Protein Grafting Techniques: From Peptide Epitopes to Lasso-Grafted Neobiologics.

Protein engineering techniques have vastly expanded their domain of impact, notably following the success of antibodies. Likewise, smaller peptide therapeutics have carved an increasingly significant niche for themselves in the pharmaceutical landscape. The concept of grafting such peptides onto larger protein scaffolds, thus harvesting the advantages of both, has given rise to a variety of protein engineering strategies that are reviewed herein. We also describe our own "Lasso-Grafting" approach, which combines traditional grafting concepts with mRNA display to streamline the production of multiple grafted drug candidates for virtually any target.

Trueness of the Combined Intra- and Extraoral Scanning Technique for Transferring Subgingival Contours from Provisional Restorations to Definitive Restorations

PURPOSE: To compare the morphologic trueness of provisional and definitive restorations constructed with conventional custom impression techniques to those constructed with intra- and extraoral scanning (IEOS), which can digitally transfer the subgingival morphology of the provisional restoration to the definitive restoration. MATERIALS AND METHODS: Provisional restorations were fabricated on typodonts in which implants were placed. In the conventional method, a customized impression coping was produced by using polymethyl methacrylate resin to transfer the subgingival contour of the provisional restoration. Impressions were taken with silicone impression material, and definitive restorations were made by CAM. The IEOS technique was performed as previously reported. In brief, three individually scanned stereolithography (STL) files were superimposed in CAD software to transfer the morphology of the provisional restoration to the definitive restoration. Definitive restorations were then made by CAM. The provisional and definitive restorations were both scanned by IOS. Scanned data files were superimposed with morphometry software, and the distortions were measured. Student t test was used for statistical analysis. RESULTS: The subgingival morphologies of definitive restorations prepared by the conventional method showed significant negative distortions compared to definitive restorations prepared by the IEOS technique. CONCLUSION: The IEOS technique can more accurately transfer the subgingival contour of provisional restorations to definitive restorations compared to the conventional customized impression coping technique.

Therapeutic Effect of Benidipine on Medication-Related Osteonecrosis of the Jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is an intractable disease that is typically observed in patients with osteoporosis or tumors that have been treated with either bisphosphonate (BP) or antiangiogenic medicine. The mechanism of MRONJ pathogenesis remains unclear, and no effective definitive treatment modalities have been reported to date. Previous reports have indicated that a single injection of benidipine, an antihypertensive calcium channel blocker, in the vicinity of a tooth extraction socket promotes wound healing in healthy rats. The present study was conducted to elucidate the possibility of using benidipine to promote the healing of MRONJ-like lesions. In this study, benidipine was administered near the site of MRONJ symptom onset in a model rat, which was then sacrificed two weeks after benidipine injection, and analyzed using histological sections and CT images. The analysis showed that in the benidipine groups, necrotic bone was reduced, and soft tissue continuity was recovered. Furthermore, the distance between epithelial edges, length of necrotic bone exposed in the oral cavity, necrotic bone area, and necrotic bone ratio were significantly smaller in the benidipine group. These results suggest that a single injection of benidipine in the vicinity of MRONJ-like lesions can promote osteonecrotic extraction socket healing.

Primary stability of different implant macrodesigns in a sinus floor elevation simulated model: an ex vivo study.

BACKGROUND: A novel type of implant (Straumann® BLX implant) has been developed for certain stability from the mechanical and biological aspects and is expected for the implant placement in atrophic maxilla with sinus floor elevation (SFE). PURPOSE: The aim of this study was to evaluate the primary stability in the implants with different macrodesigns in an SFE simulated model. Primary stabilities defined as maximum insertion torque (MIT) and implant stability quotient (ISQ) were compared between this novel type of implant and other types. MATERIALS AND METHODS: Five types of Straumann® 10 mm length implants (Standard Plus; SP, Tapered Effect; TE, Bone Level; BL, Bone Level Tapered; BLT and BLX) and two types of Straumann® 6 mm length implants (SP short, BLX short) were used in this study. Each implant was inserted through 5 mm-thick porcine iliac crest blocks (an SFE simulated model). Primary stability was evaluated by using MIT and ISQ. RESULTS: The mean value of MIT for BLX group showed significantly higher values than SP, BL (p < 0.01), and TE (p < 0.05) groups. The mean value of ISQ for BLX group was significantly higher than the other groups (p < 0.01). The mean value of MIT and ISQ for BLX and BLX short group were significantly higher than those for SP and SP short group (p < 0.01). CONCLUSIONS: In an SFE simulated ex vivo model, BLX group showed the highest values. These results suggest that implant selection can play a crucial role in the achievement of primary stability during SFE and simultaneous implant placement.

Therapeutic effect of fluvastatin on medication-related osteonecrosis of the jaw.

