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Peptide-coating for metals in particular titanium e.g. to improve osseointegration of implants

Country of Origin: Germany
Reference Number: TODE20190305001
Publication Date: 13 March 2019

Summary

A German university has succeeded in modifying a molecule in a way to effectively promote the osseointegration of implants. It is known that a posttranslational modified amino acid L-3,4-dihydroxyphenylalanine (DOPA), found in proteins secreted by the blue mussel (Mytilus edulis), can bind to the oxidized surface of titanium without previous chemical treatment. The university is looking for partners from industry for further technical research (Joint Venture) and for license agreements.

Description

Titanium (Ti) is the material of choice for orthopedic and dental implants. During the osseous healing process, the osteoblasts grow directly onto the implant resulting in a firm adhesion to the implant surface. However, poor osseointegration can result in inflammation, loosening or subsidence of the implant. Attempts have been made to reinforce the osseointegration by using components of the extracellular matrix to improve the biocompatibility of the titanium surface. Such peptide coatings play an important role in the imitation of cell adhesive properties. 
But up to now functionalization of the surface is often necessary to achieve a direct immobilization of these molecules.
The peptide L-3,4-dihydroxyphenylalanine (DOPA) can bind to the oxidized surface of titanium without previous chemical treatment in a wet environment. This posttranslational modified peptide has been found in proteins secreted by the blue mussel (Mytilus edulis).
As a novel concept, the very stable and affine titanium surface adhesive properties were combined with specific cell binding moieties in one molecule by a German university.
The Cyclic Arg-Gly-Asp (RGD) pentapeptides have a high affinity and specificity towards certain integrins and can mediate strong cell adhesion. Furthermore, the peptide sequence FHRRIKA, derived from the bone sialoprotein, is suggested to bind to heparin sulfate containing proteoglycans and thus promote cell attachment.
Since integrin-mediated cell adhesion is described to be supported by proteoglycan interactions, we suggest that a combination of c[RGDfK] and FHRRIKA adjacent to each other and within one molecule is desired tostimulate cell-surface interactions.
The combination of a main chain with a DOPA, an integrin-binding and a heparin-binding peptide shows synergetic effect on the cell adhesion to metallic surfaces that have been coated with this specific peptide.
Conjugating the cyclic RGD and HBP in one peptide gave improved spreading, proliferation, viability, and the formation of well-developed actin cytoskeleton and focal contacts of osteoblast-like cells.
The department for biotechnology and biomedicine of a German university is looking for partners from industry who will possibly contribute to the further development in order to design a product under Joint Venture cooperation and to start the market launch under license agreement.

Advantages and Innovations

The technology offers the following advantages:
• Effective, modified molecule for the improvement of the osseointegration of implants
• Excellent binding of the proteins to metal surfaces, in particular titanium
• Very good peptide stability in aqueous solution
• no functionalization of the surface necessary
• Coating may be enhanced with other substances

Stage Of Development

Under development/lab tested

Stage Of Development Comment

The method has been experimentally verified by
cell adhesion tests.

Requested partner

Collaboration partners from industry are sought who will possibly contribute to the further development in order to create a product under a Jonit Venture cooperation.

Furthermore partners from industry are sought with interest in taking over the technology/ product for market launch under license agreement.

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