer is: Because human BMP-2 is much more effective in animals than in man. Stated differently, BMP-2 has to be applied in 100-1000fold higher (i.e. unphysiological) doses in humans with strong side effects e.g. in the spine. In the present DFG-application it is proposed to achieve a dose reduction by following the example of bone healing, in which a variety of growth factors is released in a consecutive spatio-temporal order. Therefore the main objective of this DFG-project continues to be the gaining of new insights into the engineering of multimodal, bioactive hybrid nanofiber scaffolds for enhancing bone healing in the craniofacial area of humans.It is proposd to employ the versatile method of Electrospinning resorbable polymers such as polylactide to hybrid scaffolds to which growth factors are either added to the interior of the fiber by encapsulation or to the surface by adsorption. As demonstrated in the DFG-Research report (Anlage 01) the four intermediate objectives of the past application period were fully achieved. Results which might be listed as outstanding are: (i) visualization of single protein molecules by SEM and an identified polydisperse size distribution of the proteins (inclusates) within single nanofibers; (ii) identification of the release mechanism as a zero-order reaction; (iii) Release of encapsulated VEGF after 96 days in unchanged highest biological activity; (iv) Fabrication of nanofiberscaffolds with bimodal release properties from adsorbates of VEGF and BMP-2 in form of first-order reactions; (v) Formation of capillary-like vessel structures with an open lumen on VEGF releasing nanofiber scaffold in dual cell coculture.In the following proposal the physical-chemical properties of the nanofiber scaffolds (hydrolysis time, shrinkage, nanoporosity) and those of the protein-inclusates (dispersity) must be improved. This should allow the development of a spatio-temporal release of various growth factors which are to be tested in animals (rat). These experiments should lay the foundation for the specific development of a biohybrid nanofiber barrier membrane for guided bone regeneration (GBR/GTR) in the cranio-facial region.The success of these very demanding aims will last-not-least be a result of the excellent colleagueship and open- mindedness of the three well-tried working groups, together with PD Dr. S. Ghanaati, the welcome newcomer in Frankfurt.

• DFG Programme: Research Grants
• Co-Investigator: Privatdozent Shahram Michael Ghanaati, Ph.D.