title: 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 h, 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.
authors.affiliation: Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Raphel
authors.affiliation: Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Karlsson
authors.affiliation: Department of Prosthodontics, Faculty of Odontology, Malmö University, Malmö, Sweden.
authors.forename: Silvia
authors.initials: S
authors.lastname: Galli
authors.affiliation: Department of Prosthodontics, Faculty of Odontology, Malmö University, Malmö, Sweden.
authors.forename: Ann
authors.initials: A
authors.lastname: Wennerberg
authors.affiliation: Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lindsay
authors.affiliation: Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Haugh
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
authors.forename: Jukka
authors.initials: J
authors.lastname: Pajarinen
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
authors.affiliation: Department of Prosthodontics, Faculty of Odontology, Malmö University, Malmö, Sweden; Department of Oral and Maxillofacial Surgery and Oral Medicine, Faculty of Odontology, Malmö University, Malmö, Sweden.
authors.forename: Ryo
authors.initials: R
authors.lastname: Jimbo
authors.affiliation: Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Andersson
authors.affiliation: Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA. Electronic address: heilshorn@stanford.edu.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Heilshorn
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001842:Bone and Bones / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D015921:Dental Implants; D004549:Elastin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D009985:Orthopedics; D016348:Osseointegration / Q000187:drug effects*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D010012:Osteogenesis / Q000187:drug effects; D019919:Prosthesis Implantation; D015202:Protein Engineering; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D014025:Titanium / Q000494:pharmacology
chemical_list: D020099:Coated Materials, Biocompatible; D015921:Dental Implants; D004549:Elastin; D014025:Titanium
keywords: Biomedical applications; Engineered proteins; Functional coatings; Hydrogels; Tissue engineering