Novel Calcium Phosphate Promotes Interbody Bony Fusion in a Porcine Anterior Cervical Discectomy and Fusion Model.

Study Design: Experimental porcine anterior cervical discectomy and fusion (ACDF) model: a proof-of-concept study.

Objective: The effect of monetite synthetic bone graft (SBG) containing calcium pyrophosphate and β-tricalcium phosphate on cervical spinal fusion in a noninstrumented two-level large animal model.

Summary Of Background Data: ACDF is the gold standard surgical technique for the treatment of degenerative cervical spinal diseases.

Bone formation beyond the skeletal envelope using calcium phosphate granules packed into a collagen pouch-a pilot study.

In this proof-of-concept, bone neoformation beyond the skeletal envelope is explored by using a collagen pouch (= 6) packed with calcium phosphate (CaP) granules placed over the frontal bone in sheep (= 3). At 13 weeks, macroscopic examination showed specimens covered by an adherent fibrinous envelope with slight vascularization. Histology revealed colonization of the implant by newly formed woven bone and fibrous connective tissue.

Nuclear Magnetic Resonance and Metadynamics Simulations Reveal the Atomistic Binding of l-Serine and -Phospho-l-Serine at Disordered Calcium Phosphate Surfaces of Biocements.

Interactions between biomolecules and structurally disordered calcium phosphate (CaP) surfaces are crucial for the regulation of bone mineralization by noncollagenous proteins, the organization of complexes of casein and amorphous calcium phosphate (ACP) in milk, as well as for structure-function relationships of hybrid organic/inorganic interfaces in biomaterials. By a combination of advanced solid-state NMR experiments and metadynamics simulations, we examine the detailed binding of -phospho-l-serine (Pser) and l-serine (Ser) with ACP in bone-adhesive CaP cements, whose capacity of gluing fractured bone together stems from the close integration of the organic molecules with ACP over a subnanometer scale. The proximity of each carboxy, aliphatic, and amino group of Pser/Ser to the Ca and phosphate species of ACP observed from the metadynamics-derived models agreed well with results from heteronuclear solid-state NMR experiments that are sensitive to the C-P and N-P distances.

Bioactive Silicon Nitride Implant Surfaces with Maintained Antibacterial Properties.

Silicon nitride (SiN) is a promising biomaterial, currently used in spinal fusion implants. Such implants should result in high vertebral union rates without major complications. However, pseudarthrosis remains an important complication that could lead to a need for implant replacement.

Pan-cancer analysis of genomic and transcriptomic data reveals the prognostic relevance of human proteasome genes in different cancer types.

Background: The human proteasome gene family (PSM) consists of 49 genes that play a crucial role in cancer proteostasis. However, little is known about the effect of PSM gene expression and genetic alterations on clinical outcome in different cancer forms.

Methods: Here, we performed a comprehensive pan-cancer analysis of genetic alterations in PSM genes and the subsequent prognostic value of PSM expression using data from The Cancer Genome Atlas (TCGA) containing over 10,000 samples representing up to 33 different cancer types.

A new bone adhesive candidate- does it work in human bone? An ex-vivo preclinical evaluation in fresh human osteoporotic femoral head bone.

Introduction: The fixation of small intraarticular bone fragments is clinically challenging and an obvious first orthopaedic indication for an effective bone adhesive. In the present study the feasibility of bonding freshly harvested human trabecular bone with OsStic, a novel phosphoserine modified cement, was evaluated using a bone cylinder model pull-out test and compared with a commercial fibrin tissue adhesive.

Methods: Femoral heads (n=13) were collected from hip fracture patients undergoing arthroplasty and stored refrigerated overnight in saline medium prior to testing.

Cytocompatibility and Bioactive Ion Release Profiles of Phosphoserine Bone Adhesive: Bridge from In Vitro to In Vivo.

One major challenge when developing new biomaterials is translating in vitro testing to in vivo models. We have recently shown that a single formulation of a bone tissue adhesive, phosphoserine modified cement (PMC), is safe and resorbable in vivo. Herein, we screened many new adhesive formulations, for cytocompatibility and bioactive ion release, with three cell lines: MDPC23 odontoblasts, MC3T3 preosteoblasts, and L929 fibroblasts.

Bone without borders - Monetite-based calcium phosphate guides bone formation beyond the skeletal envelope.

Calcium phosphates (CaP) represent an important class of osteoconductive and osteoinductive biomaterials. As proof-of-concept, we show how a multi-component CaP formulation (monetite, beta-tricalcium phosphate, and calcium pyrophosphate) guides osteogenesis beyond the physiological envelope. In a sheep model, hollow dome-shaped constructs were placed directly over the occipital bone.

