Innovative Implant Nanocoatings with Controlled Dual Drug Release for Bone Regeneration
Abstract
Open fractures, where bone protrudes through the skin, are commonly seen in civilian and military personnel. It is estimated that more than 150,000 open fractures occur in the U.S. every year; open fractures are increasingly common. Intramedullary (IM) nailing, which is placing a rod down the bone canal, has been widely used to fix open fractures; delays in fracture healing and infection are two major complications associated with this type of fixation. The objective of this application is to develop controlled release of substances to reduce the two major complications mentioned above. One substance is a growth factor called recombinant human bone morphogenetic protein 2 or rhBMP-2, which helps bone to grow and a fracture to heal. The other substance is an antibacterial agent (interleukin-12p70 or IL-12) that occurs naturally in the human body and helps fight infection. Nanocoatings are extremely thin layers on the nanoscale; we will develop nanocoatings with controlled release of these drugs on implants used to fix fractures. The primary hypothesis of this application is that controlled release of rhBMP-2 (which may lead to enhanced bone growth and provide a seal to protect against bacterial attachment) and IL-12 (a natural substance that the preliminary data showed to have antimicrobial or bacteria-fighting properties) will lead to improved bone growth and reduced infection. Two specific aims are proposed: Specific Aim 1: To create multilayer nanocoatings for controlled loading and release of rhBMP-2 and IL-12 after nanocoating preparation. We will develop model implant nanocoatings that combine rhBMP-2 and IL-12 simultaneously at the implant/tissue interface. Multilayer nanocoatings containing capsules that are loaded with polyelectrolytes will be prepared. After completion of nanocoating preparation, both rhBMP-2 and IL-12 will be loaded, and controlled release of both drugs will be obtained. The co-delivery nanocoatings will have their characteristics described: surface form and structure, thickness, stability, drug loading level and efficiency, release properties, and effectiveness of released drugs. Specific Aim 2: To determine the effectiveness of the co-delivery nanocoatings in stimulating bone growth and in reducing bacterial infection in IM nailing of open fractures in an animal model. Co-delivery of rhBMP-2 and IL-12 will be examined in an IM nail open fracture rat model for bone growth, infection reduction, and systemic and local reactions to the substances. Upon completion of the proposed studies, we expect to have developed multilayer nanocoatings on stainless steel wire implants with controlled release of rhBMP-2 and IL-12 and that these nanocoatings led to enhanced bone growth and reduced infection in the IM nail open fracture rat model. The success of the proposed studies will lead to future studies to further examine the dual drug delivery systems in larger animal models and against antibiotic-resistant infections, which are more difficult to treat as they do not respond to the common drugs used to treat them. This application is innovative. Some conventional antibiotic delivery systems require the handling of drugs with heat or damaging solvents so incorporation of heat/solvent sensitive protein drugs like rhBMP-2 and IL-12 has been difficult. Meanwhile, the current state-of-the-art drug-carrying implant coatings are mostly limited to those that load the drug molecules during coating preparation, which, in most cases, results in loss of effectiveness. In this application, multilayer nanocoatings will be prepared in water-based solutions, and the multilayer nanocoatings can load multiple protein drugs after nanocoating preparation (e.g., minutes before surgical implantation inside an operating room); such nanocoatings allow controlled drug release. Moreover, the nanocoatings will reduce two (i.e., delayed bone regeneration and infection) of the major complications of open fr
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710603
Entities
People
- Bingyun Li
Organizations
- United States Army
- West Virginia University