Murine models of orthopedic infection featuring biofilm.

: Osteomyelitis remains a major clinical challenge. Many published rodent fracture infection models are costly compared with murine models for rapid screening and proof-of-concept studies. We aimed to develop a dependable and cost-effective murine bone infection model that mimics bacterial bone infections associated with biofilm and metal implants.

Modeling anabolic and antiresorptive therapies for fracture healing in a mouse model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a genetic bone fragility disorder that features frequent fractures. Bone healing outcomes are contingent on a proper balance between bone formation and resorption, and drugs such as bone morphogenetic proteins (BMPs) and bisphosphonates (BPs) have shown to have utility in modulating fracture repair. While BPs are used for OI to increase BMD and reduce pain and fracture rates, there is little evidence for using BMPs as local agents for fracture healing (alone or with BPs).

Modulation of spine fusion with BMP-2, MEK inhibitor (PD0325901), and zoledronic acid in a murine model of NF1 double inactivation.

Background: Spine fusion is a common procedure for the treatment of severe scoliosis, a frequent and challenging deformity associated with Neurofibromatosis type 1 (NF1). Moreover, deficiencies in NF1-Ras-MEK signaling affect bone formation and resorption that in turn impacts on spine fusion outcomes.

Methods: In this study we describe a new model for AdCre virus induction of Nf1 deficiency in the spines of Nf1 mice.

A novel task for examining the neural basis of Theory of Mind deficits in bipolar disorder.

Deficits in theory of mind (ToM) processing have been observed in people with bipolar disorder (BD), but the neural basis of these deficits remains unclear. Here, we studied the relations between neural activation, dysfunctional beliefs and behavioral responses in people with BD during a second-order ToM task. Twenty-five patients and 25 healthy-control participants (HC) underwent functional magnetic resonance imaging (fMRI) while performing a novel ToM task.

Preclinical models for orthopedic research and bone tissue engineering.

In this review, we broadly define and discuss the preclinical rodent models that are used for orthopedics and bone tissue engineering. These range from implantation models typically used for biocompatibility testing and high-throughput drug screening, through to fracture and critical defect models used to model bone healing and severe orthopedic injuries. As well as highlighting the key methods papers describing these techniques, we provide additional commentary based on our substantive practical experience with animal surgery and in vivo experimental design.

Homozygous Dkk1 Knockout Mice Exhibit High Bone Mass Phenotype Due to Increased Bone Formation.

Wnt antagonist Dkk1 is a negative regulator of bone formation and Dkk1 heterozygous mice display a high bone mass phenotype. Complete loss of Dkk1 function disrupts embryonic head development. Homozygous Dkk1 mice that were heterozygous for Wnt3 loss of function mutation (termed Dkk1 KO) are viable and allowed studying the effects of homozygous inactivation of Dkk1 on bone formation.

Implant-delivered Alendronate Causes a Dose-dependent Response on Net Bone Formation Around Porous Titanium Implants in Canines.

Background: Bony fixation of cementless orthopaedic implants is not always achieved, particularly in challenging scenarios such as revision surgery, trauma, and tumor reconstruction. An adjunct therapy for improving porous implant fixation could improve the reliability and durability of these reconstructive procedures.

Questions/purposes: In this study, we asked whether there is a positive and dose-dependent effect of the local release of the bisphosphonate alendronate from (1) alendronate/hydroxyapatite (HA) porous-coated titanium implants compared with bare metal porous controls; and (2) alendronate/HA on porous-coated titanium implants compared with HA-coated porous controls with respect to extent of bone ingrowth, bone apposition, and periimplant bone formation in a canine model?

Methods: Three-dimensional printed porous-coated cylindrical implants coated with three different doses (0.

Lineage tracking of mesenchymal and endothelial progenitors in BMP-induced bone formation.

To better understand the relative contributions of mesenchymal and endothelial progenitor cells to rhBMP-2 induced bone formation, we examined the distribution of lineage-labeled cells in Tie2-Cre:Ai9 and αSMA-creERT2:Col2.3-GFP:Ai9 reporter mice. Established orthopedic models of ectopic bone formation in the hind limb and spine fusion were employed.

