Papers by Author: Serge Baroth

Abstract: Physico-chemical characteristics impact directly or indirectly the bioactive properties of biomaterials, it is then essential to correlate it with their effect in vivo. A panel of biomaterials available on the market, based on Hydroxyapatite (HA) and Tricalcium phosphate (β-TCP) is studied in terms of surface area, hydrophilicity, porosity, zeta potential, crystalline phases and density. This study highlights the dispersity of commercial calcium phosphates (CaP) properties, and demonstrates how the quality criteria required for such bone substitute based on biomimicry concept, whose pores distribution is certainly the more relevant, are often incompletely or not respected according to literature.

Abstract: The main goal of this study was to succeed in the relevant association of well-known osteoconductive biphasic calcium phosphate (BCP) made of Hydroxyapatite (20% HA) and β-Tricalcium Phosphate (80% β-TCP) crystallographic phases and resorbable poly (L-lactide-co-D,L-lactide)(PLDLLA) 3D matrices synthesized by electrospinning. Two types of mineral particles were obtained, BCP new hollow granules, and classical BCP particles. It appeared that hollow shells/PLDLLA composite 3D matrices allowed higher cell adhesion in vitro, thanks to internal concavities and are promising scaffolds in terms of cell carrying.

Abstract: Calcium phosphate bioceramic granules associated with hydrosoluble polymers formed putties currently more used in clinical applications as they are easy to handle (injectability, moldability). In this study, 2 kinds of materials were tested in rabbit bone defects. The first one is InOss (Biomatlante), a microporous biphasic CaP granules (BCP, HA/TCP mixture) with polysaccharidic hydrogel; and the second one is Actifuse ABX (Baxter/Apatech), pure hydroxyapatite granules containing silicate (HA-Si) with blocks copolymer hydrogel (poloxamer), . The aim of this study was to compare osteogenic properties of two kinds of CaP putties containing HA-Si versus BCP and the kinetic of resorption of their hydrogel. Data have demonstrated that both hydrogels increase the handling properties. Bone regeneration was observed in the two types of sample, however at 3 weeks, Actifuse ABX hydrogel was not totally absorbed, while InOss hydrogel was no longer observed. The second difference observed was osteoconduction. Newly formed bone over the time period studied was moreover in close contact with BCP granules than with HA-Si granules. Larger granules resorption on time was observed for BCP compared to HA-Si. Resorption of Actifuse ABX remains limited and explains the faster kinetic of absorption for InOss. This study demonstrates biocompatibility, absorbability and bone ingrowth at the expense of the two types of putty injectable/moldable bioceramic used for bone regeneration.

Abstract: The development of CaP ceramics involved a better control of the process of resorption and bone substitution. Micro Macroporous Biphasic CaP, (MBCP+) is a concept based on an optimum balance of the more stable phase of HA and more soluble TCP. The material is soluble and gradually dissolves in the body, seeding new bone formation as it releases Ca and P ions into the biological medium. The MBCP+ is selected for tissue engineering in a large European research program on osteoinduction and mesenchymal stem cell technology (REBORNE 7^th EU frame work program, Regenerative Bone defects using New biomedical Engineering approaches, www.reborne.org). We have optimized the matrices in terms of their physical, chemical, and crystal properties, to improve cell colonization and to increase kinetic bone ingrowth. The fast cell colonization and resorption of the material are associated to the interconnected macropores structure which enhances the resorption bone substitution process. The micropore content involves biological fluid diffusion and suitable adsorption surfaces for circulating growth factors. The bioceramics developed for this project was fully characterized using X-Ray diffraction, FTIR, X-rays micro tomography, Hg porosimetry, BET specific surface area, compressive mechanical test, and SEM. Preclinical tests on the optimized scaffold were realized in critical size defects in several sites of implantation and animals (rats, rabbits, goats, dogs).The smart scaffold has a total porosity of 73%, constituted of macropores (>100µm), mesopores of 10 to 100µm and high micropores (<10µm) content of more or less 40%. The crystal size is <0.5 to 1 µm and the specific surface area was around 6m²/g. The in vivo experiment indicated higher colonization by osteogenic cells demonstrating suitable matrices for tissue engineering. The HA/TCP ratio of 20/80 was also more efficient for combination with total bone marrow or stem cell cultivation and expansion before to be implanted.

