Comparison of the effect of locking vs standard screws on the mechanical properties of bone-plate constructs in a comminuted diaphyseal fracture model

The purpose of this study was to compare the mechanical properties of bone-plate constructs with locking compression plates (LCP) used either with standard screws or with locking screws on an experimental model of comminuted fracture

Nanoanalytical Electron Microscopy Reveals a Sequential Mineralization Process Involving Carbonate-Containing Amorphous Precursors

A direct observation and an in-depth characterization of the steps by which bone mineral nucleates and grows in the extracellular matrix during the earliest stages of maturation, using relevant biomineralization models as they grow into mature bone mineral, is an important research goal. To better understand the process of bone mineralization in the extracellular matrix, we used nanoanalytical electron microscopy techniques to examine an in vitro model of bone formation. This study demonstrates the presence of three dominant CaP structures in the mineralizing osteoblast cultures: <80 nm dense granules with a low calcium to phosphate ratio (Ca/P) and crystalline domains; calcium phosphate needles emanating from a focus: “needle-like globules” (100–300 nm in diameter) and mature mineral, both with statistically higher Ca/P compared to that of the dense granules. Many of the submicron granules and globules were interspersed around fibrillar structures containing nitrogen, which are most likely the signature of the organic phase. With high spatial resolution electron energy loss spectroscopy (EELS) mapping, spatially resolved maps were acquired showing the distribution of carbonate within each mineral structure. The carbonate was located in the middle of the granules, which suggested the nucleation of the younger mineral starts with a carbonate-containing precursor and that this precursor may act as seed for growth into larger, submicron-sized, needle-like globules of hydroxyapatite with a different stoichiometry. Application of analytical electron microscopy has important implications in deciphering both how normal bone forms and in understanding pathological mineralization

Cobalt containing glass fibres and their synergistic effect on the HIF-1 pathway for wound healing applications

Introduction and Methods: Chronic wounds are a major healthcare problem, but their healing may be improved by developing biomaterials which can stimulate angiogenesis, e.g. by activating the Hypoxia Inducible Factor (HIF) pathway. Here, novel glass fibres were produced by laser spinning. The hypothesis was that silicate glass fibres that deliver cobalt ions will activate the HIF pathway and promote the expression of angiogenic genes. The glass composition was designed to biodegrade and release ions, but not form a hydroxyapatite layer in body fluid. Results and Discussion: Dissolution studies demonstrated that hydroxyapatite did not form. When keratinocyte cells were exposed to conditioned media from the cobalt-containing glass fibres, significantly higher amounts of HIF-1α and Vascular Endothelial Growth Factor (VEGF) were measured compared to when the cells were exposed to media with equivalent amounts of cobalt chloride. This was attributed to a synergistic effect of the combination of cobalt and other therapeutic ions released from the glass. The effect was also much greater than the sum of HIF-1α and VEGF expression when the cells were cultured with cobalt ions and with dissolution products from the Co-free glass, and was proven to not be due to a rise in pH. The ability of the glass fibres to activate the HIF-1 pathway and promote VEGF expression shows the potential for their use in chronic wound dressings

Multiscale analyses reveal native-like lamellar bone repair and near perfect bone-contact with porous strontium-loaded bioactive glass

The efficient healing of critical-sized bone defects using synthetic biomaterial-based strategies is promising but remains challenging as it requires the development of biomaterials that combine a 3D porous architecture and a robust biological activity. Bioactive glasses (BGs) are attractive candidates as they stimulate a biological response that favors osteogenesis and vascularization, but amorphous 3D porous BGs are difficult to produce because conventional compositions crystallize during processing. Here, we rationally designed a porous, strontium-releasing, bioactive glass-based scaffold (pSrBG) whose composition was tailored to deliver strontium and whose properties were optimized to retain an amorphous phase, induce tissue infiltration and encourage bone formation. The hypothesis was that it would allow the repair of a critical-sized defect in an ovine model with newly-formed bone exhibiting physiological matrix composition and structural architecture. Histological and histomorphometric analyses combined with indentation testing showed pSrBG encouraged near perfect bone-to-material contact and the formation of well-organized lamellar bone. Analysis of bone quality by a combination of Raman spectral imaging, small-angle X-ray scattering, X-ray fluorescence and focused ion beam-scanning electron microscopy demonstrated that the repaired tissue was akin to that of normal, healthy bone, and incorporated small amounts of strontium in the newly formed bone mineral. These data show the potential of pSrBG to induce an efficient repair of critical-sized bone defects and establish the importance of thorough multi-scale characterization in assessing biomaterial outcomes in large animal models

