Reversibly tethering growth factors to surfaces: guiding cell function at the cell-material interface

Abstract

Development of novel methodologies for tethering growth factors (GFs) to materials is highly desired for the generation of biomaterials with improved tissue repair properties. Progress in the development of biomaterials that incorporate GFs and the in vivo performance of such biomaterials in tissue engineering applications, such as stents, orthopaedic implants, sutures and contact lenses, is still challenged by the required control over the mobility of growth factors in biomaterials. Many of the current methodologies to introduce GFs in biomaterials suffer from a lack of control over the spatiotemporal delivery of GFs. The aim of the work described in this thesis is the functional tethering of GFs to biomaterials using reversible chemical strategies with spatiotemporal control, thus following nature’s paradigm. This work consisted of three parts: a) non-covalent strategies have been used to capture GFs to surfaces by employing nanobodies and peptides. In this part of the research considerable attention has been paid as well to fundamental aspects on controlling protein orientation in densely packed layers; b) reversible covalent chemistry has been used to control the spatiotemporal availability of GFs in the extracellular matrix (ECM) by using hydrolysable siloxane and imine bonds as examples and c) a protein array technology has been introduced to create functional platforms of various shapes and content for studying cell behavior. In summary, the reversibility of the tether has been found to play important roles in the biological activity. The results of the studies demonstrate the advantage of tethers that combine immobilized GFs, such as GF stability or the creation of locally highly concentrated GF reservoirs, with released mobile GFs, such as optimization of orientation for an optimal interaction with cellular receptors. Although such systems are attractive, knowledge about the application of such tethering strategies in vivo is limited and deserves detailed attention in future research and leaves ample room for synthesis. For example, stimuli responsive systems might provide tools for a breakthrough in the tissue engineering field.