Magnetic nanoparticles (MNPs) have a wide range of applications; an area of particular interest is magnetic particle imaging (MPI). MPI is an imaging modality that utilizes superparamagnetic iron oxide particles (SPIONs) as tracer particles to produce highly sensitive and specific images in a broad range of applications, including cardiovascular, neuroimaging, tumor imaging, magnetic hyperthermia and cellular tracking. While there are hurdles to overcome, including accessibility of products, and an understanding of safety and toxicity profiles, MPI has the potential to revolutionize research and clinical biomedical imaging. This review will explore a brief history of MPI, MNP synthesis methods, current and future applications, and safety concerns associated with this newly emerging imaging modality.
Osteomyelitis is an inflammatory bone disease typically caused by infectious microorganisms, often bacteria, which causes progressive bone destruction and loss. The most common bacteria associated with chronic osteomyelitis is Staphylococcus aureus. The incidence of osteomyelitis in the United States is estimated to be upwards of 50,000 cases annually and places a significant burden upon the healthcare system. There are three general categories of osteomyelitis: hematogenous; secondary to spread from a contiguous focus of infection, often from trauma or implanted medical devices and materials; and secondary to vascular disease, often a result of diabetic foot ulcers. Independent of the route of infection, osteomyelitis is often challenging to diagnose and treat, and the effect on the patient's quality of life is significant. Therapy for osteomyelitis varies based on category and clinical variables in each case. Therapeutic strategies are typically reliant upon protracted antimicrobial therapy and surgical interventions. Therapy is most successful when intensive and initiated early, although infection may recur months to years later. Also, treatment is accompanied by risks such as systemic toxicity, selection for antimicrobial drug resistance from prolonged antimicrobial use, and loss of form or function of the affected area due to radical surgical debridement or implant removal. The challenges of diagnosis and successful treatment, as well as the negative impacts on patient's quality of life, exemplify the need for improved strategies to combat bacterial osteomyelitis. There are many in vitro and in vivo investigations aimed toward better understanding of the pathophysiology of bacterial osteomyelitis, as well as improved diagnostic and therapeutic strategies. Here, we review the role of animal models utilized for the study of bacterial osteomyelitis and their critically important role in understanding and improving the management of bacterial osteomyelitis.
The biodegradable nature of magnesium in aqueous mediums makes it an attractive material for various biomedical applications when it is not recommended that the material stay permanently in the body. Some of the main challenges that hinder the use of magnesium for bone fracture repair are its limited mechanical strength and fast corrosion rates. To this end, we developed a novel Mg-Zn-Ca-Mn-based alloy and post-fabrication methods that can deliver high-strength and corrosion-controlled implant materials to address these challenges. This study is focused on assessing the in vitro corrosion and in vivo biocompatibility of the developed magnesium-based alloy and post-fabrication processes. The developed heat treatment process resulted in an increase in the microhardness from 71.9 ± 5.4 HV for the as-cast Mg alloy to as high as 98.1 ± 6.5 HV for the heat-treated Mg alloy, and the ceramic coating resulted in a significant reduction in the corrosion rate from 10.37 mm/yr for the uncoated alloy to 0.03 mm/yr after coating. The in vivo assessments showed positive levels of biocompatibility in terms of degradation rates and integration of the implants in a rabbit model. In the rabbit studies, the implants became integrated into the bone defect and showed minimal evidence of an immune response. The results of this study show that it is possible to produce biocompatible Mg-based implants with stronger and more corrosion-controlled properties based on the developed Mg-Zn-Ca-Mn-based alloy and post-fabrication methods.
As medicine advances and physicians are able to provide patients with innovative solutions, including placement of temporary or permanent medical devices that drastically improve quality of life of the patient, there is the persistent, recurring problem of chronic bacterial infection, including osteomyelitis. Osteomyelitis can manifest as a result of traumatic or contaminated wounds or implant-associated infections. This bacterial infection can persist as a result of inadequate treatment regimens or the presence of biofilm on implanted medical devices. One strategy to mitigate these concerns is the use of implantable medical devices that simultaneously act as local drug delivery devices (DDDs). This classification of device has the potential to prevent or aid in clearing chronic bacterial infection by delivering effective doses of antibiotics to the area of interest and can be engineered to simultaneously aid in tissue regeneration. This review will provide a background on bacterial infection and current therapies as well as current and prospective implantable DDDs, with a particular emphasis on local DDDs to combat bacterial osteomyelitis.
Surgical site infections (SSIs) are a common complication following orthopedic surgery. SSIs may occur secondary to traumatic or contaminated wounds or may result from invasive procedures. The development of biofilms is often associated with implanted materials used to stabilize injuries and to facilitate healing. Regardless of the source, SSIs can be challenging to treat. This has led to the development of devices that act simultaneously as local antibiotic delivery vehicles and as scaffolds for tissue regeneration. The goal for the aforementioned devices is to increase local drug concentration in order to enhance bactericidal activity while reducing the risk of systemic side effects and toxicity from the administered drug. The aims of this study were to assess the effect of antibiotic loading of a collagen matrix on the tissue integration of the matrix using a rat mandibular defect model. We hypothesized that the collagen matrix could load and elute gentamicin, that the collagen matrix would be cytocompatible in vitro, and that the local delivery of a high dose of gentamicin via loaded collagen matrix would negatively impact the tissue–scaffold interface. The results indicate that the collagen matrix could load and elute the antimicrobial gentamicin and that it was cytocompatible in vitro with or without the presence of gentamicin and found no significant impact on the tissue–scaffold interface when the device was loaded with a high dose of gentamicin.
24 November 2022 in Frontiers in Cellular and Infection Microbiology
Staphylococcus aureus (SA) is a significant and well-recognized causative organism of bacterial osteomyelitis. Osteomyelitis is an inflammatory bone disease characterized by progressive bone destruction and loss. This disease causes significant morbidity and mortality to the patient and poses therapeutic challenges for clinicians. To improve the efficacy of therapeutic strategies to combat bacterial osteomyelitis, there is a need to define the molecular epidemiology of bacterial organisms more clearly and further the understanding of the pathogenesis of SA osteomyelitis. We conducted in vitro characterization of the pathogenic capabilities of an isolate of SA ST398 derived from a clinical case of osteomyelitis in a goat. We also report a rodent mandibular defect model to determine the ability of ST398 to cause reproducible osteomyelitis. Our results indicate that ST398 can invade and distort pre-osteoblastic cells in culture, induce significant inflammation and alter expression of osteoregulatory cytokines. We also demonstrate the ability of ST398 to induce osteomyelitis in a rat mandibular model. When compiled, these data support ST398 as a competent osteomyelitis pathogen.