Engineered protein coatings to improve the osseointegration of dental and orthopaedic implants

Abstract

Here we present the design of an engineered, elastin-like protein (ELP) that is chemically modified to enable stable coatings on the surfaces of titanium-based dental and orthopaedic implants by novel photocrosslinking and solution processing steps. The ELP includes an extended RGD sequence to confer bio-signaling and an elastin-like sequence for mechanical stability. ELP thin films were fabricated on cp-Ti and Ti6Al4V surfaces using scalable spin and dip coating processes with photoactive covalent crosslinking through a carbene insertion mechanism. The coatings withstood procedures mimicking dental screw and hip replacement stem implantations, a key metric for clinical translation. They promoted rapid adhesion of MG63 osteoblast-like cells, with over 80% adhesion after 24 hours, compared to 38% adhesion on uncoated Ti6Al4V. MG63 cells produced significantly more mineralization on ELP coatings compared to uncoated Ti6Al4V. Human bone marrow mesenchymal stem cells (hMSCs) had an earlier increase in alkaline phosphatase activity, indicating more rapid osteogenic differentiation and mineral deposition on adhesive ELP coatings. Rat tibia and femur in vivo studies demonstrated that cell-adhesive ELP-coated implants increased bone-implant contact area and interfacial strength after one week. These results suggest that ELP coatings withstand surgical implantation and promote rapid osseointegration, enabling earlier implant loading and potentially preventing micromotion that leads to aseptic loosening and premature implant failure.

Treatments for enhancing the biocompatibility of titanium implants

“…Organic coatings include particularly coatings based on ECM proteins, e.g. collagen 57 , fibronectin 58 , vitronectin 59 , elastin-like proteins 60 and peptides, such as RGD-or KRSR-containing adhesion oligopeptides 61 , and antimicrobial LL-37 peptides, which also stimulated the migration and osteogenic differentiation of bone marrow mesenchymal stem cells 62 . However, these coatings, although promising, still remain at the experimental level.…”

Tackling the Concept of Symbiotic Implantable Medical Devices with Nanobiotechnologies

“…As an example, a dental prosthesis made in titanium or zirconia ceramic is designed to be long with a rough surface, and has to be implanted without the presence of other tissues than the bone, like granulation or connective tissues. The main research direction concerning metallic or ceramic prosthesis focuses on coatings capable to improve the osteointegration and on deterioration of contact surfaces of total articulation prosthesis by friction …”

Integrating concepts of material mechanics, ligand chemistry, dimensionality and degradation to control differentiation of mesenchymal stem cells

“…Nevertheless, in cases where the tethered adhesive ligand or protein is more compliant than the substrate to which it is anchored, it is possible that the tethering itself is an important factor in mediating MSC differentiation (31). Such cases exist in orthopaedic and dental biomaterials applications where protein coatings are frequently tethered to metallic substrates (32, 33). Further research on this aspect of cellular mechanotransduction is required to complete our understanding of cellular response to substrate mechanics (31).…”