Material-based strategies seek to engineer synthetic microenvironments that mimic the characteristics of physiological extracellular matrices for applications in regenerative therapies, including bone repair and regeneration. In our group, we identified a specific chemistry, poly(ethyl acrylate) (PEA), able to induce the organization of fibronectin (FN), upon adsorption of the protein, into fibrillar networks similar to the physiological ones, leading to enhanced cellular response, in terms of cell adhesion and differentiation. In this work, we exploit these FN networks to capture and present growth factors (GF) in combination with the integrin binding domain of FN during bone tissue healing. Fibrillar conformation of FN adsorbed on PEA favors the simultaneous availability of the GF binding domain (FNIII12–14) next to the integrin binding region (FNIII9–10), compared to poly(methyl acrylate) (PMA), a material with similar chemistry, where FN adopts a globular conformation. The combined exposure of specific adhesive sequences recognized by integrins and GF binding domains was found to improve the osteogenic differentiation of mesenchymal stem cells. A higher expression of bone proteins was found when BMP2 is bound or sequestered on the material surface versus its administration in the culture media in vitro. The potential of this system as recruiter of GFs was also investigated in a critical-size bone segmental defect in mouse. The synergistic integrin-GF signalling, induced by fibrillar FN, promoted bone formation in vivo with lower BMP2 doses than current technologies. Furthermore, we optimized the system for its potential use in translational research, seeking to address the clinical need of using biocompatible and biodegradable material implants. Polycaprolactone scaffolds were synthesized and coated with a thin layer of plasma- polymerized PEA that recruits and efficiently presents GF during healing of critical size defects. The material-driven FN fibrillogenesis provides a new strategy to efficiently reduce the GF doses administrated in bone regenerative therapies.
Polyether ether ketone (PEEK) has been increasingly employed as biomaterials for trauma, orthopeadic, and spinal implants. However, concern has been raised about the inertness of PEEK which limits bone integration. In this study, we have coated PEEK with a functional material seeking to promote osteogenic differentiation of human mesenchymal stem cells (hMSC). We have used spray drying to coat poly(ethyl acrylate) (PEA) as a coating on PEEK. This technique is simple, allows a range of controlled coating thicknesses (from hundred nm to a few um), cost effective and easily translatable to scaffolds or implant surfaces for existing or new orthopaedic applications. PEA induces the organisation of fibronectin (FN) into nanonetworks upon simple adsorption from protein solutions. These FN nanonetworks on PEA represent a microenvironment for efficient growth factor binding and presentation in very low but effective doses. In this study we show cell adhesion and stem cell differentiation towards an osteogenic lineages when bone morphogenetic protein 2 (BMP2) was adsorbed on these engineered PEEK/PEA/FN microenvironments in very low doses. Overall, the developed functional coatings on PEEK has the potential to allow the translation of this material into orthopaedic applications.
