Mimicking bone extracellular matrix: Integrin-binding peptidomimetics enhance osteoblast-like cells adhesion, proliferation, and differentiation on titanium

Abstract

Interaction between the surface of implants and biological tissues is a key aspect of biomaterials research. Apart from fulfilling the non-toxicity and structural requirements, synthetic materials are asked to direct cell response, offering engineered cues that provide specific instructions to cells. This work explores the functionalization of titanium with integrin-binding peptidomimetics as a novel and powerful strategy to improve the adhesion, proliferation and differentiation of osteoblast-like cells to implant materials. Such biomimetic strategy aims at targeting integrins αvβ3 and α5β1, which are highly expressed on osteoblasts and are essential for many fundamental functions in bone tissue development. The successful grafting of the bioactive molecules on titanium is proven by contact angle measurements, X-ray photoelectron spectroscopy and fluorescent labeling. Early attachment and spreading of cells are statistically enhanced by both peptidomimetics compared to unmodified titanium, reaching values of cell adhesion comparable to those obtained with full-length extracellular matrix proteins. Moreover, an increase in alkaline phosphatase activity, and statistically higher cell proliferation and mineralization are observed on surfaces coated with the peptidomimetics. This study shows an unprecedented biological activity for low-molecular-weight ligands on titanium, and gives striking evidence of the potential of these molecules to foster bone regeneration on implant materials.

Selective binding and lateral clustering ofα5β1 andαvβ3 integrins: Unraveling the spatial requirements for cell spreading and focal adhesion assembly

“…However, this critical nanoscale spacing between cyclic RGD peptides left unclear the question whether the α5β1 and/or αvβ3 integrins that recognize these ligands, would cooperate and contribute in a manner similar to the formation of focal adhesions upon modulation of integrin clustering. Toward this aim, α5β1 and αvβ3 integrin selective peptidomimetics have been developed and linked to gold and titanium substrates to test the specific adhesion of α5β1 or αvβ3-expressing fibroblasts to the prepared surfaces 18,28 . The use of such selective ligands for cell adhesion studies is a powerful means to determine the different functions of these integrin types, without perturbing the expression of the cell receptors themselves 3 …”

Development of a versatile procedure for the biofunctionalization of Ti-6Al-4V implants

“…Aminosilanes are used as precursors in this procedure because they are able to bond with hydroxyl groups which may be induced on the oxidized surface of metals [14,15] and, in particular, may be used to functionalize titanium and its alloys [16][17][18][19]. In turn, the resulting amino groups of the functionalized surface are capable of binding themselves to a wide range of biomolecules [20].…”

“…The difficulties associated with IS are firstly related with the need for surface activation to induce the appearance of -OH groups at the surface. Activation requires a pre-processing of the material by either immersion in acid [19,24] or with an oxygen plasma treatment [16]. Secondly, IS tends to result in a relatively low concentration of amine functional groups on the surface which, in addition, may be non-homogeneously distributed.…”

Surface properties and early murine pre-osteoblastic cell responses of phosphoric acid modified titanium surface

“…Though, the number of attached cells was similar at 1 h. There are several studies demonstrating the correlation of cell attachment and osteogenic differentiation ability. 30,31 Thus, the significant increase of cell attachment on H 3 PO 4 treated titanium surface at early time point may contribute to later cell differentiation, though, the evidence was not strong to conclude this hypothesis. More investigations are indeed necessitated.…”