Novel anti-decay self-setting paste of hydroxyapatite/collagen nanocomposite utilizing GPTMS

Bone is a typical inorganic/ortganic nanocomposite mainly composed of hydroxyapatite (HAp) nanocrystals and collagen molecules. The composition and nanostructure is closely related to bone’s biomechanical and biochemical properties. One of the most important things for bone is a bone remodeling process that maintains mechanical strength of bone to allow walking and running as well as homeostasis of calcium in our body. In fact, sintered HAp composed of HAp crystals approximately 1 µm in particle size is considered as non-bioresorbable; however HAp nanocrystals easily resorbed by osteoclasts. A hydroxyapatite/collagen bone-like nanocomposite (HAp/Col) was successfully synthesized by the authors via self-organizing process. [1] The HAp/Col is incorporated into bone remodeling process completely as the same as the autologous bone transplanted and substituted with new bone in 3 months. Porous type HAp/Col was also developed by the authors and shows spoge-like viscoelastity in wet condition. [2] The porous HAp/Col had been tested clinically and has been being sold in Japan from April, 2013 as ReFit®. According to the clinical test [3], the HAp/Col shows higher rate of remarkable efficiency in comparison to Osferion®, porous β-tricalcium phosphate, for substitution with newly formed bone. In addition, sponge-like deformability allows to fit irregular shape of bone defects as well as to press to pack the porous HAp/Col in cavity created by removal of benign bone tumor. On the other hand, recent need from surgeon for bone filler is a self-setting bone paste with bioresorbability. Previously, the HAp/Col anti-decay self-setting paste was prepared successfully with the use of sodium alginate and calcium compounds. It showed tolerant paste properties; however, the paste contained 30 % in mass of calcium compounds that could interfered excellent biological activity of the HAp/Col. In this study, the HAp/Col paste with injectability, self-setting and anti-decay abilities was prepared using the HAp/Col powder and 1 % in volume of 3-glycidoxypropyl)methyldiethoxysilane (GPTMS) aqueous solution. The paste obtained was evaluated by viscosity, hardening behavior and anti-decay property tests. The HAp/Col was synthesized according to ref 1. The HAp/Col was compacted with specially designed mold by uniaxially press squeezing of water from the HAp/Col. The HAp/Col compact was then crushed and ball-milled to obtain the HAp/Col particles of 100 µm or less in size. The GPTMS was dissolved in pure water at 1 % in volume and steadily placed in 25 °C for 1 h to allow hydrolysis of the GPTMS to form silanol groups. The HAp/Col powder (powder phase, P) and the GPTMS aqueous solution (liquid phase, L) were mixed at 0.20-2.00 of P/L ratio in g/cm3 to obtain a HAp/Col paste. A viscosity of the HAp/Col paste obtained was measured according to ref 1. Briefly, the paste obtained was shaped to cylinder at 5 mm in diameter and 5.1 mm in hight and start pressing at 10 min after mixing by 2 kg weight for 10 min. A spread area of the paste was measured from digital photo with Image-J. Hardening behavior was measured using the viscosity test as a function of time, because softness of the paste did not allow to apply conventional the needle method. Anti-decay property was tested according to JIS T 0330-4:2012 [5]; briefly, the paste shaped in cylinder 4.8 mm in diameter and 16.5 mm in height was placed on wire mesh and, at 5 min after mixing, soaked in phosphate buffered saline for 72 h. Debris were then collected and measured their mass, and decay ratio was calculated as debris/original masses. The paste with P/L ratio of 0.2 could not shaped by its high fluidity and that of 2.0 could not shaped because of its aggregation. The paste with P/L ratio of 0.33 could injected through 18G needle and others could injected through syringe with 1.8 mm in inner diameter. The viscosity of the paste increased with increasing in P/L ratio and did not depend on the amounts of GPTMS. The initial hardening was observed first 30-40 min from mixing and gradually hardened. The paste with P/L ratio of 1.5 showed mechanical strength more than 1 MPa with viscoelastic property. No significant decay was observed for all pastes. The HAp/Col-GPTMS paste can be good candidate for high performance injectable bone filler as well as a raw material for 3D printing

Helicobacter pylori Exploits Host Membrane Phosphatidylserine for Delivery, Localization, and Pathophysiological Action of the CagA Oncoprotein

SummaryWhen delivered into gastric epithelial cells via type IV secretion, Helicobacter pylori CagA perturbs host cell signaling and thereby promotes gastric carcinogenesis. However, the mechanisms of CagA delivery, localization, and action remain poorly understood. We show that direct contact of H. pylori with epithelial cells induces externalization of the inner leaflet enriched host phospholipid, phosphatidylserine, to the outer leaflet of the host plasma membrane. CagA, which is exposed on the bacterial surface via type IV secretion, interacts with the externalized phosphatidylserine to initiate its entry into cells. CagA delivery also requires energy-dependent host cell processes distinct from known endocytic pathways. Within polarized epithelial cells, CagA is tethered to the inner leaflet of the plasma membrane through interaction with phosphatidylserine and binds the polarity-regulating host kinase PAR1/MARK to induce junctional and polarity defects. Thus, host membrane phosphatidylserine plays a key role in the delivery, localization, and pathophysiological action of CagA

Crack growth simulation in heterogeneous material by S-FEM and comparison with experiments

Fully automatic fatigue crack growth simulation system is developed using S-version FEM (SFEM).This system is extended to fracture in heterogeneous material. In the heterogeneous material, crack tipstress field becomes mixed mode condition, and crack growth path is affected by inhomogeneous materials and mixed mode conditions. Stress Intensity Factors (SIF) in mixed mode condition are evaluated using VirtualCrack Closure Method (VCCM). Criteria for crack growth amount and crack growth path are used based on these SIFs, and growing crack configurations are obtained.Three crack growth problems are simulated. One is crack growth in bi-materila made of CFRP plate andAluminum alloy. Initial crack is located in CFRP plate, and grows toward Aluminum alloy. Crack growingdirection changes and results are compared with experimental one. Second problem is crack growth in bimaterial made of PMMA and Aluminum alloy. Initial crack is located in PMMA plate and parallel to phaseboundary. By cahnging loading conditions, several cases are simulated and compared with experimental ones.In the experiment, crack grows into phase boundary and grow along it. This case is simulated precisely, and theeffect of pahse boundary is discussed. Last case is Stress Corrosion Cracking (SCC) at Hot-Leg Safe-End ofPressurized Water Rreactor. This location is made of many kinds of steels by welding. In some steel, SCC doesnot occur and in other steel, SCC is accelerated. As a result, small surface crack grows in complicated manner

Fatigue crack growth simulation of two non-coplanar embedded cracks using s-version finite element method

In this paper, the fatigue crack growth simulation of two non-coplanar embedded cracks using the s-version finite element method is presented, and the validity and reliability of the alignment rule for two non-coplanar cracks are evaluated. According to the previous numerical and experimental studies on two non-coplanar surface cracks, the simulated fatigue crack growth behavior is categorized into five patterns to discuss the criteria for the application of the alignment rule. The results suggest that the strength of interaction between the non-coplanar embedded cracks is similar to that between non-coplanar surface cracks. Finally, the interaction of the cracks is evaluated by the stress intensity factor, and the categorization of the fatigue crack growth behavior is discussed by the stress intensity factor. It can be found that the boundary corresponding to the criteria of the application of the alignment rule can be determined as the ratio of the stress intensity factor is 4%. Thus, instead of making a decision of the fatigue crack growth pattern based on the visual inspection, the ratio of the stress intensity factor can be used, and should give more quantitative evaluation of the interaction of two non-coplanar embedded cracks