V. S. Komlev

A method to fabricate porous spherical hydroxyapatite granules intended for time-controlled drug release

This study is aimed at the development of a method to fabricate porous spherical hydroxyapatite (HA) granules, which can be impregnated with a drug. These drug-loaded particles can be used as a system for targeted and time-controlled drug delivery, e.g. in bone surgery. The method to produce porous granules is based on liquids immiscibility effect. A suspension of HA powder in aqueous solution of gelatin and oil as a dispersion media were used. By stirring the mixtures of these immiscible liquids, granules of 50 2,000 microm diameter can easily be produced. Dependence of the granules characteristics on the preparation route was studied. In vivo experiments were performed to simulate drug release kinetics from the granules to the blood of rats.

Hydroxyapatite and Hydroxyapatite-Based Ceramics

Data are summarized on the synthesis of hydroxyapatite (HA) by wet-chemical processes, solid-state reactions, and hydrothermal treatment. The conditions for HA preparation via precipitation from solutions of calcium chloride, dibasic ammonium phosphate, and aqueous ammonia are discussed at length. Detailed analysis of the fabrication and properties of calcium-phosphate-based ceramics is presented. The techniques for producing dense and porous HA ceramics are considered. The fabrication and medical applications of HA granules are discussed. Data are presented on HA-based composites.

Micro-CT studies on 3-D bioactive glass–ceramic scaffolds for bone regeneration

The aim of this study was the preparation and characterization of bioactive glass-ceramic scaffolds for bone tissue engineering. For this purpose, a glass belonging to the system SiO2-P2O5-CaO-MgO-Na2O-K2O (CEL2) was used. The sponge-replication method was adopted to prepare the scaffolds; specifically, a polymeric skeleton was impregnated with a slurry containing CEL2 powder, polyvinyl alcohol (PVA) as a binding agent and distilled water. The impregnated sponge was then thermally treated to remove the polymeric phase and to sinter the inorganic one. The obtained scaffolds possessed an open and interconnected porosity, analogous to cancellous bone texture, and with a mechanical strength above 2 MPa. Moreover, the scaffolds underwent partial bioresorption due to ion-leaching phenomena. This feature was investigated by X-ray computed microcomputed tomography (micro-CT). Micro-CT is a three-dimensional (3-D) radiographic imaging technique, able to achieve a spatial resolution close to 1 microm(3). The use of synchrotron radiation allows the selected photon energy to be tuned to optimize the contrast among the different phases in the investigated samples. The 3-D scaffolds were soaked in a simulated body fluid (SBF) to study the formation of hydroxyapatite microcrystals on the scaffold struts and on the internal pore walls. The 3-D scaffolds were also soaked in a buffer solution (Tris-HCl) for different times to assess the scaffold bioresorption according to the ISO standard. A gradual resorption of the pores walls was observed during the soakings both in SBF and in Tris-HCl.

Micromechanics of bone tissue-engineering scaffolds, based on resolution error-cleared computer tomography.

Synchrotron radiation micro-computed tomography (SRmuCT) revealed the microstructure of a CEL2 glass-ceramic scaffold with macropores of several hundred microns characteristic length, in terms of the voxel-by-voxel 3D distribution of the attenuation coefficients throughout the scanned space. The probability density function of all attenuation coefficients related to the macroporous space inside the scaffold gives access to the tomograph-specific machine error included in the SRmuCT measurements (also referred to as instrumental resolution function). After Lorentz function-based clearing of the measured CT data from the systematic resolution error, the voxel-specific attenuation information of the voxels representing the solid skeleton is translated into the composition of the material inside one voxel, in terms of the nanoporosity embedded in a dense CEL2 glass-ceramic matrix. Based on voxel-invariant elastic properties of dense CEL2 glass-ceramic, continuum micromechanics allows for translation of the voxel-specific nanoporosity into voxel-specific elastic properties. They serve as input for Finite Element analyses of the scaffold structure. Youngs modulus of a specific CT-scanned macroporous scaffold sample, predicted from a Finite Element simulation of a uniaxial compression test, agrees well with the experimental value obtained from an ultrasonic test on the same sample. This highlights the satisfactory predictive capabilities of the presented approach.

