Anders Verket

Porous ceramic titanium dioxide scaffolds promote bone formation in rabbit peri-implant cortical defect model.

Titanium oxide (TiO₂) scaffolds have previously been reported to exhibit very low mechanical strength. However, we have been able to produce a scaffold that features a high interconnectivity, a porosity of 91% and a compressive strength above 1.2 MPa. This study analyzed the in vivo performance of the porous TiO₂ scaffolds in a peri-implant cortical defect model in the rabbit. After 8 weeks of healing, morphological microcomputed tomography analyses of the defects treated with the TiO₂ scaffolds had significantly higher bone volume, bone surface and bone surface-to-volume ratio when compared to sham, both in the cortical and bone marrow compartment. No adverse effects, i.e. tissue necrosis or inflammation as measured by lactate dehydrogenase activity and real-time reverse transcription polymerase chain reaction analysis, were observed. Moreover, the scaffold did not hinder bone growth onto the adjacent cortical titanium implant. Histology clearly demonstrated new bone formation in the cortical sections of the defects and the presence of newly formed bone in close proximity to the scaffold surface and the surface of the adjacent Ti implant. Bone-to-material contact between the newly formed bone and the scaffold was observed in the histological sections. Islets of new bone were also present in the marrow compartment albeit in small amounts. In conclusion, the present investigation demonstrates that TiO₂ scaffolds osseointegrate well and are a suitable scaffold for peri-implant bone healing and growth.

Bone formation in TiO2 bone scaffolds in extraction sockets of minipigs

The osteoconductive capacity of TiO(2) scaffolds was investigated by analysing the bone ingrowth into the scaffold structure following their placement into surgically modified extraction sockets in Gottingen minipigs. Non-critical size defects were used in order to ensure sufficient bone regeneration for the evaluation of bone ingrowth to the porous scaffold structure, and sham sites were used as positive control. Microcomputed tomographic analysis revealed 73.6±11.1% of the available scaffold pore space to be occupied by newly formed bone tissue, and the volumetric bone mineral density of the regenerated bone was comparable to that of the native cortical bone. Furthermore, histological evidence of vascularization and the presence of bone lamellae surrounding some of the blood vessels were also observed within the inner regions of the scaffold, indicating that the highly interconnected pore structure of the TiO(2) scaffolds supports unobstructed formation of viable bone tissue within the entire scaffold structure. In addition, bone tissue was found to be in direct contact with 50.0±21.5% of the TiO(2) struts, demonstrating the good biocompatibility and osteoconductivity of the scaffold material.

Enhanced Osteoblast Differentiation on Scaffolds Coated with TiO2 Compared to SiO2 and CaP Coatings

The aim was to compare the protein release from normal human osteoblasts (NHO) cultured on scaffolds with similar morphology but different coatings. Different ceramic coatings; TiO2, SiO2 and calcium phosphate (CaP); Ca9HPO4(PO4)5OH, were applied to porous TiO2 scaffolds prepared by polymer sponge replication. NHO were cultured on scaffolds in triplicates. The concentration of cytokines and Ca2+, and alkaline phosphatase (ALP) activity in the cell media was quantified. The secretion of osteopontin, osteoprotegerin, vascular endothelial growth factor and interleukin-6 was higher from NHO on TiO2 compared to SiO2 and CaP. The secretion from cells on the three scaffolds was, however, either similar or lower than the control cells cultured on plastic. The Ca2+ concentration was higher in cell media on CaP the first week, and no difference in ALP activity was observed. TiO2 coating induced a higher secretion of factors indicating enhanced osteoblast differentiation as compared to CaP and SiO2.

