Injectable collagen/α-tricalcium phosphate cement: collagen–mineral phase interactions and cell response

A bone inspired material was obtained by incorporating collagen in the liquid phase of an α-tricalcium phosphate cement, either in solubilized or in fibrilized form. This material was able to set in situ, giving rise to a calcium deficient hydroxyapatite (CDHA)/collagen composite. The morphology and distribution of collagen in the composite was shown to be strongly affected by the collagen pre-treatment. The interactions between collagen and the inorganic phase were assessed by FTIR. A red shift of the amide I band was indicative of calcium chelation by the collagen carbonyl groups. The rate of CDHA formation was not affected when diluted collagen solutions (1 mg/ml) were used, whereas injectability improved. The presence of solubilized collagen, even in low amount (1 %), increased cell adhesion and proliferation on the composites. Still in the absence of osteogenic medium, significant ALP activity was detected both in the inorganic and the collagen-containing cements. The maximum ALP activity was advanced in the collagen-containing cement as compared to the inorganic cement.     

Production and characterization of new calcium phosphate bone cements in the CaHPOv4–α-Ca3(PO4)2 system: pH, workability and setting times

The initial setting properties of calcium phosphate cements in the CaHPOv₄–-Ca₃(PO₄)₂ (DCP–-TCP) system have been investigated. Interest was focused on the pH, workability, cohesion time and initial and final setting times. The addition of CaCO₃ modified the structure of the cement reaction product such that it became more similar to the apatite phase in bone mineral. The addition of 10% w/w of CaCO₃ reduced the viscosity of the cement pastes resulting in an increase in initial and final setting times and improved injectability. © 1999 Kluwer Academic Publishers     

Comparison of a low molecular weight and a macromolecular surfactant as foaming agents for injectable self setting hydroxyapatite foams: Polysorbate 80 versus gelatine

Hydroxyapatite foams are potential synthetic bone grafting materials or scaffolds for bone tissue engineering. A novel method to obtain injectable hydroxyapatite foams consists in foaming the liquid phase of a calcium phosphate cement. In this process, the cement powder is incorporated into a liquid foam, which acts as a template for macroporosity. After setting, the cement hardens maintaining the macroporous structure of the foam. In this study a low molecular weight surfactant, Polysorbate 80, and a protein, gelatine, were compared as foaming agents of a calcium phosphate cement. The foamability of Polysorbate 80 was greater than that of gelatine, resulting in higher macroporosity in the set hydroxyapatite foam and higher macropore interconnectivity. Gelatine produced less interconnected foams, especially at high concentrations, due to a higher liquid foam stability. However it increased the injectability and cohesion of the foamed paste, and enhanced osteoblastic-like cell adhesion, all of them important properties for bone grafting materials.     

Simulation-based designs for multiperiod control

In multiperiod control one sequentially chooses the value of an input variable to keep an output variable close to a target value. At any stage the input variable has to be such that the output is close to target while at the same time it provides as much information as possible about the model that relates input and output, to help keep the output close to target in the future. Certainty equivalence policies set the input variable at the value under which the output is estimated to be equal to target. Three alternative approaches that improve on certainty equivalence by searching for the best policy among families of policies that embed them are proposed, and their use is exemplified both on static as well as on time-varying dynamic models. Two approaches observe on credible regions for the root, while the third one is an adaptation of stochastic approximation sequences.     

Mechanical properties of a modified acrylic bone cement with etoxytriethyleneglycol monomethacrylate

With the aim of improving some of the disadvantages of the acrylic bone cements, an acrylic bone cement based on polymethyl methacrylate has been modified by substituting different quantities, up to 20%, of the monomer methyl methacrylate (MMA) with the same amount of ethoxytriethyleneglycol monomethacrylate (TEG). The addition of this new monomer decreased noticeably the maximum temperature and increased both setting and working times. Mechanical testing revealed that the introduction of TEG gave rise to a less fragile bone cement by increasing slightly the total deformation without any change in the rest of the tensile parameters.     

Biodegradable and semi-biodegradable composite hydrogels as bone substitutes: morphology and mechanical characterization

Biodegradable and semi-biodegradable composite hydrogels are proposed as bone substitutes. They consist of an hydrophilic biodegradable polymer (HYAFF 11) as matrix and two ceramic powders (α-TCP and HA) as reinforcement. Both components of these composites have been of great interest in biomedical applications due to their excellent biocompatibility and tissue interactions, however they have never been investigated as bone substitute composites. Morphological and mechanical analysis have shown that the two fillers behave in a very different way. In the HYAFF 11/α-TCP composite, α-TCP is able to hydrolyze in contact with water while in the HYAFF 11 matrix. As a result, the composite sets and hardens, and entangled CDHA crystals are formed in the hydrogel phase and increases in the mechanical properties are obtained. In the HYAFF11/HA composite the ceramic reinforcement acts as inert phase leading to lower mechanical properties. Both mechanical properties and microstructure analysis have demonstrated the possibility to design hydrophilic biodegradable composite structures for bone tissue substitution applications.     

