Silicon Oxynitrophosphide Nanoscale Coating Enhances Antioxidant Marker-Induced Angiogenesis During in vivo Cranial Bone-Defect Healing.

Critical-sized bone defects are challenging to heal because of the sudden and large volume of lost bone. Fixative plates are often used to stabilize defects, yet oxidative stress and delayed angiogenesis are contributing factors to poor biocompatibility and delayed bone healing. This study tests the angiogenic and antioxidant properties of amorphous silicon oxynitrophosphide (SiONPx) nanoscale-coating material on endothelial cells to regenerate vascular tissue in vitro and in bone defects.

Elevation of Proinflammatory Cytokine HMGB1 in the Synovial Fluid of Patients With Legg-Calvé-Perthes Disease and Correlation With IL-6.

Legg-Calvé-Perthes disease (LCPD) is a childhood ischemic osteonecrosis (ON) of the femoral head associated with the elevation of proinflammatory cytokine interleukin-6 (IL-6) in the synovial fluid. Currently, there is no effective medical therapy for patients with LCPD. In animal models of ischemic ON, articular chondrocytes produce IL-6 in response to ischemic ON induction and IL-6 receptor blockade improves bone healing.

Anti-Interleukin-6 Therapy Decreases Hip Synovitis and Bone Resorption and Increases Bone Formation Following Ischemic Osteonecrosis of the Femoral Head.

Legg-Calvé-Perthes disease (LCPD) is a juvenile form of ischemic femoral head osteonecrosis, which produces chronic hip synovitis, permanent femoral head deformity, and premature osteoarthritis. Currently, there is no medical therapy for LCPD. Interleukin-6 (IL-6) is significantly elevated in the synovial fluid of patients with LCPD.

Analysis of Trabecular Microstructure and Vascular Distribution of Capital Femoral Epiphysis Relevant to Legg-Calve-Perthes Disease.

Legg-Calve-Perthes disease is characterized by the capital femoral epiphyseal collapse, which occurs more reliably in the anterior quadrant than the more weight-bearing lateral quadrant. The purpose of this study was to determine whether there is a vascular or microstructural predisposition for anterior femoral epiphyseal collapse in Perthes disease. Thirty-two cadaveric proximal femoral epiphyses from 17 subjects (age 4-14 years old) underwent micro-computed tomography at 10-μm resolution.

Targeted Disruption of NF1 in Osteocytes Increases FGF23 and Osteoid With Osteomalacia-like Bone Phenotype.

Neurofibromatosis type 1 (NF1, OMIM 162200), caused by NF1 gene mutations, exhibits multi-system abnormalities, including skeletal deformities in humans. Osteocytes play critical roles in controlling bone modeling and remodeling. However, the role of neurofibromin, the protein product of the NF1 gene, in osteocytes is largely unknown.

Assessment of Femoral Head Revascularization in Legg-Calvé-Perthes Disease Using Serial Perfusion MRI.

Background: Legg-Calvé-Perthes disease is a juvenile form of osteonecrosis of the femoral head. The purpose of this study was to use serial perfusion magnetic resonance imaging (MRI) to determine the pattern and rate of revascularization of the femoral heads of patients with the active stage of Legg-Calvé-Perthes disease.

Methods: We performed a prospective study of 29 patients (30 hips) with a mean age (and standard deviation) of 8.

Targeted disruption of BMP signaling through type IA receptor (BMPR1A) in osteocyte suppresses SOST and RANKL, leading to dramatic increase in bone mass, bone mineral density and mechanical strength.

Recent studies suggest a critical role of osteocytes in controlling skeletal development and bone remodeling although the molecular mechanism is largely unknown. This study investigated BMP signaling in osteocytes by disrupting Bmpr1a under the Dmp1-promoter. The conditional knockout (cKO) mice displayed a striking osteosclerotic phenotype with increased trabecular bone volume, thickness, number, and mineral density as assessed by X-ray and micro-CT.

HIF-1-Dependent IL-6 Activation in Articular Chondrocytes Initiating Synovitis in Femoral Head Ischemic Osteonecrosis.

