A molecular toolkit for the functionalization of titanium-based biomaterials that selectively control integrin-mediated cell adhesion

Abstract

We present a click chemistry- based molecular toolkit for the bio- functionalization of materials to selec- tively control integrin-mediated cell ad- hesion. To this end, a 5 b 1-selective RGD peptidomimetics were covalently immobilized on Ti-based materials, and the capacity to promote the selective binding of a 5 b 1 was evaluated using a solid-phase integrin binding assay. This functionalization strategy yielded surfa- ces with a nine-fold increased affinity for a 5 b 1, in comparison to control samples, and total selectivity against the binding of the closely related integ- rin a v b 3. Moreover, our methodology allowed the screening of several phos- phonic acid containing anchoring units to find the best spacer–anchor moiety required for establishing an efficient binding to titanium and to promote se- lective integrin binding. The integrin subtype specificity of these biofunc- tionalized surfaces was further exam- ined in vitro by inducing selective ad- hesion of genetically modified fibro- blasts, which express exclusively the a 5 b 1 integrin. The versatility of our molecular toolkit was proven by shift- ing the cellular specificity of the mate- rials from a 5 b 1- to a v b 3-expressing fi- broblasts by using an a v b 3-selective peptidomimetic as coating molecule. The results shown here represent the first functionalization of Ti-based mate- rials with a 5 b 1- or a v b 3-selective pep- tidomimetics that allow an unprece- dented control to discriminate between a 5 b 1- and a v b 3-mediated adhesions. The role of these two integrins in dif- ferent 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 ad- hesion and the development of new bi- omaterials targeting specific cell types