Osseointegration of dental implants in extraction sockets preserved with porous titanium granules – an experimental study

OBJECTIVES This study investigated osseointegration of dental implants inserted in healed extraction sockets preserved with porous titanium granules (PTG). MATERIAL AND METHODS Three adult female minipigs (Gøttingen minipig; Ellegaard A/S, Dalmose, Denmark) had the mandibular teeth P2, P3 and P4 extracted. The extraction sockets were preserved with metallic PTG (Tigran PTG; Tigran Technologies AB, Malmö, Sweden) n = 12, heat oxidized white porous titanium granules (WPTG) (Tigran PTG White) n = 12 or left empty (sham) n = 6. All sites were covered with collagen membranes (Bio-Gide; Geistlich Pharma, Wolhausen, Switzerland) and allowed 11 weeks of healing before implants (Straumann Bone Level; Straumann, Basel, Switzerland) were inserted. The temperature was measured during preparation of the osteotomies. Resonance frequency analysis (RFA, Osstell; Osstell AB, Gothenburg, Sweden) was performed at implant insertion and at termination. After 6 weeks of submerged implant healing, the pigs were euthanized and jaw segments were excised for microCT and histological analyses. RESULTS In the temperature and RFA analyses no significant differences were recorded between the test groups. The microCT analysis demonstrated an average bone volume of 61.7% for the PTG group compared to 50.3% for the WPTG group (P = 0.03) and 57.1% for the sham group. Histomorphometry demonstrated an average bone-to-implant contact of 68.2% for the PTG group compared to 36.6% for the WPTG group and 60.9% for the sham group (n.s). Eight out of ten implants demonstrated apical osseous defects in the WPTG group, but similar defects were observed in all groups. CONCLUSIONS PTG preserved extraction sockets demonstrate a similar outcome as the sham control group for all analyses suggesting that this material potentially can be used for extraction socket preservation prior to implant installment. Apical osseous defects were however observed in all groups including the sham group, and a single cause could not be determined.

Maxillary sinus augmentation with porous titanium granules: a microcomputed tomography and histologic evaluation of human biopsy specimens.

PURPOSE The aim of this study was to assess bone ingrowth into porous titanium granules used for maxillary sinus augmentation. MATERIALS AND METHODS Eighteen biopsy specimens from 17 patients participating in a clinical trial on sinus augmentation using porous titanium granules (PTG) were received in the laboratory. The specimens (trephine cores of 4.5 mm) were obtained 6 months after PTG placement. After being embedded in methacrylate, the samples were scanned in a microcomputed tomography (micro-CT) scanner. Specimens were then cut along the long axis and central slices were ground to 70 μm before staining with hematoxylin and eosin. RESULTS The micro-CT analysis demonstrated an average bone fill of 19% (standard deviation [SD] 5.8%), whereas the graft material occupied 22.7% (SD 4.7%). The volume of newly formed bone decreased with the distance from the residual bone of the sinus floor. Two-dimensional histomorphometric analysis demonstrated a mean area of new bone of 16.1% (SD 9.4%). The PTG alone occupied 25.9% of the total mean area (SD 6.1%). The newly formed bone consisted mainly of woven bone growing in close contact with the granules and bridging the intergranular space. The remaining area was occupied predominantly by nonmineralized connective tissue. There were no signs of inflammation in any of the biopsy specimens. CONCLUSIONS After 6 months, new bone had formed at a similar rate and quality as has been reported for other well-recognized bone graft substitutes. The new bone formed in close contact with the PTG, suggesting that the material is osteoconductive.

Alginate hydrogel enriched with enamel matrix derivative to target osteogenic cell differentiation in TiO2 scaffolds

