Growth factor release systems for coating of implants
Surgical and orthopaedic implants manufactured from different materials are used for functional reconstruction of bones in human body. In view of structure and surface of the implants specific requirements are desired. The bone in-growth to implants by so-called osseointegration crucially depends on the surface of the implant. A modification of the surface can improve the anchoring of the implant into the bone and the compatibility of the implant and therefore accelerate its in-growth and shorten the healing process. Preferred materials for coating the implant surfaces are compounds which are able to stimulate bone formation. Growth factors based on proteins such as bone morphogenetic proteins (BMPs) are suited to induce a neoformation of bone. Especially BMP-2 in form of recombinant human BMP-2 (rhBMP; figure above: tertiary structure of the dimer; source: SwissProt) shows medical relevance, where BMP-2 bound to a support matrix serves as alternative for autologous bone graft.
To use the osteoinductive properties of rhBMP-2, the protein has to be available locally in a certain concentration range. The efficiency of BMP-2 has been proven by inducing the alkaline phosphatase activity in a murine osteoblastic cell line (MC3T3-E1; image sequence below).
Since rhBMP-2 shows a good water solubility no long-lasting effect will be achieved using pure rhBMP-2-coating. We developed a system for a retarded release of rhBMP-2 based on adducts of BMP-2 with ionic polymers. For those adducts natural biodegradable polysaccharide-based polymers were used which were modified with varying anionic and cationic functionalities. Thus they were forming sparingly water soluble rhBMP-2 precipitates which show good adhesion to implants. The cytocompatibility of the ionic polymers and the osteoinductive properties of rhBMP-2 released from these BMP-polymer adducts have been demonstrated in first in-vitro investigations.
Dr. Armin Kautz