The Influence of Residuals Combining Temperature and Reaction Time on Calcium Phosphate Transformation in a Precipitation Process.

Precipitation is one of the most common processes to synthesize hydroxyapatite, which is the human body's mineral forming bone and teeth, and the golden bioceramic material for bone repair. Generally, the washing step is important in the precipitation method to remove the residuals in solution and to stabilize the phase transformation. However, the influence of residuals in combination with the reaction temperature and time, on calcium phosphate formation, is not well studied.

Guiding bone formation using semi-onlay calcium phosphate implants in an ovine calvarial model.

The restoration of cranio-maxillofacial deformities often requires complex reconstructive surgery in a challenging anatomical region, with abnormal soft tissue structures and bony deficits. In this proof-of-concept, the possibility of vertical bone augmentation was explored by suspending hemispherically shaped titanium-reinforced porous calcium phosphate (CaP) implants (n = 12) over the frontal bone in a sheep model (n = 6). The animals were euthanized after week 13 and the specimens were subject to micro-computed tomography (μCT) and comprehensive histological analysis.

Experimental Characterization and Mathematical Modeling of the Adsorption of Proteins and Cells on Biomimetic Hydroxyapatite.

Biomaterial development is a long process consisting of multiple stages of design and evaluation within the context of both and testing. To streamline this process, mathematical and computational modeling displays potential as a tool for rapid biomaterial characterization, enabling the prediction of optimal physicochemical parameters. In this work, a Langmuir isotherm-based model was used to describe protein and cell adhesion on a biomimetic hydroxyapatite surface, both independently and in a one-way coupled system.

Monocytes and pyrophosphate promote mesenchymal stem cell viability and early osteogenic differentiation.

Pyrophosphate-containing calcium phosphate implants promote osteoinduction and bone regeneration. The role of pyrophosphate for inflammatory cell-mesenchymal stem cell (MSC) cross-talk during osteogenesis is not known. In the present work, the effects of lipopolysaccharide (LPS) and pyrophosphate (PPi) on primary human monocytes and on osteogenic gene expression in human adipose-derived MSCs were evaluated in vitro, using conditioned media transfer as well as direct effect systems.

Entrapment of a Cytotoxic Drug into the Crystal Structure of Calcite for Targeted Drug Delivery.

Controlled drug release and targeted drug delivery can reduce systemic toxicity of chemotherapeutics by restricting drugs to the target organ and increasing the local concentration. As tumors and inflamed tissue are often surrounded by an acidic microenvironment, pH-responsive calcium carbonates (CaCO) are promising vehicles for controlled drug delivery applications. The aim of this study was to evaluate the loading efficacy and release of a chemotherapeutic drug, Hydroxyurea (HU), into the crystal structure of calcite.

Gluing Living Bone Using a Biomimetic Bioadhesive: From Initial Cut to Final Healing.

Osteoporotic fractures are a growing issue due to the increasing incidence of osteoporosis worldwide. High reoperation rates in osteoporotic fractures call for investigation into new methods in improving fixation of osteoporotic bones. In the present study, the strength of a recently developed bone bioadhesive, OsStic, was evaluated using a novel bone core assay in a murine animal model at 0, 3, 7, 14, 28, and 42 days.

Silk fibroin hydrogels induced and reinforced by acidic calcium phosphate - A simple way of producing bioactive and drug-loadable composites for biomedical applications.

Silk fibroin (SF) hydrogels have attracted extensive interest in biomedical applications due to their biocompatibility and wide availability. However, their generally poor mechanical properties limit their utility. Here, injectable, ready-to-use SF-based composites, simultaneously induced and reinforced by acidic calcium phosphates, were prepared via a dual-paste system requiring no complex chemical/physical treatment.

The use of heat to deliver fentanyl via pulmonary drug delivery.

The golden standard to treat acute pain is by intravenous drug delivery of opioids such as fentanyl or morphine. Intravenous drug delivery requires the placement of an intravenous (IV) port, which can cause infections, dislodgments, and distress to the patients, and therefore a non-invasive method is desirable. Pulmonary drug delivery is a non-invasive method that has been shown to be a good alternative to intravenous administration.

Three-Dimensional Insights into Interfacial Segregation at the Atomic Scale in a Nanocrystalline Glass-Ceramic.

