Charles Baquey

Cellulose phosphates as biomaterials. In vivo biocompatibility studies.

Femoral implantation of regenerated cellulose hydrogels revealed their biocompatibility, but a complete osseointegration could not be observed. Phosphorylation was therefore envisaged as the means to enhance cellulose bioactivity. In vitro studies showed that regenerated cellulose hydrogels promote bone cells attachment and proliferation but do not mineralize in acellular simulated physiological conditions. On the contrary, phosphorylated cellulose has shown an opposite behavior, by inducing the formation of a calcium phosphate layer in simulated physiological conditions, but behaving as a poor substrate for bone cells attachment and proliferation. In order to investigate the in vivo behavior of these materials, and assess the influence of mineralization induction ability vs. bone cells compatibility, unmodified and phosphorylated cellulose hydrogels were implanted in rabbits for a maximum period of 6 months and bone regeneration was investigated. Despite the difficulties arising from the retraction of cellulose hydrogels upon dehydration during the preparation of retrieved implants, histological observations showed no inflammatory response after implantation, with bone intra-spongious regeneration of cells and the integration of the unmodified as well as the phosphorylated cellulose implants. After a maximum implantation period of 6 months, histological observations, histomorphometry and the measurement of the amount of 45Ca incorporated in the surrounding tissue indicated a slightly better osseointegration of phosphorylated cellulose, although no significant differences between the two materials were found.

Cellulose phosphates as biomaterials. Mineralization of chemically modified regenerated cellulose hydrogels

Femoral implantation of regenerated cellulose hydrogels revealed their biocompatible and osteoconductive properties, but a complete osseointegration could not be observed. Phosphorylation was therefore envisaged as the means to enhance cellulose bioactivity. Once implanted, phosphorylated cellulose could promote the formation of calcium phosphates, having therefore closer resemblance to bone functionality and assuring a satisfactory bonding at the interface between hard tissue and biomaterial. In the present work, regenerated cellulose hydrogels were surface modified via phosphorylation. Phosphorylated materials, having varying degrees of substitution, were soaked in a Simulated Body Fluid (SBF) solution in order to investigate their ability to induce the formation of a calcium phosphate layer. Mineralization was assessed by Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS) and Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy. It was demonstrated that the calcium salt of cellulose phosphates mineralized at a higher extent than materials only phosphorylated. The degree of phosphorylation influenced the extent of surface mineralization. Moderate degrees of surface phosphorylation promoted the highest extent of mineralization. This was attributed to inadequate functionality of the surface in terms of density of PO4 groups and overall surface charge, in the case of low and high phosphate contents.

Experimental Evaluation of a Collagen-coated Vicryl Mesh as a Dural Substitute

Dural substitutes must provide immediate restitution of a membranous covering for the brain without inducing any adverse reaction in the host or provoking adhesions to underlying nervous tissues. Ideally, the material should disappear completely and be replaced by tissues similar to the dura mater. In this study, parietal dural defects were created in 12 beagle dogs and closed with a vicryl mesh prosthesis made watertight by a film of bovine collagen. Clinical and biological tolerances were satisfactory. There was one case of early local infection. Gross and microscopic examinations performed between 7 days and 9 months after implantation showed degradation of the prosthetic mesh and connective tissue growth into the implant mimicking dura mater as early as 15 days after implantation. There was no attendant inflammatory reaction or cortical adhesions or other adverse reactions. The authors conclude that collagen-embedded vicryl mesh provides satisfactory biological function and compatibility when used as a substitute for dura mater in the dog.

Hemocompatibility of titanium nitride.

The left ventricular assist device is based on the principle of the Maillard-Wenkel rotative pump. The materials which make up the pump must present particular mechanical, tribological, thermal and chemical properties. Titanium nitride (TiN) because of its surface properties and graphite because of its bulk characteristics have been chosen. The present study evaluated the in vitro hemocompatibility of TiN coating deposited by the chemical vapor deposition process. Protein adsorption, platelet retention and hemolysis tests have been carried out. In spite of some disparities, the TiN behavior towards albumin and fibrinogen is interesting, compared with the one of a reference medical grade elastomer. The platelet retention test gives similar results as those achieved with the same elastomer. The hemolysis percentage is near to zero. TiN shows interesting characteristics, as far as mechanical and tribological problems are concerned, and presents very encouraging blood tolerability properties.

