Bone healing dynamics associated with 3 implants with different surfaces: histologic and histomorphometric analyses in dogs.

PURPOSE: This study evaluated differences in bone healing and remodeling among 3 implants with different surfaces: sandblasting and large-grit acid etching (SLA; IS-III Active®), SLA with hydroxyapatite nanocoating (IS-III Bioactive®), and SLA stored in sodium chloride solution (SLActive®). METHODS: The mandibular second, third, and fourth premolars of 9 dogs were extracted. After 4 weeks, 9 dogs with edentulous alveolar ridges underwent surgical placement of 3 implants bilaterally and were allowed to heal for 2, 4, or 12 weeks. Histologic and histomorphometric analyses were performed on 54 stained slides based on the following parameters: vertical marginal bone loss at the buccal and lingual aspects of the implant (b-MBL and l-MBL, respectively), mineralized bone-to-implant contact (mBIC), osteoid-to-implant contact (OIC), total bone-to-implant contact (tBIC), mineralized bone area fraction occupied (mBAFO), osteoid area fraction occupied (OAFO), and total bone area fraction occupied (tBAFO) in the threads of the region of interest. Two-way analysis of variance (3 types of implant surface×3 healing time periods) and additional analyses for simple effects were performed. RESULTS: Statistically significant differences were observed across the implant surfaces for OIC, mBIC, tBIC, OAFO, and tBAFO. Statistically significant differences were observed over time for l-MBL, mBIC, tBIC, mBAFO, and tBAFO. In addition, an interaction effect between the implant surface and the healing time period was observed for mBIC, tBIC, and mBAFO. CONCLUSIONS: Our results suggest that implant surface wettability facilitates bone healing dynamics, which could be attributed to the improvement of early osseointegration. In addition, osteoblasts might become more activated with the use of HA-coated surface implants than with hydrophobic surface implants in the remodeling phase.

Oral tissue response to soft tissue expanders prior to bone augmentation: in vitro analysis and histological study in dogs.

PURPOSE: To determine whether the swelling and mechanical properties of osmotic self-inflating expanders allow or not the induction of intraoral soft tissue expansion in dogs. METHODS: Three different volumes (0.15, 0.25, and 0.42 mL; referred to respectively as the S , M , and L groups) of soft tissue expanders (STEs) consisting of a hydrogel core coated with a silicone-perforated membrane were investigated in vitro to assess their swelling behavior (volume swelling ratio) and mechanical properties (tensile strength, tensile strain). For in vivo investigations, the STEs were subperiosteally inserted for 4 weeks in dogs (n=5). Soft tissue expansion was clinically monitored. Histological analyses included the examination of alveolar bone underneath the expanders and thickness measurements of the surrounding fibrous capsule. RESULTS: The volume swelling ratio of all STEs did not exceed 5.2. In tensile mode, the highest mean strain was registered for the L group (98.03±0.3 g/cm), whereas the lowest mean value was obtained in the S group (81.3±0.1 g/cm), which was a statistically significant difference (P<0.05). In addition, the S and L groups were significantly different in terms of tensile strength (1.5±0.1 g/cm for the S group and 2.2±0.1 g/cm for the L group, P<0.05). Clinical monitoring showed successful dilatation of the soft tissues without signs of inflammation up to 28 days. The STEs remained volumetrically stable, with a mean diameter in vivo of 6.98 mm, close to the in vitro post-expansion findings (6.69 mm). Significant histological effects included highly vascularized collagen-rich fibrous encapsulation of the STEs, with a mean thickness of 0.67±0.12 mm. The bone reaction consisted of resorption underneath the STEs, while apposition was observed at their edges. CONCLUSIONS: The swelling and mechanical properties of the STEs enabled clinically successful soft tissue expansion. A tissue reaction consisting of fibrous capsule formation and bone loss were the main histological events.

Purification of antibody fragments for the reduction of charge variants using cation exchange chromatography.