The distribution of dopant atoms plays a key role in the effectiveness of doping, thereby requiring delicate characterizations. In this study, we found that energy-dispersive X-ray spectroscopy (EDX) and electron energy loss spectroscopy (EELS) techniques in scanning transmission electron microscopy (STEM) were not adequate to reveal the distribution of yttrium and the chemical composition of the ZrO/SiO heterophase interface in an yttrium-doped ZrO-SiO nanocrystalline glass-ceramic. Atom probe tomography (APT) is rarely utilized to characterize ceramics due to some inherent difficulties.

Comparative Study of Technologies for Tubule Occlusion and Treatment of Dentin Hypersensitivity.

This study aimed to evaluate the occluding/remineralization performance and resistance to acid attacks of the mineralization layer formed by a tooth-desensitizing gel containing amorphous calcium magnesium phosphate (ACMP) particles and compare it to six other desensitizing products available on the market. Similar comprehensive studies are few and there is especially a lack of studies that are up to date. A dentin-disc model was used for in vitro evaluation of the desensitizing toothpastes/gels.

Monetite-based composite cranial implants demonstrate long-term clinical volumetric balance by concomitant bone formation and degradation.

The use of calcium phosphates (CaPs) as synthetic bone substitutes should ideally result in a volumetric balance with concomitant bone formation and degradation. Clinical data on such properties is nevertheless lacking, especially for monetite-based CaPs. However, a monetite-based composite implant has recently shown promising cranial reconstructions, with both CaP degradation and bone formation.

Amorphous Calcium Magnesium Phosphate Particles for Treatment of Dentin Hypersensitivity: A Mode of Action Study.

Occlusion of exposed dentin tubules may eliminate or reduce dentin hypersensitivity by hindering fluid movements within the tubules. In this study, the mode of action of spherical particles of amorphous calcium magnesium phosphate (180-440 nm in diameter) was studied. A degradation study of the particles in Tris-HCl buffer showed that the particles continuously released Ca, Mg, and phosphate, and XRD analysis revealed the formation of hydroxyapatite (HA) after 1 week.

A biomimetic engineered bone platform for advanced testing of prosthetic implants.

Existing methods for testing prosthetic implants suffer from critical limitations, creating an urgent need for new strategies that facilitate research and development of implants with enhanced osseointegration potential. Herein, we describe a novel, biomimetic, human bone platform for advanced testing of implants in vitro, and demonstrate the scientific validity and predictive value of this approach using an assortment of complementary evaluation methods. We anchored titanium (Ti) and stainless steel (SS) implants into biomimetic scaffolds, seeded with human induced mesenchymal stem cells, to recapitulate the osseointegration process in vitro.

Titanium reinforced calcium phosphate improves bone formation and osteointegration in ovine calvaria defects: a comparative 52 weeks study.

In a 52 week ovine calvaria implantation model, the restoration of cranial defects with a bare titanium mesh (Ti-mesh) and a titanium mesh embedded in a calcium phosphate (CaP-Ti) were evaluated in seven animals. During the study, no major clinical abnormalities were observed, and all sheep presented a normal neurologic assessment. Blood and cerebrospinal fluid analysis, made at termination, did not show any abnormalities.

In situ bone regeneration of large cranial defects using synthetic ceramic implants with a tailored composition and design.

The repair of large cranial defects with bone is a major clinical challenge that necessitates novel materials and engineering solutions. Three-dimensionally (3D) printed bioceramic (BioCer) implants consisting of additively manufactured titanium frames enveloped with CaP BioCer or titanium control implants with similar designs were implanted in the ovine skull and at s.c.

An International Continence Society (ICS) report on the terminology for single-use body worn absorbent incontinence products.

Aims: In 2016, the International Continence Society (ICS) Standardization Steering Committee appointed a working group to address the confusing plethora of synonyms currently used to describe single-use body worn absorbent incontinence products by recommending preferred terminology.

Methods: An online questionnaire was posted in 2016/17 inviting input from stakeholders internationally. The data were analyzed and conclusions progressively refined through working group discussions, an open meeting at the 2017 annual ICS conference, and a review of further iterations-including from the parent ICS Standardization Committee-until consensus was reached.

Integrative genomics approach identifies molecular features associated with early-stage ovarian carcinoma histotypes.

Ovarian cancer comprises multiple subtypes (clear-cell (CCC), endometrioid (EC), high-grade serous (HGSC), low-grade serous (LGSC), and mucinous carcinomas (MC)) with differing molecular and clinical behavior. However, robust histotype-specific biomarkers for clinical use have yet to be identified. Here, we utilized a multi-omics approach to identify novel histotype-specific genetic markers associated with ovarian carcinoma histotypes (CCC, EC, HGSC, and MC) using DNA methylation, DNA copy number alteration and RNA sequencing data for 96 primary invasive early-stage (stage I and II) ovarian carcinomas.