Animal models of scoliosis.

Multiple techniques designed to induce scoliotic deformity have been applied across many animal species. We have undertaken a review of the literature regarding experimental models of scoliosis in animals to discuss their utility in comprehending disease aetiology and treatment. Models of scoliosis in animals can be broadly divided into quadrupedal and bipedal experiments.

Use of induced pluripotent stem cell derived neurons engineered to express BDNF for modulation of stressor related pathology.

Combined cell and gene-based therapeutic strategies offer potential in the treatment of neurodegenerative and psychiatric conditions that have been associated with structural brain disturbances. In the present investigation, we used a novel virus-free re-programming method to generate induced pluripotent stem cells (iPSCs), and then subsequently transformed these cells into neural cells which over-expressed brain derived neurotrophic factor (BDNF). Importantly, the infusion of iPSC derived neural cells (as a cell replacement and gene delivery tool) and BDNF (as a protective factor) influenced neuronal outcomes.

Maximizing bone formation in posterior spine fusion using rhBMP-2 and zoledronic acid in wild type and NF1 deficient mice.

Spinal pseudarthrosis is a well described complication of spine fusion surgery in NF1 patients. Reduced bone formation and excessive resorption have been described in NF1 and anti-resorptive agents may be advantageous in these individuals. In this study, 16 wild type and 16 Nf1(+/-) mice were subjected to posterolateral fusion using collagen sponges containing 5 µg rhBMP-2 introduced bilaterally.

Interaction between nonviral reprogrammed fibroblast stem cells and trophic factors for brain repair.

There are currently no known treatment options that actually halt or permanently reverse the pathology evident in any neurodegenerative condition. Arguably, one of the most promising avenues for creating viable neuronal treatments could involve the combined use of cell replacement and gene therapy. Given the complexity of the neurodegenerative process, it stands to reason that adequate therapy should involve not only the replacement of loss neurons/synapses but also the interruption of multiple pro-death pathways.

Local alendronic acid elution increases net periimplant bone formation: a micro-CT analysis.

Background: Fixation of cementless orthopaedic implants is not always achieved, particularly in challenging scenarios such as revision surgery, trauma, and tumor reconstruction. An adjunct therapy for improving implant fixation would improve the reliability and durability of certain reconstructive procedures.

Questions/purposes: The purpose of this study was to determine the effect of local elution of the bisphosphonate alendronic acid on bone formation around porous titanium implants in an animal model.

Posterolateral inter-transverse lumbar fusion in a mouse model.

Background: Spinal fusion is a common orthopaedic procedure that has been previously modeled using canine, lapine, and rodent subjects. Despite the increasing availability of genetically modified mouse strains, murine models have only been infrequently described.

Purpose: To present an efficient and minimally traumatic procedure for achieving spinal fusion in a mouse model and determine the optimal rhBMP-2 dose to achieve sufficient fusion mass.

Stressor-like effects of c-Jun N-terminal kinase (JNK) inhibition.

There is an urgent need for novel treatment strategies for stressor related disorders, particularly depression and anxiety disorders. Indeed, existing drug treatments are only clinically successful in a subset of patients and relapse is common. This likely stems from the fact that stressor disorders are heterogeneous with multiple biological pathways being affected.

Viral-toxin interactions and Parkinson's disease: poly I:C priming enhanced the neurodegenerative effects of paraquat.

Background: Parkinson's disease (PD) has been linked with exposure to a variety of environmental and immunological insults (for example, infectious pathogens) in which inflammatory and oxidative processes seem to be involved. In particular, epidemiological studies have found that pesticide exposure and infections may be linked with the incidence of PD. The present study sought to determine whether exposure to a viral mimic prior to exposure to pesticides would exacerbate PD-like pathology.

A murine model of neurofibromatosis type 1 tibial pseudarthrosis featuring proliferative fibrous tissue and osteoclast-like cells.

