ausblenden:
Schlagwörter:
CYCLIC RGD PEPTIDES; FORMATION IN-VIVO; BONE-FORMATION; ALPHA-5-BETA-1
INTEGRIN; IMPLANT MATERIALS; TERMINAL ALKYNES; RATIONAL DESIGN;
SOLID-PHASE; SURFACES; LIGANDSbiomaterials; cell adhesion; click chemistry; integrins;
peptidomimetics; surface coating; titanium;
Zusammenfassung:
We present a click chemistry-based molecular toolkit for the biofunctionalization of materials to selectively control integrin-mediated cell adhesion. To this end, 51-selective RGD peptidomimetics were covalently immobilized on Ti-based materials, and the capacity to promote the selective binding of 51 was evaluated using a solid-phase integrin binding assay. This functionalization strategy yielded surfaces with a nine-fold increased affinity for 51, in comparison to control samples, and total selectivity against the binding of the closely related integrin v3. Moreover, our methodology allowed the screening of several phosphonic acid containing anchoring units to find the best spacer-anchor moiety required for establishing an efficient binding to titanium and to promote selective integrin binding. The integrin subtype specificity of these biofunctionalized surfaces was further examined in vitro by inducing selective adhesion of genetically modified fibroblasts, which express exclusively the 51 integrin. The versatility of our molecular toolkit was proven by shifting the cellular specificity of the materials from 51- to v3-expressing fibroblasts by using an v3-selective peptidomimetic as coating molecule. The results shown here represent the first functionalization of Ti-based materials with 51- or v3-selective peptidomimetics that allow an unprecedented control to discriminate between 51- and v3-mediated adhesions. The role of these two integrins in different biological events is still a matter of debate and is frequently discussed in literature. Thus, such bioactive titanium surfaces will be of great relevance for the study of integrin-mediated cell adhesion and the development of new biomaterials targeting specific cell types.