BACKGROUND: Refractory jaw osteonecrosis that occurs in osteoporotic or cancer patients treated with bisphosphonates is called medication-related osteonecrosis of the jaw but its underlying mechanism is unclear. Statins, therapeutic agents for dyslipidemia, lower blood low-density lipoprotein cholesterol. Fluvastatin promotes the healing of tooth extraction sockets and reduces the risk of developing medication-related osteonecrosis of the jaw-like lesions. We used a rat model to investigate whether injecting fluvastatin at extraction sites promoted the healing of medication-related osteonecrosis of the jaw-like lesions. METHODS: Upper first molars of rats administered zoledronate and dexamethasone for 2 weeks were extracted. Two weeks after tooth extraction, rats with medication-related osteonecrosis of the jaw-like lesions (bone exposure) were included in this study. A single injection of fluvastatin was administered in the vicinity of the medication-related osteonecrosis of the jaw-like onset site in rats. RESULTS: The distance between the edges of the epithelia, the length of the necrotic bone exposed toward the oral cavity, the area of the necrotic bone, and the necrotic bone ratio were significantly smaller in the fluvastatin-administered group compared with the saline group. A single application of fluvastatin near the site of medication-related osteonecrosis of the jaw onset showed a tendency to close the epithelium, reduce necrotic bone, and form new bone, even when symptoms had already developed. CONCLUSION: This study suggests that a single topical administration of fluvastatin may be a novel treatment for medication-related osteonecrosis of the jaw.

The Significance of Posterior Occlusal Support of Teeth and Removable Prostheses in Oral Functions and Standing Motion.

The purpose of this study was to evaluate the effect of posterior occlusal support of natural teeth and artificial teeth on oral functions and standing motion. Patients who had been treated with removable prostheses were enrolled as the subjects. Their systemic conditions (body mass index (BMI) and skeletal muscle mass index (SMI)) were recorded. The subjects were classified into two groups according to a modified Eichner index: B1-3 (with posterior occlusal support) and B4C (without posterior occlusal support). Maximum occlusal force (MOF), masticatory performance (MP), and standing motion (sway and strength) were evaluated for cases with and without removable prostheses. There were no significant differences in BMI and SMI between the B1-3 group and the B4C group. The subjects with removable prostheses demonstrated significantly higher values in MOF, MP, and sway and strength than the subjects without removable prostheses. The comparison of oral functions between the B1-3 group and the B4C group revealed that the positive effect of posterior occlusal support of natural teeth and removable prostheses and the significant positive effects of posterior occlusal support on standing motion were partly observed in these comparisons. Posterior occlusal support of natural teeth and even of removable prostheses may contribute to the enhancement of oral functions and standing motion.

Preventive effect of fluvastatin on the development of medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) occurs in patients undergoing oral surgery while medicated with bisphosphonate, denosumab or anti-angiogenic agents. We employed a MRONJ-like rat model to investigate whether injecting fluvastatin at extraction sites prevents MRONJ-like lesion. A MRONJ-like model was created by treating rats with zoledronate and dexamethasone, extracting teeth, and immediately injecting fluvastatin at the extraction site. The experimental group comprised three subgroups treated with low (0.1 mg/kg; FS-L), medium (1.0 mg/kg; FS-M) and high concentrations (10 mg/kg; FS-H) of fluvastatin. Necrotic bone exposure was significantly lower in the FS-M (p = 0.028) and FS-H (p = 0.041) groups than in the MRONJ group. The distance between the edges of the epithelial surfaces was significantly shorter in the FS-M (p = 0.042) and FS-H (p = 0.041) groups. The area of necrotic bone and the necrotic bone ratio were significantly smaller in the FS-H group (p = 0.041 and p = 0.042 respectively). Bone volume fraction calculated on µ-CT images was significantly larger in the FS-H group than in the MRONJ group (p = 0.021). Our findings suggest that a single local injection of fluvastatin following tooth extraction can potentially reduce the chance of developing MRONJ-like lesion in rats.

Effect of a Single Injection of Benidipine-Impregnated Biodegradable Microcarriers on Bone and Gingival Healing at the Tooth Extraction Socket.

Objective: A dihydropyridine-type calcium channel blocker, benidipine (BD), is extensively used in hypertension therapy. In vitro study reported BD promoting bone metabolism. We evaluated the effect of sustained release of BD-loaded poly(lactic-co-glycolic acid) (PLGA) microcarriers on the promotion of bone and gingival healing at an extraction socket in vivo. In addition, the effect of BD on osteoblasts, osteocytes, fibroblasts, and epithelial cells was evaluated in vitro. Approach: The maxillary first molar of rats was extracted. Next, PLGA microcarriers containing BD were directly injected into the gingivobuccal fold as a single dose. After injection, bone and soft-tissue healing was histologically evaluated. Effect of BD on proliferation, migration, and gene expression of gingival and bone cell was also examined in vitro. Results: After tooth extraction, BD significantly augmented bone volume and density, and also epithelial wound healing. During in vitro studies, BD promoted significant proliferation and migration of fibroblasts and epithelial cells. Real-time RT-PCR revealed that BD upregulated messenger RNA expression of Ahsg (alpha 2-HS glycoprotein) and Csf2 (colony-stimulating factor 2) in osteoblasts. Innovation: The prevention of bone and soft-tissue reduction associated with tooth extraction has been eagerly anticipated in the field of dentistry. This study first reported the effect of BD on extraction socket healing. Conclusion: A single dose of topically administered BD-loaded PLGA microcarriers promoted bone and soft-tissue healing at the extraction site of tooth.