A Critical Tryptophan and Ca2+ in Activation and Catalysis of TPPI, the Enzyme Deficient in Classic Late-Infantile Neuronal Ceroid Lipofuscinosis

Tripeptidyl aminopeptidase I (TPPI) is a crucial lysosomal enzyme that is deficient in the fatal neurodegenerative disorder called classic late-infantile neuronal ceroid lipofuscinosis (LINCL). It is involved in the catabolism of proteins in the lysosomes. Recent X-ray crystallographic studies have provided insights into the structural/functional aspects of TPPI catalysis, and indicated presence of an octahedrally coordinated Ca(2+).Purified precursor and mature TPPI were used to study inhibition by NBS and EDTA using biochemical and immunological approaches. Site-directed mutagenesis with confocal imaging technique identified a critical W residue in TPPI activity, and the processing of precursor into mature enzyme.NBS is a potent inhibitor of the purified TPPI. In mammalian TPPI, W542 is critical for tripeptidyl peptidase activity as well as autocatalysis. Transfection studies have indicated that mutants of the TPPI that harbor residues other than W at position 542 have delayed processing, and are retained in the ER rather than transported to lysosomes. EDTA inhibits the autocatalytic processing of the precursor TPPI.We propose that W542 and Ca(2+) are critical for maintaining the proper tertiary structure of the precursor proprotein as well as the mature TPPI. Additionally, Ca(2+) is necessary for the autocatalytic processing of the precursor protein into the mature TPPI. We have identified NBS as a potent TPPI inhibitor, which led in delineating a critical role for W542 residue. Studies with such compounds will prove valuable in identifying the critical residues in the TPPI catalysis and its structure-function analysis

Nanocellulose/bioactive glass cryogels as scaffolds for bone regeneration

A major challenge exists in the preparation of scaffolds for bone regeneration, namely, achieving simultaneously bioactivity, biocompatibility, mechanical performance and simple manufacturing. Here, cellulose nanofibrils (CNF) are introduced for the preparation of scaffolds taking advantage of their biocompatibility and ability to form strong 3D porous networks from aqueous suspensions. CNF are made bioactive for bone formation through a simple and scalable strategy that achieves highly interconnected 3D networks. The resultant materials optimally combine morphological and mechanical features and facilitate hydroxyapatite formation while releasing essential ions for in vivo bone repair. The porosity and roughness of the scaffolds favor several cell functions while the ions act in the expression of genes associated with cell differentiation. Ion release is found critical to enhance the production of the bone morphogenetic protein 2 (BMP-2) from cells within the fractured area, thus accelerating the in vivo bone repair. Systemic biocompatibility indicates no negative effects on vital organs such as the liver and kidneys. The results pave the way towards a facile preparation of advanced, high performance CNF-based scaffolds for bone tissue engineering

Treatment of femoral and tibial fractures in puppies by elastic plate osteosynthesis

SummarySeventeen puppies, two to four months old, with a femoral (n=12) or tibial (n=5) diaphyseal fracture were treated by elastic plate osteosynthesis with a Veterinary Cuttable Plate (VCP) or straight plate. In one case of femoral fracture treated with a VCP, plate bending due to an excessive elasticity of the implant was observed three days after the osteosynthesis and surgical revision was required. Two cases of femoral overgrowth and one case of slight femoral head and neck retroversion were identified during the radiographic follow-up but without any clinical consequences. Bone healing was obtained for all fractures four to eight weeks (5.64±0.88 weeks) after the surgical procedure, and functional results were excellent in all cases. Our study confirms that elastic plate osteosynthesis with either a VCP or straight plate can be used to treat femoral diaphyseal fractures in medium and large breed puppies less than four months old, but that modification of implant elasticity or rigid osteosynthesis use is required when such puppies reach four months. The same technique can also be used successfully to treat tibial fractures in puppies younger than four months old.</jats:p

Type IV Monteggia fracture in a cat

SummaryA one-year-old neutered male cat was referred for a grade IIIA open radius and ulna fracture. The mid-diaphyseal radial and ulnar fractures were associated with lateral radio-humeral and radio-ulnar dislocations. From these abnormalities, a diagnosis of type IV Monteggia fracture was made. The annular ligament was found to be intact on examination and the radial head was correctly positioned and stable after fracture reduction and plate fixation. Eighteen months postoperatively, the cat did not exhibit any signs of lameness or any signs of pain on palpation and mobilisation. Signs of mild osteoarthritis were present on radiographs.Type IV Monteggia fractures are very rare in animals. The combination of a radial head dislocation with an intact annular ligament is uncommon. This pattern allowed a single reconstruction with two plates without a radio-ulnar screw.</jats:p