title: A multifunctional streptococcal collagen-mimetic protein coating prevents bacterial adhesion and promotes osteoid formation on titanium.
abstract: The major barriers to the clinical success of orthopedic and dental implants are poor integration of fixtures with bone tissue and biomaterial-associated infections. Although multifunctional device coatings have long been considered a promising strategy, their development is hindered by difficulties in integrating biocompatibility, anti-infective activity and antithrombotic properties within a single grafting agent. In this study, we used cell adhesion assays and confocal microscopy of primary murine osteoblasts and human osteoblast cell lines MG-63 and Saos-2 to demonstrate that a streptococcal collagen-like protein engineered to display the α1 and α2 integrin recognition sequences enhances osteoblast adhesion and spreading on titanium fixtures. By measuring calcium deposition and alkaline phosphatase activity, we also showed that selective activation of α2β1 integrin induces osteoblast differentiation, osteoid formation and mineralization. Moreover, cell adhesion assays and scanning electron microscopy of clinical isolates Staphylococcus aureus Philips and Staphylococcus epidermidis 9491 indicated that streptococcal collagen-mimetic proteins inhibit bacterial colonization and biofilm formation irrespective of their interaction with integrins. Given that streptococcal collagenous substrates neither interact with platelets nor trigger a strong immune response, this novel bioactive coating appears to have desirable multifaceted properties with promising translational applications.
authors.affiliation: David H. Koch Center for Applied Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: Julianna K
authors.initials: JK
authors.lastname: Bronk
authors.affiliation: Center for Infectious & Inflammatory Diseases, Institute of Bioscience and Technology, Texas A&M Health Science Center, 2121 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: Brooke H
authors.initials: BH
authors.lastname: Russell
authors.affiliation: Center for Infectious & Inflammatory Diseases, Institute of Bioscience and Technology, Texas A&M Health Science Center, 2121 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Rivera
authors.affiliation: David H. Koch Center for Applied Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA; Department of Internal Medicine, University of New Mexico, 1201 Camino de Salud NE, Albuquerque, NM 87131, USA.
authors.forename: Renata
authors.initials: R
authors.lastname: Pasqualini
authors.affiliation: David H. Koch Center for Applied Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA; Department of Internal Medicine, University of New Mexico, 1201 Camino de Salud NE, Albuquerque, NM 87131, USA.
authors.forename: Wadih
authors.initials: W
authors.lastname: Arap
authors.affiliation: Center for Infectious & Inflammatory Diseases, Institute of Bioscience and Technology, Texas A&M Health Science Center, 2121 Holcombe Blvd., Houston, TX 77030, USA. Electronic address: mhook@ibt.tamhsc.edu.
authors.forename: Magnus
authors.initials: M
authors.lastname: Höök
authors.affiliation: David H. Koch Center for Applied Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA; Department of Infectious Diseases, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. Electronic address: mbarbu@SyntheticGenomics.com.
authors.forename: E Magda
authors.initials: EM
authors.lastname: Barbu
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D018441:Biofilms; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D003094:Collagen / Q000737:chemistry*; D051379:Mice; D008856:Microscopy, Fluorescence; D018716:Molecular Mimicry; D010006:Osteoblasts / Q000166:cytology*; D013210:Staphylococcus / Q000502:physiology*; D013291:Streptococcus / Q000737:chemistry*; D014025:Titanium
chemical_list: D020099:Coated Materials, Biocompatible; D003094:Collagen; D014025:Titanium
keywords: Biofilm; Osseointegration; Streptococcal collagen mimetic proteins; Titanium implants