The purpose of bone tissue engineering is to employ scaffolds, cells, and growth factors to facilitate healing of bone defects. The aim of this study was to assess the viability and osteogenic differentiation of primary human osteoblasts and adipose tissue–derived mesenchymal stem cells from various donors on titanium dioxide (TiO2) scaffolds coated with an alginate hydrogel enriched with enamel matrix derivative. Cells were harvested for quantitative reverse transcription polymerase chain reaction on days 14 and 21, and medium was collected on days 2, 14, and 21 for protein analyses. Neither coating with alginate hydrogel nor alginate hydrogel enriched with enamel matrix derivative induced a cytotoxic response. Enamel matrix derivative–enriched alginate hydrogel significantly increased the expression of osteoblast markers COL1A1, TNFRSF11B, and BGLAP and secretion of osteopontin in human osteoblasts, whereas osteogenic differentiation of human adipose tissue–derived mesenchymal stem cells seemed unaffected by enamel matrix derivative. The alginate hydrogel coating procedure may have potential for local delivery of enamel matrix derivative and other stimulatory factors for use in bone tissue engineering.

Titanium Granules for Augmentation of the Maxillary Sinus – A Multicenter Study

BACKGROUND Biomaterials are commonly used to augment the maxillary sinus floor prior to or in conjunction with dental implant installation. Recently, porous titanium granules (PTGs) have been used in oral implant surgery to stabilize implants and function as an osteoconductive matrix. PURPOSE To evaluate if PTGs can be safely used in a larger population of patients, treated by different surgeons, when sinus floor augmentation was required in conjunction with implant installation. The primary endpoint was 12-month survival rate of the dental implants. Biopsies for histology were taken from the augmented area. MATERIALS AND METHODS At five centers, 40 subjects with uni or bilateral posterior edentulism and atrophy of the posterior maxilla (3-6 mm) were enrolled. In a single-stage procedure, PTG and one to three dental implants were installed in each quadrant. In total, 70 implants were included in the study. RESULTS One immobile implant was removed. The mean marginal bone loss was 0.5 mm and 0.8 mm, on the mesial and distal side, respectively. Histologically, all biopsies demonstrated bone ingrowth. CONCLUSIONS The results suggest that PTG can be safely and effectively used as augmentation material in the sinus floor when used with dental implants in a one-stage procedure.

Dimensional Ridge Preservation with a Novel Highly Porous TiO 2 Scaffold: An Experimental Study in Minipigs

Despite being considered noncritical size defects, extraction sockets often require the use of bone grafts or bone graft substitutes in order to facilitate a stable implant site with an aesthetically pleasing mucosal architecture and prosthetic reconstruction. In the present study, the effect of novel TiO2 scaffolds on dimensional ridge preservation was evaluated following their placement into surgically modified extraction sockets in the premolar region of minipig mandibles. After six weeks of healing, the scaffolds were wellintegrated in the alveolar bone, and the convex shape of the alveolar crest was preserved. The scaffolds were found to partially preserve the dimensions of the native buccal and lingual bone walls adjacent to the defect site. A tendency towards more pronounced vertical ridge resorption, particularly in the buccal bone wall of the nongrafted alveoli, indicates that the TiO2 scaffold may be used for suppressing the loss of bone that normally follows tooth extraction.

Impact of particulate deproteinized bovine bone mineral and porous titanium granules on early stability and osseointegration of dental implants in narrow marginal circumferential bone defects

The use of two particulate bone graft substitute materials in experimental narrow marginal peri-implant bone defects was investigated with respect to early bone healing and implant stability. Porous titanium granules, oxidized white porous titanium granules (WPTG), and demineralized bovine bone mineral (DBBM) were characterized in vitro, after which the two latter materials were tested in experimental peri-implant bone defects in six minipigs, with empty defects as control. After mandibular premolar extraction, the top 5mm of the alveoli were widened to 6mm in diameter, followed by the placement of six implants, three on each side, in each pig. Six weeks of healing was allowed. The WPTG showed better mechanical properties. No significant differences in resonance frequency analysis were found directly after compacting or healing, and similar quantities of defect bone formation were observed on micro-computed tomography for all groups. Histomorphometric analysis demonstrated a more coronal bone-to-implant contact in the DBBM group, which also displayed more defect bone fill as compared to the WPTG group. The better mechanical properties observed for WPTG appear of negligible relevance for the early stability and osseointegration of implants.