Abstract: An hydrated putty was prepared by mixing submicron particles, rounded particles and granules of Biphasic Calcium Phosphate (BCP) ceramics composed of HA and β-TCP phases. The material filled entirely critical sized defects in the femoral epiphysis of NZW rabbits. After 3, 6 and 12 weeks, histology revealed that submicron particles were rapidly degraded by multinucleated TRAP-positive cells. This osteoclastic resorption stimulated bone ingrowth while the large BCP particles served as scaffold supporting bone healing by osteoconduction.

Abstract: We have developed a new injectable bone substitute combining specific granules of BCP with or without radiopaque elements with a reversible thermo sensitive resorbable carrier such as Pluronic F-127. The composite is liquid at ambient temperature and set as hydrogel at 37°C. Rabbit experiment demonstrates high biocompatibility and bone ingrowth at the expense of the injectable bioceramic composite.

Abstract: We have developed a novel macroporous calcium phosphate cement MCPC® that sets to poorly crystalline apatite after mixing the powder component with an aqueous solution and has interconnective macroporosity We performed cranioplasty on rat model by injecting the new macroporous calcium phosphate cement MCPC®. The mechanical property of the cement is about 12MPa after 24 hours (compression test). The cement matrix is totally transformed into poorly crystalline apatite in 48 hours. This study demonstrates that MCPC® cement was suitable and efficient for parietal bone reconstruction. Its injectability and moldability allows to be used in bone reconstruction surgery and its mechanical properties are compatible to support calvarial reconstruction. In addition, a bone ingrowth onto the BCP granules occurred on time.

Abstract: Dedicated to Minimal Invasive Surgery MIS particularly in spine for vertebroplasty, the surgeons and radiologists ask for improvement of radio opacity, to be sure of the injection site, and to prevent injection in blood vessels. MBCP Gel® is an Injectible biomaterial non self hardening, the biomaterials consists of BCP granules associated with a hydrosoluble polymer. These materials have been shown to be perfectly biocompatible and potentially resorbable and, thanks to their initial plasticity, they assume the shape of the bone defects very easily, eliminating the need to shape the material to adjust to the implantation site. MBCP gels do not have mechanical properties like the hydraulic bone cements. However bone cells are able to invade the spaces created by the disappearance of the polymer carrier. Bone ingrowth takes place all around the granules at the expense of the resorption of the BCP granules. In time, the mechanical property is increased due to the presence of the newly formed bone. This study demonstrates an improvement of MBCP gel by freeze drying and reconstitution using iodine solution or sterile water in a classical model of rabbit bone defects.

Abstract: We performed vertebroplasty on goat model by injecting a new macroporous calcium phosphate cement MCPC®. The mechanical property of the cement is about 12MPa after 24 hours (compression test). The cement matrix is totally transformed into poorly crystallized apatite in 48 hours. This study demonstrates that MCPC cement was suitable and efficient for a spine application. Its injectability allows to be used in mini invasive surgery and its mechanical properties are compatible to support spine strength. In addition, a bone ingrowth onto the BCP granules occurred with time.

Abstract: The purpose of this study ass to investigate the addition of round 80-200m granules shape radiopaque agents (RA) to synthetic Injectable Bone Substitute to improve contrast performance for minimal invasive surgery MIS. Composites were obtained by mixing BaSO4, Bi2O3, Lu2O3 or GdPO4 with calcium deficient apatite CDA which decompose during sintering process in BCP (60% HA, 40% β-TCP). Each composite was characterized: by XRD, FTIR. Biocompatibility was tested in vitro and in vivo in bony site (3 weeks implantation in rats). Primary results show that the suitable radiopaque BCP/RA composite (radiopacity intensity, biological responses) appeared to be BCP/Ba. Next works will complete the current studies on biological performance in association with different kind of resorbable injectable bone substitute as suspension, gel or calcium phosphate cements.