Recently, antibody fragments have been studied as therapeutic agents because they lack Fc effector function while having affinity similar to their original monoclonal antibody and can be produced using E. coli. Antibody fragments can be purified using affinity chromatography in the capture step, although they need a polishing step because of product-related impurities, mainly charge variants. Unlike monoclonal antibodies, few studies exist regarding the separation of charge variants in antibody variants. In this study, an efficient separation of charge variant method was assessed using a cation exchange chromatography resin with salt and a pH gradient. The SP ImpRes resin and pH gradient exhibited the most effective separation potency using combinations of resin and the separation method. The antibody fragment that did not undergo the charge variant separation process exhibited a difference in the tertiary structure of the protein and in vivo pharmacokinetics. However, the antibody fragment was similar to the reference protein when the charge variant separation process was performed. These results are expected to support efficient charge variant separation of antibody fragments and to be applied to the industrial production of therapeutic antibody fragments.

Periodontal and endodontic pathology delays extraction socket healing in a canine model.

PURPOSE: The aim of the present exploratory study was to evaluate extraction socket healing at sites with a history of periodontal and endodontic pathology. METHODS: The mandibular 4th premolar teeth in 5 adult beagle dogs served as experimental units. Periodontal and endodontic lesions were induced in 1 premolar site in each animal using wire ligatures and pulpal exposure over 3 months (diseased sites). The contralateral premolar sites served as healthy controls. The mandibular 4th premolar teeth were then extracted with minimal trauma, followed by careful wound debridement. The animals were sacrificed at days 1, 7, 30, 60, and 90 post-extraction for analysis, and the healing patterns at the healthy and diseased extraction sites were compared using radiography, scanning electron microscopy, histology, and histometry. RESULTS: During the first 7 days of healing, a significant presence of inflammatory granulation tissue was noted at the diseased sites (day 1), along with a slightly accelerated rate of fibrin clot resolution on day 7. On day 30, the diseased extraction sites showed a greater percentage of persistent fibrous connective tissue, and an absence of bone marrow formation. In contrast, healthy sites showed initial signs of bone marrow formation on day 30, and subsequently a significantly greater proportion of mature bone marrow formation on both days 60 and 90. Radiographs exhibited sclerotic changes adjoining apical endodontic lesions, with scanning electron microscopy showing collapsed Volkmann canals protruding from these regions in the diseased sites. Furthermore, periodontal ligament fibers exhibited a parallel orientation to the alveolar walls of the diseased sites, in contrast to a perpendicular arrangement in the healthy sites. CONCLUSIONS: Within the limitations of this study, it appears that a history of periodontal and endodontic pathology may critically affect bone formation and maturation, leading to delayed and compromised extraction socket healing.

Inhibitory effect of eriodictyol on IgE/Ag-induced type I hypersensitivity.

Mast cells are the principal effector cells involved in the allergic response, through the release of histamine. We investigated the effect of eriodictyol, derived from the painted maple and yerba santa, on mast cell degranulation and on an allergic response in an animal model. We also investigated its effect on the expression of the ceramide kinase (CERK) involved in calcium-dependent degranulation, and on ceramide activation by multiple cytokines. Eriodictyol suppressed the release of beta-hexosaminidase, a marker of degranulation, and the expression of interleukin (IL)-4 mRNA. It inhibited the expression of CERK mRNA, reduced the ceramide concentration in antigen-stimulated mast cells, and suppressed the passive cutaneous anaphylaxis (PCA) reaction in mice in a dose-dependent manner. These results suggest that eriodictyol can inhibit mast cell degranulation through inhibition of ceramide kinase, and that it might potentially serve as an anti-allergic agent.

Idesolide, an isolate of Idesia polycarpa, inhibits apoptosis through induction of intracellular heat shock protein 70 in C2C12 muscle cells.

Muscle disorders, such as muscular dystrophy, are associated with an increase in oxidative stress. Proposed treatments for muscular dystrophy, some in clinical trials, include gene therapy and muscle cell transplantation. In this study, we investigated the effects of idesolide, isolated from the fruits of Idesia polycarpa, on changes that occur in muscle disuse atrophy. We noted protective effects on oxidative stress response and HSP70 regulation. Pre-treatment with idesolide for 24 h maintained cell viability and decreased apoptosis in H(2)O(2)-treated C(2)C(12) muscle cells. The idesolide pretreatment also increased intracellular HSP70 protein. Our results suggest that idesolide inhibits cell death through induction of HSP70 in C(2)C(12) muscle cells. This work is the first to report that idesolide can regulate the decrease in HSP70 that occurs during skeletal muscle atrophy.