Background: Ischemic osteonecrosis of the femoral head in children is associated with chronic hip synovitis and increased levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in the synovial fluid due to unknown mechanisms. The purpose of this study was to investigate hypoxia-inducible factor-1 (HIF-1) activation as a molecular mechanism linking the induction of ischemic osteonecrosis to IL-6 production and the initiation of hip synovitis.

Methods: Ischemic osteonecrosis was surgically induced in the right femoral head of 6 piglets.

Amorphous Silica: A New Antioxidant Role for Rapid Critical-Sized Bone Defect Healing.

Traumatic fractures cause structurally unstable sites due to severe bone loss. Such fractures generate a high yield of reactive oxygen species (ROS) that can lead to oxidative stress. Excessive and prolonged ROS activity impedes osteoblast differentiation and instigates long healing times.

Intraosseous Delivery of Bone Morphogenic Protein-2 Using a Self-Assembling Peptide Hydrogel.

Osteonecrosis of the femoral head (ONFH) is a debilitating hip disorder, which often produces a permanent femoral head deformity and osteoarthritis. The local delivery of biological agents capable of stimulating bone healing offer potential new treatment options for patients with ONFH. Previous studies from our laboratory have shown that a local intraosseous infusion of bone morphogenic protein-2 (BMP-2) was effective in stimulating new bone formation in a piglet model of ischemic ONFH.

Comprehensive Genome-Wide Transcriptomic Analysis of Immature Articular Cartilage following Ischemic Osteonecrosis of the Femoral Head in Piglets.

Objective: Ischemic osteonecrosis of the femoral head (ONFH) in piglets results in an ischemic injury to the immature articular cartilage. The molecular changes in the articular cartilage in response to ONFH have not been investigated using a transcriptomic approach. The purpose of this study was to perform a genome-wide transcriptomic analysis to identify genes that are upregulated in the immature articular cartilage following ONFH.

Two novel high performing composite PMMA-CaP cements for vertebroplasty: An ex vivo animal study.

There is a growing body of the literature on new cement formulations that address the shortcomings of PMMA bone cements approved for use in vertebroplasty (VP) and balloon kyphoplasty (BKP). The present study is a contribution to these efforts by further characterization of two pre-mixed CaP filler-reinforced PMMA bone cements intended for VP; namely, PMMA-HA and PMMA-brushite cements. Each of these cements showed acceptable levels of various properties determined in porcine vertebral bodies.

Enhanced interfacial adhesion and osteogenesis for rapid "bone-like" biomineralization by PECVD-based silicon oxynitride overlays.

Structurally unstable fracture sites require metal fixative devices, which have long healing times due to their lack of osteoinductivity. Bioactive glass coatings lack in interfacial bonding, delaminate, and have reduced bioactivity due to the high temperatures used for their fabrication. Here, we test the hypothesis that low-temperature PECVD amorphous silica can enhance adhesion to the underlying metal surface and that N incorporation enhances osteogenesis and rapid biomineralization.

In vivo monitoring of activated macrophages and neutrophils in response to ischemic osteonecrosis in a mouse model.

Ischemic osteonecrosis (IO) is caused by disruption of the blood supply to bone. It is a debilitating condition with pathological healing characterized by excessive bone resorption and delayed osteogenesis. Although the majority of research has focused on the role of osteoblasts and osteoclasts in the disease progression, we hypothesize that innate immune cells, macrophages and neutrophils, play a significant role.

Interobserver and intraobserver reliability of the modified Waldenström classification system for staging of Legg-Calvé-Perthes disease.

Background: The absence of a reliable classification system for Legg-Calvé-Perthes disease has contributed to difficulty in establishing consistent management strategies and in interpreting outcome studies. The purpose of this study was to assess interobserver and intraobserver reliability of the modified Waldenström classification system among a large and diverse group of pediatric orthopaedic surgeons.

Methods: Twenty surgeons independently completed the first two rounds of staging: two assessments of forty deidentified radiographs of patients with Legg-Calvé-Perthes disease in various stages.