Calcium phosphate bone cements

The principles of developing calcium phosphate cements (CPCs) for replacement and regeneration of bone tissue are considered. The basic classification of CPCs is given according to the phase composition of the reaction products in the setting systems. Processes of phase composition and development of microstructure and properties are discussed. Injectable CPC compositions are considered, and the factors affecting the injectability, as well as the ways to modify the cement pastes to improve their properties, are discussed. The results of research and development in the field of composite CPCs, including those reinforced by disperse phases, are described. In the final part of the review, some data on commercial CPCs and their biological behavior are presented.

Porous spherical hydroxyapatite and fluorhydroxyapatite granules: processing and characterization

Abstract This study is aimed at the development of a method to fabricate porous spherical hydroxyapatite (HA)—fluorapatite (FA) granules. The method to produce porous granules is based on liquid immiscibility effect. A suspension of HA–FA powder mixtures in aqueous solution of gelatin and oil as a dispersion media were used. By stirring the mixtures of these immiscible liquids, granules of 50—200 mm diameter can easily be produced. The granules were characterized with respect to their microstructure, phase composition and specific area. In vitro testing of human plasma protein adsorption onto the granules of HA and fluorhydroxyapatite were performed. No kind of difference in the dynamic protein adsorption between pure HA and the HA up to 10 wt% FA materials has been revealed.

X-Ray Synchrotron Radiation Pseudo-Holotomography as a New Imaging Technique to Investigate Angio- and Microvasculogenesis with No Usage of Contrast Agents

Standard X-ray micro-computed tomography is a technique that allows a good visualization of the structure of mineralized tissues and biomaterials, but it fails to finely discern soft tissues. Here, we used X-ray synchrotron radiation pseudo-holotomography to visualize, at three-dimensional (3D) level, microvascular networks for the first time with no need for contrast agents, and to extract quantitative structural data in a bone-engineered construct implanted for 24 weeks in a mouse. When compared to standard histology, pseudo-holotomography allowed a previously unavailable 3D resolution of the vessels, which in turn appeared more clearly visible. Thus, pseudo-holotomography is an innovative technique that offers a promising powerful tool to investigate angio- and microvasculogenesis in advanced biomedical research areas such as regenerative medicine and antiangiogenic cancer therapies.

High-resolution X-ray microtomography for three-dimensional visualization of human stem cell muscle homing

In the perspective of clinical translation of stem cell research, it would be advantageous to develop new techniques to detect donor cells after transplantation to track their fate and thus better understand their role in regeneration of damaged and diseased tissues. In this study we use X‐ray computed microtomography for three‐dimensional visualization of stem cells that were labeled with magnetic nanoparticles and transplanted via intra‐arterial infusion. We show that X‐ray computed microtomography offers the possibility to detect with high definition and resolution human cells after transplantation, and opens new possibilities for both experimental stem cell research.

Bioceramics composed of octacalcium phosphate demonstrate enhanced biological behavior.

Bioceramics are used to treat bone defects but in general do not induce formation of new bone, which is essential for regeneration process. Many aspects related to bioceramics synthesis, properties and biological response that are still unknown and, there is a great need for further development. In the most recent research efforts were aimed on creation of materials from biological precursors of apatite formation in humans. One possible precursor is octacalcium phosphate (OCP), which is believed to not only exhibit osteoconductivity but possess osteoinductive quality, the ability to induce bone formation. Here we propose a relatively simple route for OCP ceramics preparation with a specifically designed microstructure. Comprehensive study for OCP ceramics including biodegradation, osteogenic properties in ortopic and heterotopic models and limited clinical trials were performed that demonstrated enhanced biological behavior. Our results provide a possible new concept for the clinical applications of OCP ceramics.

Osteoinductive ceramic materials for bone tissue restoration: Octacalcium phosphate (review)

Data are presented on the structure and properties of octacalcium phosphate, which exhibits osteoinductivity, i.e., the ability to stimulate bone tissue formation in living organisms. Some features of its chemical synthesis by precipitation from aqueous solutions or by hydrolysis of other calcium phosphates are described. The results of studies of the transformations that take place in octacalcium phosphate in simulated body fluid, as well as data of biological tests on animals in vivo, are given.