On the significance of remodeling space and activation rate changes in bone remodeling

This paper quantifies the relative contributions of the remodeling space and the accumulation of Haversian canals to bone porosity at various ages. It also examines the importance of variations in the rate of bone remodeling that occur during growth and aging, and as a result of trauma and disease. The dependence of the remodeling space (cavities due to resorbing, reversing, and refilling BMUs) and the Haversian canal components of porosity on the Basic Multicellular Unit (BMU) activation frequency are mathematically formulated. A graph is developed using data for the cortex of the human rib which shows the extent to which porosity is primarily due to the remodeling space in children, and to accumulated Haversian canals in adults. It is shown that the diminution of activation frequency between birth and age 35 contributes to the concurrent increase in bone volume fraction, and the increase in activation frequency after age 35 contributes to the subsequent decline of bone volume fraction. An equation is derived for determining the time rate of change of activation frequency using two fluorochrome labels.     

红霉素缓释微囊的制备及其释药机理的研究

本文旨在探讨红霉素微囊的制备及体外缓释机理。以明胶等为囊材,用红霉素制成微囊,研究微囊的厚度及孔隙度对药物释放速率的影响。进行理论分析,与实验结果相符性较好。     

Studies on tableting properties of lactose

The consolidation and compaction behaviour of sieve fractions of crystalline -lactose monohydrate were studied. From mercury porosimetry measurements tablet pore surface areas were derived. At a certain compaction load it appeared that tablets compressed from small particles were generally stronger and showed a larger surface area than compacts prepared from coarse sieve fractions. By plotting compact strength against pore surface area, a unique linear relationship was obtained. From these results it can be concluded that the actual tablet surface area, being a function of both the initial particle size and applied compaction pressure, is responsible for the compact strength.     

Effect of volume of porogens on the porosity of PLGA scaffolds in pH-controlled environment

Poly(lactic-co-glycolic acid) (PLGA) is a well-studied biodegradable polymer used in drug delivery and other medical applications such as in tissue regeneration. It is often necessary to impart porosity within the scaffold (microparticles) in order to promote the growth of tissue during the regeneration process. Sodium chloride and ammonium bicarbonate have been extensively used as porogens in the generation of porous microstructure. In this study, we compared the effect of volumes (250?μl, 500?μl and 750?μl) of two porogens, sodium chloride (1.71 M) and ammonium bicarbonate (1.71 M), on the porosity of PLGA microparticles.     

Effect of coating thickness and its material on the stress distribution for dental implants

Dental implants have been increasingly used to recover the masticatory function of lost teeth. It has been well known that the success of a dental implant is heavily dependent on initial stability and long-term osseointegration due to optimal stress distribution in the surrounding bones by the concept implant surface coating. Hydroxyapatite (HAP), as a coating material, has been widely used in dentistry due to its biocompatibility. Some investigations show a benefit of coating dental implants with HAP, and others concluded that HAP coating reduces the long-term implant survival. Therefore, the aim of this investigation is to design a new functionally graded dental implant coating, as well as studying the effect of coating thickness on the maximum von Mises stresses in bone adjacent to the coating layer. The gradation of the elastic modulus is changed along the longitudinal direction. Stress analysis using a finite element method showed that using a coating thickness of 150 µm, functionally graded from titanium at the apex to the collagen at the root, will successfully reduce the maximum von Mises stress in bone by 19% and 17% compared to collagen and HAP coating respectively.     

A mechanism for effective cell-seeding in rigid,microporous substrates

Seeding cells into porous ceramic substrates has been shown to improve outcomes in surgical repair of large bone defects, but the physics underlying cellular ingress into such scaffolds remains elusive. This paper demonstrates capillary forces as a novel, yet simple, self-loading or self-seeding mechanism for rigid, microporous substrates. Capillary forces were found to draw cells through a microporous network with interconnections smaller than the diameter of the cells in suspension. Work here emphasizes CaP-based bone scaffolds containing both macroporosity (>100 μm) and microporosity (5–50 μm); these have been shown to improve bone formation in vivo as compared to their macroporous counterparts and also performed better than microporous scaffolds containing BMP-2 by some measures of bone regeneration. We hypothesize that capillary force driven self-seeding in both macro- and micropores may underlie this improvement, and present a mathematical model and experiments that support this hypothesis. The cell localization and penetration depth within these two-dimensional substrates in vitro depends upon both the cell type (size and stiffness) and the capillary forces generated by the microstructure. Additional experiments showing that cell penetration depth in vitro depends on cell size and stiffness suggest that microporosity could be tailored to optimize cell infiltration in a cell-specific way. Endogenous cells are also drawn into the microporous network in vivo. Results have important implications for design of scaffolds for the healing of large bone defects, and for controlled release of drugs in vivo.     

