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Although autografts are considered to be the gold standard treatment for reconstruction of large bone defects resulting from trauma or diseases, donor site morbidity and limited availability restrict their use. Successful bone repair also depends on sufficient vascularization and to address this challenge, novel strategies focus on the development of vascularized biomaterial scaffolds. This pilot study aimed to investigate the feasibility of regenerating large bone defects in sheep using 3D-printed customized calcium phosphate scaffolds with or without surgical vascularization. Pre-operative computed tomography scans were performed to visualize the metatarsus and vasculature and to fabricate customized scaffolds and surgical guides by 3D printing. Critical-sized segmental defects created in the mid-diaphyseal region of the metatarsus were either left empty or treated with the 3D scaffold alone or in combination with an axial vascular pedicle. Bone regeneration was evaluated 1, 2 and 3 months post-implantation. After 3 months, the untreated defect remained non-bridged while the 3D scaffold guided bone regeneration. The presence of the vascular pedicle further enhanced bone formation. Histology confirmed bone growth inside the porous 3D scaffolds with or without vascular pedicle inclusion. Taken together, this pilot study demonstrated the feasibility of precised pre-surgical planning and reconstruction of large bone defects with 3D-printed personalized scaffolds., Peer Reviewed, Postprint (published version)

Bone regeneration is often required to provide adequate oral rehabilitation before dental implants. Vertical ridge augmentation is the most challenging of all situations, and often requires the use of autologous bone grafting. However, autologous bone grafting induces morbidity, and the harvestable bone is limited in quantity. Alternatives to autologous bone grafting include bovine-bone-derived biomaterials, which provide good clinical results and synthetic bone substitutes that still fail to provide a reliable clinical outcome. Synthetic biomimetic calcium phosphate (SBCP) biomaterials, consisting of precipitated apatite crystals that resemble in composition and crystallinity to the mineral phase of bone, arise as alternatives to both bovine bone and the current sintered bone substitutes. This study aims to compare the vertical bone regeneration capacity of the SBCP (MimetikOss, Mimetis Biomaterials) with that of a deproteinized bovine bone matrix (DBBM, Bio-Oss®; Geistlich Biomaterials) on the calvaria of rats. To model vertical bone augmentation, hemispherical cups were filled with the two types of biomaterial granules and implanted onto the skull of rats, while empty cups were used as controls. After 4 and 8 weeks of healing, bone growth was determined by microcomputed tomography and histomorphometry. After 4 weeks of implantation, a significantly higher bone growth was found in the case of SBCP compared with DBBM and left empty controls. At 8 weeks, no statistically significant differences were found between the two bone substitutes. These results are promising since vertical bone regeneration was faster in the case of SBCP than for DBBM., Peer Reviewed, Postprint (author's final draft)

Successful preliminary studies have encouraged a more translational phase for stem cell research. Nevertheless, advances in the culture of human bone marrow-derived mesenchymal stromal/stem cells (hBM-MSC) and osteoconductive qualities of combined biomaterials can be undermined if necessary cell transportation procedures prove unviable. We aimed at evaluating the effect of transportation conditions on cell function, including the ability to form bone in vivo, using procedures suited to clinical application. hBM-MSC expanded in current Good Manufacturing Practice (cGMP) facilities (cGMP-hBM-MSC) to numbers suitable for therapy were transported overnight within syringes and subsequently tested for viability. Scaled-down experiments mimicking shipment for 18 h at 4 C tested the influence of three different clinical-grade transportation buffers (0.9% saline alone or with 4% human serum albumin [HSA] from two independent sources) compared with cell maintenance medium. Cell viability after shipment was >80% in all cases, enabling evaluation of (1) adhesion to plastic flasks and hydroxyapatite tricalcium phosphate osteoconductive biomaterial (HA/ß-TCP 3D scaffold); (2) proliferation rate; (3) ex vivo osteogenic differentiation in contexts of 2D monolayers on plastic and 3D HA/ß-TCP scaffolds; and (4) in vivo ectopic bone formation after subcutaneous implantation of cells with HA/ß-TCP scaffold into NOD/SCID mice. Von Kossa staining was used to assess ex vivo osteogenic differentiation in 3D cultures, providing a quantifiable test of 3D biomineralization ex vivo as a rapid, cost-effective potency assay. Near-equivalent capacities for cell survival, proliferation, and osteogenic differentiation were found for all transportation buffers. Moreover, cGMP-hBM-MSC transported from a production facility under clinical-grade conditions of 4% HSA in 0.9% saline to a destination 18 h away showed prompt adhesion to HA/ß-TCP 3D scaffold and subsequent in vivo bone formation. A successf, Peer Reviewed, Postprint (published version)

