Nanocoating Technology May Prevent Spinal Implant Infections Without Inhibiting Osseointegration

All orthopaedic implants in the spine will be exposed to bacteria during or following implantation, with the first 24 hours after spine surgery being the most crucial to preventing biofilm formation, explained Gregory Lutz, MD. Given the paradigm shift in current understanding of the potential role of occult infection in aseptic loosening of spinal instrumentation, research has focused on building an antimicrobial surface coating for spinal implants that offer minimal risk and maximum reward.
Gregory Lutz, MD likened the prevention of bacterial contamination of spinal implants as a “race to the surface.”A Race to the Surface
Dr. Lutz likened the prevention of bacterial contamination of spinal implants as a “race to the surface. If the bacterial cells get to the implant surface first and set in a biofilm, then host cells can’t create a good bond and close the gap into normal tissue, and vice versa. Studies have shown that better osseointegration leads to a lower infection rate,” said Dr. Lutz, who is Co-Founder and Chairman of Orthobond Corporation and Physiatrist-In-Chief Emeritus at Hospital for Special Surgery in New York City.

Emerging technologies are geared toward changing the device interface using drug-eluting technologies and non-eluting technologies. Drug-eluting technologies present challenges in terms of securing FDA approval as well as the potential for antibacterial agents to inhibit osseointegration.

In addition, some of the non-eluting surfaces that have anti-adhesion/anti-adsorption properties also may inhibit osseointegration. Inorganic surfaces such as silver may pose toxicity issues, and antimicrobials that are added onto non-eluting surfaces may not stay on the surface after implantation or may become inactive when tethered to the biomaterial because the binding site is usually the active site of the antibiotic, Dr. Lutz explained.

The Ideal Spinal Implant Coating
The characteristics of an ideal orthopaedic implant coating are as follows, according to Dr. Lutz:

• Non-polymer
• Covalently attached safe antimicrobial agent
• Oligodynamic effect creating broad-spectrum kill
• Does not foster resistance
• Biocompatible or enhances osseointegration
• Protects underlying biomaterial from oxidation
• Easily applied, cost-efficient, and scalable processing
• Stable to mechanical, hydrolytic, enzymatic and sterilization forces
• Can be applied to a wide variety of biomaterials
• Does not change underlying surface geometry

“We believe that nanotechnology offers a potential solution, whether it is a nanotextured surface or a nanocoating, which is 1/100^th the width of the size of a piece of hair,” Dr. Lutz said.

Nanocoating Technology is Antimicrobial and Without Inhibiting Osseointegration
Dr. Lutz and his colleagues at Orthobond have developed a technology to attach biomolecules to orthopaedic implants. The technology involves covalent attachment of phosphonic acid to a variety of implants (eg, titanium, titanium alloys, cobalt chrome, and stainless steel). Antimicrobial agents, or any other organic molecules, can then be added on top of this phosphonate monolayer.

“The technology creates a transformative surface allowing the inorganic material to become an organic site to bond to in a stable fashion,” Dr. Lutz said. The surface is 1 to 2 nanometers thick and, thus, does not change the surface geometry.

Dr. Lutz and colleagues screened more than 1,000 linker-agent antimicrobial candidates and determined that quaternary ammonium compounds (QACs) are best as they retain their activity when covalently bound to biomaterial surfaces. QACs disrupt cell walls and kill bacteria, viruses, molds, and fungi. These compounds are used in household products such as shampoos, mouthwashes, and disinfectants.

In vitro screening assays of the antimicrobial nanocoating demonstrates a 91% to 99% kill rate against a variety of Gram-negative and Gram-positive aerobes and anaerobes. The kill rate for Propionibacterium acne (P. acne) for example, was 95%. Antibiotic susceptibility testing for 10 successive exposures over a 5-week period showed no evidence of S. aureus or E. coli resistance.

In vivo testing in an animal model showed no infection in surrounding tissue or the antimicrobial nanocoated implants when extracted at 5 days. Compared with an uncoated control implant, there was a “99% reduction in CFUs [colony forming units] of bacteria with the treated implant,” Dr. Lutz said. In addition, osseointegration has been normal in both rabbit and sheep models implanted with coated devices, he said.

“Our antimicrobial nanocoatings are non-polymer, and they covalently attach a safe antimicrobial agent,” Dr. Lutz concluded. “The implant nanocoatings are stable to mechanical, hydrolytic, enzymatic, and sterilization forces, and create an oligodynamic effect creating broad-spectrum  kill. They do not foster resistance. They are biocompatible and allow for normal osseointegration and protect the underlying biomaterial from oxidation.”

Other presentations related to this symposium:

• Do Occult Pathogens Play a Role in Failed Back Surgery?
• Preventing Spinal Implant Contamination in Spine Surgery
• Infections in Spine Surgery: The Role of Occult Pathogens

Disclosure
Dr. Lutz is Co-Founder and Chairman of Orthobond Corporation and is Chief Medical Advisor for Spine Medicine at BioRestorative Therapies, Inc.