The hip bone's connected to the orthopaedic implant [electronic resource] : photoactive elastin-like protein coatings to improve the function of implants

A vast array of implants are employed clinically to interface directly with living bone. These implants include orthopaedic prostheses, such as artificial hip and knee replacements, orthopaedic bone screws, and dental implants and are commonly made from titanium and its alloys. Over one million joint replacements and screws are implanted each year in the United States. In order for these implants to function successfully, they require strong osseointegration, the stable and functional connection between the implant and bone. Unfortunately, approximately 10% of implants fail prematurely, and many of these failures are due to poor osseointegration leading to implant loosening. Failures also occur due to microbial infection, which can be severely debilitating to the patient and may necessitate the removal of the implant. Approximately 1-3% of implants become infected, creating a large burden for the patients and the healthcare system. In this work, a versatile coating technology for bone-interfacing implants is developed to improve implant osseointegration and to provide defense from microbial infection. The coatings are derived from an engineered, elastin-like protein (ELP) that is recombinantly expressed in Escherichia coli. The ELP contains functional domains from two natural extracellular matrix proteins - elastin and fibronectin - to confer specific mechanical and biochemical properties, respectively. The elastin-like domain provides mechanical toughness and resiliency, while the fibronectin-derived RGD domain is cell-adhesive. Thin-film coatings made from ELP can be processed by a variety of methods to coat implants of any shape or size. To stabilize the coatings and adhere them to implant surfaces, a novel covalent crosslinking strategy is employed. Lysine residues are strategically substituted into the elastin-like domains to provide sites for chemical modification of the ELP through the primary amines present on the lysine side chains. A photoactive heterobifunctional crosslinker, NHS-diazirine, is conjugated through these primary amines, rendering the ELP photocrosslinkable upon exposure to ultraviolet (UV) light. The activated diazirine moiety interposes into neighboring bonds, leading to a covalently crosslinked ELP hydrogel. Furthermore, the diazirine can also covalently conjugate to common implant materials through the same UV-mediated mechanism, thereby creating a stable ELP thin-film coating with strong adhesion to implants. Good osseointegration of implants reduces the chance of aseptic loosening while poor osseointegration allows for micromotion of the implant relative to the bone, causing wear, inflammation, and implant loosening. By encouraging new bone deposition on the implant surface, osseointegration can be improved by stabilizing the bone-implant interface. The ELP coatings are able to enhance osseointegration by interacting with native osteogenic cells, including osteoblasts and mesenchymal stem cells (MSCs) through the RGD ligand. The presence of the ligand facilitates rapid cell adhesion, and the ELP coatings demonstrate the ability to improve osteogenic differentiation and bone mineral deposition in vitro, key steps for new bone formation and improved osseointegration. The coatings also improve osseointegration markers in vivo. Microbial infection is another leading cause of implant failure. Bacteria readily adhere to implant surfaces and form biofilms resistant to systemic antibiotic treatments, necessitating alternative strategies to prevent and treat implant-site infections. The antimicrobial properties of silver have long been known, and here it is employed as a localized defense against infection by incorporating silver chloride nanoparticles into the ELP coatings. These antimicrobial coatings rapidly kill over 95% of Staphylococcus aureus, the most common implant pathogen. The achievements presented in this work demonstrate significant advancements for implant coating technologies and have strong potential for clinical translation to improve implant function, lifetime, and efficacy.

Keywords: Materials Science and Engineering.
Advisor: Heilshorn Sarah primary advisor. Thesis advisor
Goodman Stuart
Melosh Nicholas A. advisor. Thesis advisor