Vancomycin-Loaded Collagen/Hydroxyapatite Layers Electrospun on 3D Printed Titanium Implants Prevent Bone Destruction Associated with S. epidermidis Infection and Enhance Osseointegration

Abstract

The aim of the study was to develop an orthopedic implant coating in the form of vancomycin-loaded collagen/hydroxyapatite layers (COLHA+V) that combine the ability to prevent bone infection with the ability to promote enhanced osseointegration. The ability to prevent bone infection was investigated employing a rat model that simulated the clinically relevant implant-related introduction of bacterial contamination to the bone during a surgical procedure using a clinical isolate of Staphylococcus epidermidis. The ability to enhance osseointegration was investigated employing a model of a minipig with terminated growth. Six weeks following implantation, the infected rat femurs treated with the implants without vancomycin (COLHA+S. epidermidis) exhibited the obvious destruction of cortical bone as evinced via a cortical bone porosity of up to 20% greater than that of the infected rat femurs treated with the implants containing vancomycin (COLHA+V+S. epidermidis) (3%) and the non-infected rat femurs (COLHA+V) (2%). The alteration of the bone structure of the infected COLHA+S. epidermidis group was further demonstrated by a 3% decrease in the average Ca/P molar ratio of the bone mineral. Finally, the determination of the concentration of vancomycin released into the blood stream indicated a negligible systemic load. Six months following implantation in the pigs, the quantified ratio of new bone indicated an improvement in osseointegration, with a two-fold bone ingrowth on the COLHA (47%) and COLHA+V (52%) compared to the control implants without a COLHA layer (27%). Therefore, it can be concluded that COLHA+V layers are able to significantly prevent the destruction of bone structure related to bacterial infection with a minimal systemic load and, simultaneously, enhance the rate of osseointegration.

Construction of Local Drug Delivery System on Titanium-Based Implants to Improve Osseointegration

“…In addition, Suchý et al constructed Van-loaded collagen/hydroxyapatite layers on the Ti-based implant via electrospun technology and 3D printing technology. They found that the composite coating could prevent the destruction of bone structure caused by bacterial infection and enhance osseointegration [ 79 ].…”

Host Defense Peptide-Mimicking Polymers and Polymeric-Brush-Tethered Host Defense Peptides: Recent Developments, Limitations, and Potential Success

“…Anti-adhesive agents in surface modifications (i.e., hydrophilic polymer brushes) provide coated surfaces that prevent initial bacterial adhesion; however, such architectures do not kill or inhibit biofilm growth, and the few adhered bacteria can over time still form a mature biofilm [181,182]. Therefore, to overcome this shortcoming and improve surface coatings, surface-anchored polymer brushes have been functionalized with antimicrobial agents to kill bacteria and inhibit biofilm development [32,[182][183][184][185].…”

“…Pharmaceutics 2021, 13, x FOR PEER REVIEW 14 of 24 surface coatings, surface-anchored polymer brushes have been functionalized with antimicrobial agents to kill bacteria and inhibit biofilm development [32,[182][183][184][185]. Among these antimicrobial agents, HDPs exhibit appealing features for designing antibiofilm surfaces (Figure 9).…”

Antibacterial and Anti-Inflammatory Coating Materials for Orthopedic Implants: A Review

“…In a rat model, Tomas et al [48] used S. epidermidis to contaminate orthopedic implants and simulate orthopedic implant infection, and added a vancomycin-loaded collagen/hydroxyapatite coating onto 3D-printed titanium (Ti) implants via electrospinning. Finally, the collagen/hydroxyapatite coating loaded with vancomycin was found to significantly kill S. epidermidis, prevent bone damage associated with S. epidermidis infection, and promote bone regeneration and integration.…”