Development of a mouse model of ischemic osteonecrosis.

Background: Availability of a reliable mouse model of ischemic osteonecrosis could accelerate the development of novel therapeutic strategies to stimulate bone healing after ischemic osteonecrosis; however, no mouse model of ischemic osteonecrosis is currently available.

Questions/purposes: To develop a surgical mouse model of ischemic osteonecrosis, we asked, (1) if the blood vessels that contribute to the blood supply of the distal femoral epiphysis are cauterized, can we generate an osteonecrosis mouse model; (2) what are the histologic changes observed in this mouse model, and (3) what are the morphologic changes in the model.

Methods: We performed microangiography to identify blood vessels supplying the distal femoral epiphysis in mice, and four vessels were cauterized using microsurgical techniques to induce ischemic osteonecrosis.

Bone apatite composition of necrotic trabecular bone in the femoral head of immature piglets.

Ischemic osteonecrosis of the femoral head (IOFH) can lead to excessive resorption of the trabecular bone and collapse of the femoral head as a structure. A well-known mineral component to trabecular bone is hydroxyapatite, which can be present in many forms due to ionic substitution, thus altering chemical composition. Unfortunately, very little is known about the chemical changes to bone apatite following IOFH.

Human periosteum cell osteogenic differentiation enhanced by ionic silicon release from porous amorphous silica fibrous scaffolds.

Current synthetic grafts for bone defect filling in the sinus can support new bone formation but lack the ability to stimulate or enhance osteogenic healing. To promote such healing, osteoblast progenitors such as human periosteum cells must undergo osteogenic differentiation. In this study, we tested the hypothesis that degradation of porous amorphous silica fibrous (PASF) scaffolds can enhance human periosteum cell osteogenic differentiation.

Decreasing NF-κB expression enhances odontoblastic differentiation and collagen expression in dental pulp stem cells exposed to inflammatory cytokines.

Inflammatory response in the dental pulp can alter the collagen matrix formation by dental pulp stem cells and lead to a delay or poor healing of the pulp. This inflammatory response is mediated by cytokines, including interleukin-1β and tumor necrosis factor-α. In this study, it is hypothesized that suppressing the actions of these inflammatory cytokines by knocking down the activity of transcription factor Nuclear Factor-κB will lead to dental pulp stem cell differentiation into odontoblasts and the production of collagen.

Legg-Calvé-Perthes disease produces chronic hip synovitis and elevation of interleukin-6 in the synovial fluid.

Legg-Calvé-Perthes disease (LCPD) is a childhood hip disorder of ischemic osteonecrosis of the femoral head. Hip joint synovitis is a common feature of LCPD, but the nature and pathophysiology of the synovitis remain unknown. The purpose of this study was to determine the chronicity of the synovitis and the inflammatory cytokines present in the synovial fluid at an active stage of LCPD.

Quantitative assessment of synovitis in Legg-Calvé-Perthes disease using gadolinium-enhanced MRI.

A quantitative method to assess hip synovitis in Legg-Calvé-Perthes disease (LCPD) is not currently available. To develop this method, the areas of synovial enhancement on gadolinium-enhanced MRI (Gd-MRI) were measured by two independent observers. The volume of synovial enhancement was significantly increased in the initial and the fragmentation stages of LCPD (Waldenström stages I and II), with a persistence of synovitis into the reossification stage (stage III).

Local administration of bone morphogenetic protein-2 and bisphosphonate during non-weight-bearing treatment of ischemic osteonecrosis of the femoral head: an experimental investigation in immature pigs.

Background: Non-weight-bearing decreases the femoral head deformity but increases bone resorption without increasing bone formation in an experimental animal model of Legg-Calvé-Perthes disease. We sought to determine if local administration of bone morphogenetic protein (BMP)-2 with or without bisphosphonate can increase the bone formation during the non-weight-bearing treatment in the large animal model of Legg-Calvé-Perthes disease.

Methods: Eighteen piglets were surgically induced with femoral head ischemia.