The paradigm shift brought about by the expansion of tissue engineering and regenerative medicine away from the use of biomaterials, currently questions the value of histopathologic methods in the evaluation of biological changes. To date, the available tools of evaluation are not fully consistent and satisfactory for these advanced therapies. We have developed a new, simple and inexpensive quantitative digital approach that provides key metrics for structural and compositional characterization of the regenerated tissues. For example, metrics provide the tissue ingrowth rate (TIR) which integrates two separate indicators; the cell ingrowth rate (CIR) and the total collagen content (TCC) as featured in the equation, TIR% = CIR% + TCC%. Moreover a subset of quantitative indicators describing the directional organization of the collagen (relating structure and mechanical function of tissues), the ratio of collagen I to collagen III (remodeling quality) and the optical anisotropy property of the collagen (maturity indicator) was automatically assessed as well. Using an image analyzer, all metrics were extracted from only two serial sections stained with either Feulgen&Rossenbeck (cell specific) or Picrosirius Red F3BA (collagen specific). To validate this new procedure, three-dimensional (3D) scaffolds were intraperitoneally implanted in healthy and in diabetic rats. It was hypothesized that quantitatively, the healing tissue would be significantly delayed and of poor quality in diabetic rats in comparison to healthy rats. In addition, a chemically modified 3D scaffold was similarly implanted in a third group of healthy rats with the assumption that modulation of the ingrown tissue would be quantitatively present in comparison to the 3D scaffold-healthy group. After 21 days of implantation, both hypotheses were verified by use of this novel computerized approach. When the two methods were run in parallel, the quantitative results revealed fine details and differences not detected by the semi-quantitative assessment, demonstrating the importance of quantitative analysis in the performance evaluation of soft tissue healing. This automated and supervised method reduced operator dependency and proved to be simple, sensitive, cost-effective and time-effective. It supports objective therapeutic comparisons and helps to elucidate regeneration and the dynamics of a functional tissue.

Purpose Tacks and sutures ensure a strong fixation of meshes, but they can be associated with pain and discomfort. Less invasive methods are now available. Three fixation modalities were compared: the ProGrip™ laparoscopic self-fixating mesh; the fibrin glue Tisseel™ with Bard™ Soft Mesh; and the SorbaFix™ absorbable fixation system with Bard™ Soft Mesh. Materials and methods Meshes (6 cm ×6 cm) were implanted in the preperitoneal space of swine. Samples were explanted 24 hours after surgery. Centered defects were created, and samples (either ten or eleven per fixation type) were loaded in a pressure chamber. For each sample, the pressure, the mesh displacement through the defect, and the measurements of the contact area were recorded. Results At all pressures tested, the ProGrip™ laparoscopic self-fixating mesh both exhibited a significantly lower displacement through the defect and retained a significantly higher percentage of its initial contact area than either the Bard™ Soft Mesh with Tisseel™ system or the Bard™ Soft Mesh with SorbaFix™ absorbable fixation system. Dislocations occurred with the Bard™ Soft Mesh with Tisseel™ system and with the Bard™ Soft Mesh with SorbaFix™ absorbable fixation system at physiological pressure (,225 mmHg). No dislocation was recorded for the ProGrip™ laparoscopic self-fixating mesh. Conclusion At 24 hours after implantation, the mechanical fixation of the ProGrip™ laparoscopic self-fixating mesh was found to be significantly better than the fixation of the Tisseel™ system or the SorbaFix™ absorbable fixation system.

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.

A new biphasic calcium phosphate ceramic material has been developed in our laboratory. It is composed of 60% of hydroxyapatite and 40% of beta-tricalcium phosphate, based on three granulometries (submicron, round microporous 80-200 mu m and macro microporous 0.5-1 mm particles) and hydrated with water leading the formation of a putty filler for bone repair. Biocompatibility and osteogenicity were tested by filling femoral epiphyses critical size bone defect and lumbar muscles in rabbit. After 3, 6 and 12 weeks of implantation, explants were treated for histology. Results revealed the biocompatibility of the material and intensive resorption of the submicron particle fraction followed by important bone ingrowth whereas osteoconduction was provided by the larger particles.

Resorbable osteosynthesis based on PLLA and derivatives will be associated to bone substitute for bone reconstruction. We have performed rand evaluated a composite combining PL DLLA and Biphasic calcium phosphate able to have a), a better controlled hydrolysis in the purpose to preserve on time the mechanical property, and b), for long term efficiency, bone ingrowth at the expense of the osteosynthesis and the associated bone substitute. A new calcium phosphate cement MCPC® was tested with such composite. The novel macroporous calcium phosphate cement MCPC sets to poorly crystalline apatite after mixing the powder component and an aqueous solution. Interconnective macroporosity was induced on time by resorption of one part of the MCPC®. The multiphasic calcium phosphate components in the cement, are resorbed at different rates allowing the replacement by newly formed bone. This study reports the biocompatibility and the interactions of a composite using PL DLLA (Poly [L-Lactide-co-D,L-Lactide] acid) charged with biphasic calcium phosphate granules and a self setting calcium phosphate cement of new generation.

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.

Surface roughness modulates the osseointegration of orthopaedic and dental titanium implants. High surface roughness is currently obtained by blasting of titanium implants with silica or aluminium abrasive particles. This process includes into the surface abrasive particles and may cause the release of cytotoxic silica or aluminium ions in the peri implant tissue. To overcome this drawback, we currently develop an innovative gridblasting process using Biphasic Calcium Phosphate (BCP) particles (RBBM Resorbable and Biocompatible Blast Media) to generate biocompatible roughened titanium surface.This work present the technique of blasting using RBBM particles to provide a roughened surface which does not release cytotoxic elements and (ii) to assess the effects of such a roughened surface for bone osteo integration in critical size rabbit defect. Our results demonstrate that resorbable biphasic calcium phosphate abrasive particles can be used to create titanium surface roughness. This grid blasting process increases surface roughness of titanium implants and offers a non cytotoxic surface for rapid and efficient osteointegration.

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.

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.

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.