Study of in vitro and in vivo stability of liposomes loaded with calcitonin or indium in the gastrointestinal tract

Factors affecting liposome transport to the blood compartment after oral administration to rats were evaluated. A high entrapment of calcitonin (CT) was obtained when the vesicles were prepared by sonication and were composed of egg phosphatidylcholine, cholesterol and stearylamine. In vitro tests showed that the liposomes were stable in light acidic or basic buffers, but that they were partly lysed in pH 2.5, 10 mM bile salts and pancreatin. Oral administration of liposomes entrapping calcitonin in fasting rats showed that the vesicles facilitate transport of the hormone to the general circulation and that they increase the lifetime of 125I-CT in blood. Oral administration of liposomes entrapping radioactive indium in fasting rats did not induce radioactivity in blood. This could be explained by disruption of most of the vesicles in the enterocytes.

Mineralization of regenerated cellulose hydrogels.

Due to their high water swelling, regenerated cellulose hydrogels and sponges were pre-incubated in a Ca-containing solution, and their mineralization was investigated. Results obtained demonstrate that a simple pre-incubation treatment in a Ca containing solution can induce mineralization in materials with limited or no tendency to mineralize. The minerals formed had an apatitic carbonated and poorly crystalline structure, resembling carbonated hydroxyapatite found in bone mineral. The apatitic layer formed showed a relatively accelerated growth using this technique, exhibiting nodules in their macroscopic structure, which seem to indicate lateral growth. The porous structure of regenerated cellulose sponges was also homogeneously mineralized using this technique.

Blood haemolysis by ceramics

Ceramics are more and more frequently under consideration for construction of blood-contacting devices, i.e. cardiac valves or cardiac assist devices. This study evaluated the haemolysis eventually initiated in vitro by ceramic powders (Al2O3, ZrO2/Y2O3, AlN, B4C, BN, SiC, Si3 N4, TiB2, TiN, TiC), graphite and diamond. The chemical composition of the powders was studied by X-ray microprobe and various other methods, and BET specific areas were determined. The haemolysis was almost zero for all powders, except AlN which showed slight haemolysis and TiB2 which had high haemolytic power.

Haemocompatibility of Ti6A14V alloy.

Ti6A14V alloy has been mainly used as a biomaterial in the orthopaedic field. The present study describes the surface state of the Ti6A14V material and evaluates its in vitro haemocompatibility in terms of protein adsorption, platelet retention and haemolysis. The behaviour of the Ti6A14V alloy towards albumin and fibrinogen was compared to that of a reference medical-grade elastomer. The platelet retention test gave better results than those achieved with the elastomer. The haemolysis percentage of the alloy was almost zero. These results indicate that the Ti6A14V alloy is well tolerated by blood.

Experimental evaluation of a gelatin-coated polyester graft used as an arterial sstitute

Protein coating and endothelial cell preseeding have been proposed and studied as improvements to arterial prostheses. In this paper, an impervious polyester vascular graft which had been coated with cross-linked gelatin was compared to a porous one over a period of up to 8 months in dogs. This evaluation involved in vivo methods using radio tracers to study patency and thrombogenicity and in vitro controls of the healing processes. The main advantages offered by coated grafts over uncoated include the absence of preclotting and better biointegration.

Biocompatibility of carbon-carbon materials: Blood tolerability

Carbon-carbon composites are well known in the field of aerospace technology. Such composites have been proposed to be used as biomaterials, particularly in contact with blood. To evaluate their haemocompatibility, samples were tested in vivo and in vitro, using radiotracers. In vivo study showed the accumulation of platelets on the exposed surface material with any surface morphology, whereas platelet concentration in blood remained constant. In vitro study allowed us to distinguish, among entrapped platelets, active adhering platelets from those mechanically retained and it appeared that the bulk structure of materials influenced the adhesion mechanism of platelets.