Item does not contain fulltext, Titanium and its alloys, when treated in alkali solutions, are able to form calcium phosphate coatings on their surface after immersion in supersaturated solutions. In this study, the surfaces of titanium alloy discs were modified by an alkali treatment and a radio frequency (RF) plasma procedure (150 W and 13.56 MHz) in N(2), CO(2) or N(2)/O(2) (80/20%) atmospheres. After the alkali treatment, atomic force microscopy showed differences in the surface roughness of the samples. X-ray photoelectron microscopy indicated that the chemical composition of the surfaces changed after the different alkali and RF plasma treatments. The contact angles were also modified by approximately 5 degrees , making the original titanium surface more hydrophilic. Immersion in a supersaturated calcium phosphate solution was used to evaluate the bioactivity of the RF plasma-treated samples in vitro. Alkali-treated samples gave more homogeneous and thick coatings that those without alkali treatment. The use of RF plasma treatments enhanced the bioactivity of the samples, in particular for treatments performed in N(2) or N(2)/O(2) atmospheres. Energy-dispersive X-ray analysis indicated that coatings had Ca/P ratios between the values of octacalcium phosphate and hydroxyapatite. X-ray diffraction confirmed the presence of these two phases in most of the coatings. This study shows that an RF plasma treatment enhanced the bioactivity of titanium surfaces.

Item does not contain fulltext, OBJECTIVES: The surface properties of titanium dental implants are key parameters for rapid and intimate bone-implant contact. The osseointegration of four implant surfaces was studied in the femoral epiphyses of rabbits. MATERIAL AND METHODS: Titanium implants were either grit-blasted with alumina or biphasic calcium phosphate (BCP) ceramic particles, coated with a thin octacalcium phosphate (OCP) layer, or prepared by large-grit sand blasting and acid-etched (SLA). After 2 and 8 weeks of implantation, the bone-implant contact and bone growth inside the chambers were compared. Scanning electron microscopy (SEM) and profilometry showed distinct microtopographies. RESULTS: The alumina-Ti, BCP-Ti and OCP-Ti groups had similar average surface roughness in the 1-2 mum range whereas the SLA surface was significantly higher with a roughness averaging 4.5 microm. Concerning the osseointegration, the study demonstrated a significantly greater bone-to-implant contact for both the SLA and OCP-Ti surfaces as compared with the grit-blasted surfaces, alumina- and BCP-Ti at both 2 and 8 weeks of healing. CONCLUSION: In this animal model, a biomimetic calcium phosphate coating gave similar osseointegration to the SLA surface. This biomimetic coating method may enhance the apposition of bone onto titanium dental implants.

Item does not contain fulltext, AIMS: Surface modifications at the nanometric scale may promote protein adsorption, cell adhesion and thus favor the osseointegration of metal implants. The behavior of osteoblastic cells was studied on mirror-polished (Smooth-SS) and nanostructured (Nano-SS) stainless steel surfaces. MATERIALS & METHODS: The nanostructuration was obtained by anodization. The surfaces were characterized by scanning electron, atomic force microscopy (AFM) and X-ray photoelectron specytoscopy. Osteoblastic cells were cultured on these surfaces. RESULTS & DISCUSSION: AFM showed a regular array of pores on the Nano-SS. Osteoblastic cells spread more rapidly on Nano-SS surfaces than on Smooth-SS surfaces. Cell viability was similar on Smooth-SS and Nano-SS. Alkaline phosphatase activity increased with culture time whatever the substrate but was better enhanced at 21 days on the Nano-SS than on the Smooth-SS. CONCLUSION: This study shows that the nanostructuration of metal implants may improve the adhesion and differentiation of osteoblastic cells.

Item does not contain fulltext, Two porous titanium implants with a pore size diameter of 800 and 1200 microm (Ti800 and Ti1200) and an interconnected network were manufactured using rapid prototyping. Their dimensions and structure matched those of the computer assisted design. The porosity of the implants was around 60%. Their compressive strength and Young's modulus were around 80 MPa and 2.7 GPa, respectively. These values are comparable to those of cortical bone. The implants were implanted bilaterally in the femoral epiphysis of 15 New Zealand White rabbits. After 3 and 8 weeks, abundant bone formation was found inside the rapid prototyped porous titanium implants. For the Ti1200 implants, bone ingrowth was (23.9 +/- 3.5)% and (10.3 +/- 2.8)%, respectively. A significant statistical difference (p < 0.05) was found for bone ingrowth in the Ti1200 between the two delays. The percentage of bone directly apposited on titanium was (35.8 +/- 5.4)% and (30.5 +/- 5.0)%. No significant difference was found for bone-implant contact between the different time periods and pore sizes. This work demonstrates that manufacturing macroporous titanium implants with controlled shape and porosity using a rapid prototyping method is possible and that this technique is a good candidate for orthopedic and maxillofacial applications.