Innovative Nanohybrids with Controlled Drug Release for Bone Regeneration
Abstract
It is known that the success of implants used for trauma fixation etc., depends on the “race-for-the-surface” between the host or patient and bacteria. If the host cells “win” the race then the patient will not get infected; however, if the bacteria “win,” it is likely that the patient will develop an infection following surgery. Ideally, implant surfaces should promote bone growth and prevent infection. In this application, the purpose is to develop new materials called nanohybrids that can help bone to grow and regenerate while preventing infection. These characteristics are a result of controlling the combination and release of nanoparticles, which are tiny components that can be layered onto implant materials. In this study, silicate nanoparticles or SNs will promote bone growth and silver nanoparticles or AgNPs will prevent infection. SNs will be studied because they have been found to promote bone regeneration. AgNPs will be studied because the combination of AgNPs with other nanomaterials has been found to result in improved infection prevention along with significantly improved bone cell viability. AgNPs are less likely to lead to antibiotic resistance. Specifically, nanohybrids of SNs and AgNPs will be created, optimized, and evaluated in a benchtop model and then assessed in a rat open fracture model. The primary hypothesis is that, by controlling materials at the nanometer scale, the unique nanohybrids of SNs and AgNPs will provide significantly improved bone growth/regeneration, strong anti-infection properties, and minimal harm to host cells. Two specific aims are proposed: Aim 1: To create AgNP-SN nanohybrids on orthopaedic implant materials and to examine their ability to promote bone growth, to prevent infection, and to not harm host cells in a benchtop model. AgNP-SN nanohybrids will be prepared and coated on model orthopaedic implants using a layer-by-layer self-assembly technology. The nanohybrid coatings will be studied for surface characteristics, thickness, the stability of the coatings, the level of drugs layered onto and released from the implants, the ability to promote bone growth/regeneration, the ability to prevent infection, and the toxicity or level of harm toward human cells. The effects of the AgNPSN nanohybrid constructs will be examined for bone growth in a specific type of cell called a mesenchymal stem cell, anti-infection properties against a multidrug-resistant bacteria, and the level of harm toward bone cells called osteoblasts. The outcome will be compared with the treatments of SNs and AgNPs alone. Aim 2: To determine whether AgNP-SN nanohybrids will promote bone regeneration and reduce infection in open fractures in a rat model. The AgNP-SN nanohybrids will be studied in an open fracture rat model for bone growth/regeneration, infection, and toxicity. One of the most common drug-resistant bacteria found in bone infections will be used as a model pathogen. Rats will have their thigh bone fractured, infected, fixed with a nanohybrid coated pin in the bone canal, and then they will be euthanized for examination 6 weeks following fracture and repair surgery.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810203
Entities
People
- Bingyun Li
Organizations
- United States Army
- West Virginia University