Enhancing tablet disintegration characteristics of a highly water-soluble high-drug-loading formulation by granulation process

Abstract

The objective of this study was to improve the disintegration and dissolution characteristics of a highly water-soluble tablet matrix by altering the manufacturing process. A high disintegration time along with high dependence of the disintegration time on tablet hardness was observed for a high drug loading (70% w/w) API when formulated using a high-shear wet granulation (HSWG) process. Keeping the formulation composition mostly constant, a fluid-bed granulation (FBG) process was explored as an alternate granulation method using a 2^(4?1) fractional factorial design with two center points. FBG batches (10 batches) were manufactured using varying disingtegrant amount, spray rate, inlet temperature (T) and atomization air pressure. The resultant final blend particle size was affected significantly by spray rate (p?=?.0009), inlet T (p?=?.0062), atomization air pressure (p?=?.0134) and the interaction effect between inlet T*spray rate (p?=?.0241). The compactibility of the final blend was affected significantly by disintegrant amount (p?<?.0001), atomization air pressure (p?=?.0013) and spray rate (p?=?.05). It was observed that the fluid-bed batches gave significantly lower disintegration times than the HSWG batches, and mercury intrusion porosimetry data revealed that this was caused by the higher internal pore structure of tablets manufactured using the FBG batches.     

A novel design of injectable porous hydrogels with in situ pore formation

The use of injectable porous hydrogels is of great interest in biomedical applications due to their excellent permeability and ease of integration into sites of surgical intervention. By implementing a method that enables the formation in situ of pores with controllable porosity and pore size, it is possible to synthesize bioactive hydrogels that are tailor-made for specific biomedical applications. An emulsion-templating technique was used to encapsulate oil droplets, which are subsequently leached out of the hydrogel to create the porous structure. Pore size and porosity were manipulated by changing oil-to-water ratios and the surfactant concentrations. Highly swellable porous hydrogels were obtained with control over mechanical strength and diffusive properties. The relationship between porosity, pore size, and the hydrogel’s physical and mechanical characteristics was analyzed, and the potential of this material as a protein drug delivery system was demonstrated.     

Osseointegration of dental implants in 3D-printed synthetic onlay grafts customized according to bone metabolic activity in recipient site

Onlay grafts made of monolithic microporous monetite bioresorbable bioceramics have the capacity to conduct bone augmentation. However, there is heterogeneity in the graft behaviour in vivo that seems to correlate with the host anatomy. In this study, we sought to investigate the metabolic activity of the regenerated bone in monolithic monetite onlays by using positron emission tomography–computed tomography (PET-CT) in rats. This information was used to optimize the design of monetite onlays with different macroporous architecture that were then fabricated using a 3D-printing technique. In vivo, bone augmentation was attempted with these customized onlays in rabbits. PET-CT findings demonstrated that bone metabolism in the calvarial bone showed higher activity in the inferior and lateral areas of the onlays. Histological observations revealed higher bone volume (up to 47%), less heterogeneity and more implant osseointegration (up to 38%) in the augmented bone with the customized monetite onlays. Our results demonstrated for the first time that it is possible to achieve osseointegration of dental implants in bone augmented with 3D-printed synthetic onlays. It was also observed that designing the macropore geometry according to the bone metabolic activity was a key parameter in increasing the volume of bone augmented within monetite onlays.     

Microstructure and deformation behavior of biocompatible TiO2 nanotubes on titanium substrate

Titanium oxide coatings have been shown to exhibit desirable properties as biocompatible coatings. We report on the quantitative microstructure characterization and deformation behavior of TiO₂ nanotubes on Ti substrate. Nanotubes were processed using anodic oxidation of Ti in a NaF electrolyte solution. Characterization of the as-processed coatings was conducted using scanning electron microscopy and focused ion beam milling. Increases in anodization time had no significant effect on tube diameter or tube wall thickness. Coating thickness, however, increased with time up to 2 h of anodization, at which point an equilibrium thickness was established. Nanoindentation was used to probe the mechanical response in terms of Young’s modulus and hardness. Progressively higher values of elastic modulus were obtained for thinner films consistent with increasing effects of the Ti substrate. A possible deformation mechanism of densification of the porous oxide and wear of the dense surface is suggested and discussed.