The effects of temperature on the behaviour of an apatitic calcium phosphate cement

An apatitic calcium phosphate cement is obtained by mixing -tricalcium phosphate (-TCP) and precipitated hydroxyapatite into a cement powder, and by then mixing this powder with an aqueous solution of Na₂HPO₄ as an accelerator. Setting times were reduced by about 30% by increasing the temperature from 22 to 37°C. Compressive strength reached higher intermediate and final values at 37 °C. Degrees of transformation of the -TCP in the resulting calcium-deficient hydroxyapatite (CDHA) were much higher at 37 °C after 24 h of storage in Ringer's solution according to X-ray diffraction. Differential scanning calorimetry indicated that the rate of reaction increased by a factor of about 5 when the temperature was increased from 25 to 37 °C. Scanning electron microscopy showed that the microstructure was more homogeneous and that a more tight entanglement of the precipitated CDHA crystals occurred after storage at 37 °C than at room temperature.     

Acrylic-phosphate glasses composites as self-curing controlled delivery systems of antibiotics

New antibiotic delivery systems based on self-hardening methyl methacrylate (MMA)/polymethyl methacrylate (PMMA) systems and phosphate glasses (PG) in the system P₂O₅–CaO–Na₂O have been developed. Self-curing formulations were prepared by mixing the solid component containing PMMA beads, different proportions of PG (30–70 wt %) and vancomycin (5 wt %) as antibiotic, with the liquid component made of MMA monomer. Dough and setting times increased with the content of PG but peak temperature decreased to values well below to guarantee the chemical stability of the antibiotic drug, gentamicin or vancomycin. Mechanical properties of the PMMA/PG composites were evaluated in compression test giving rise to values of compressive strength in the range of 100 MPa. The release of vancomycin was analyzed in vitro by immersion of samples in phosphate buffer of pH=7.4. Release profiles were influenced by the content of PG present in the cement. An initial burst of drug release was observed in all cases. The composites with 70 wt % PG released nearly the total amount of drug loaded in a period of 45 days, and those containing 60 wt % PG released the 70% of the vancomycin in the same period of time. However, either the control of the composite with 30 wt % PG released only the 30% of the drug in 10–15 days. The surface of the drug-loaded composites before and after release experiments was analyzed by ESEM. The deposition of some aggregates at certain points of the surface was detected for the specimens immersed in buffer phosphate after 45 days. This material was characterized by FTIR and Raman spectroscopy as an amorphous phosphate formed by calcium ortho and pyrophosphates, and indicates an interaction between the hydrated layer at the place of the glass and the surrounding medium.     

Acrylic bone cements incorporating polymeric active components derived from salicylic acid: curing parameters and properties

A methacrylic monomer derived from salicylic acid, 5-hydroxy-2-methacrylamido benzoic acid, 5-HMA, was incorporated with 2-hydroxyethyl methacrylate, (HEMA), in different proportions to the liquid phase of classical bone cement formulations. The monomer 5-HMA shows the ability to form molecular complexes with calcium atoms in order to improve osteointegration in the application of bone cement formulations used for the fixation of joint prostheses such as knee and hip. Kinetic parameters, peak temperature and setting time of the bone cement formulations prepared were determined, obtaining lower peak temperature values when 5-HMA was incorporated, with respect to classical acrylic bone cements based on PMMA. Mechanical and thermal properties as well as surface energy values, have been determined for all cured bone cement formulations. © 1998 Kluwer Academic Publishers     

Two-level experiments for binary response data

Information in a statistical experiment is often measured through the determinant of its information matrix. Under first order normal linear models, the determinant of the information matrix of a two-level factorial experiment neither depends on where the experiment is centered, nor on how it is oriented, and balanced allocations are more informative than unbalanced ones with the same number of runs. In contrast, under binary response models, none of these properties hold. The performance of two-level experiments for binomial responses is explored by investigating the dependence of the determinant of their information matrix on their location, orientation, range, presence or absence of interactions and on the relative allocation of runs to support points, and in particular, on the type of fractionating involved. Conventional wisdom about two-level factorial experiments, which is deeply rooted on normal response models, does not apply to binomial models. In binary response settings, factorial experiments should not be used for screening or as building blocks for binary response surface exploration, and there is no alternative to the optimal design theory approach to planning experiments.