Neurofibromatosis type 1 (NF1) is a common genetic condition caused by mutations in the NF1 gene. Patients often suffer from tissue-specific lesions associated with local double-inactivation of NF1. In this study, we generated a novel fracture model to investigate the mechanism underlying congenital pseudarthrosis of the tibia (CPT) associated with NF1.

The Otto Aufranc Award: Demineralized bone matrix around porous implants promotes rapid gap healing and bone ingrowth.

Background: Noncemented revision arthroplasty is often complicated by the presence of bone implant gaps that reduce initial stability and biologic fixation. Demineralized bone matrix has osteoinductive properties and therefore the potential to enhance gap healing and porous implant fixation.

Questions/purposes: We determined at what times and to what extent demineralized bone matrix promotes gap healing and bone ingrowth around a porous implant.

Interferon-γ plays a role in paraquat-induced neurodegeneration involving oxidative and proinflammatory pathways.

Exposure to environmental contaminants, particularly pesticides, may be an important etiological factor in Parkinson's disease (PD); and evidence suggests a role for microglia-dependent inflammatory and oxidative processes in nigrostriatal pathology induced by such toxins. Yet, the events mediating microglial activation and their effects are not fully known. To this end, we hypothesized that the proinflammatory cytokine, interferon-gamma (IFN-γ), may be a prime factor in the pathogenesis of PD, given its critical role in regulating microglial responses to pathogens.

Granulocyte macrophage-colony stimulating factor protects against substantia nigra dopaminergic cell loss in an environmental toxin model of Parkinson's disease.

Parkinson's disease (PD) has been linked to exposure to a variety of chemical (e.g., pesticides) and inflammatory agents, which may act cumulatively over time.

Inflammatory mechanisms of neurodegeneration in toxin-based models of Parkinson's disease.

Parkinson's disease (PD) has been associated with exposure to a variety of environmental agents, including pesticides, heavy metals, and organic pollutants; and inflammatory processes appear to constitute a common mechanistic link among these insults. Indeed, toxin exposure has been repeatedly demonstrated to induce the release of oxidative and inflammatory factors from immunocompetent microglia, leading to damage and death of midbrain dopamine (DA) neurons. In particular, proinflammatory cytokines such as tumor necrosis factor-α and interferon-γ, which are produced locally within the brain by microglia, have been implicated in the loss of DA neurons in toxin-based models of PD; and mounting evidence suggests a contributory role of the inflammatory enzyme, cyclooxygenase-2.

Interprofessional continuing health education for diabetic patients in an urban underserved community.

The CPD(iQ) Saskatchewan Project (ICEC(4)) is directed by the Inter-Professional Continuing Education for Collaborative Client Centered Care Committee, representing the disciplines of medicine, nursing, physical therapy, pharmacy, kinesiology and dentistry at the University of Saskatchewan. It was designed to serve two target audiences: the urban underserved community that would access services at the West Winds Primary Care Centre; and health professionals at the West Winds who would deliver educational modules to those in need. The main objectives were to identify the learning needs of health professionals related to working collaboratively in urban underserved community settings; identify and develop relevant educational modules to address needs identified, implement the program, and evaluate participants' experience with the educational modules.

Histopathologic retrieval analysis of clinically failed porous tantalum osteonecrosis implants.

Background: An Osteonecrosis Intervention Implant made of porous tantalum was recently developed to provide structural support and a compatible surface for tissue ingrowth in osteonecrotic femoral heads. From an investigational device exemption study that comprised 113 implants, we carried out a retrieval analysis of clinically failed implants.

Methods: Seventeen porous tantalum implants that had been used for the treatment of Steinberg stage-II osteonecrosis of the hip were retrieved at the time of conversion to a total hip arthroplasty.

The response of mineralizing culture systems to microtextured and polished titanium surfaces.

The surface texture of titanium has a predictable effect on peri-implant tissue formation in vivo. When implanted in an osseous environment, smooth surfaces (R(a) < 0.5 mm) are generally apposed by fibrous tissue and textured surfaces (R(a) > 1.