Ugi multicomponent reaction to prepare peptide–peptoid hybrid structures with diverse chemical functionalities

Monodisperse sequenced peptides and peptoids present unique nano-structures based on their self-assembled secondary and tertiary structures. However, the generation of peptide and peptoid hybrid oligomers in a sequence-defined manner via Ugi multicomponent reaction has not yet been studied. Herein, we report a synthetic strategy that enables both the modification of peptides as well as the generation of sequence-defined peptide–peptoid hybrid structures. Our synthetic methodology rests on the fusion of solid phase peptide synthesis with Ugi multicomponent reactions. We evidence that a diversity of chemical functionalities can be inserted into peptides or used in the design of peptide–peptoid hybrids exploiting a wide functional array including amines, carboxylic acids, hydrocarbons, carbohydrates as well as polymers, introducing a sequence-defined synthetic platform technology for precision peptoid hybrids

Supramolecular Nanofibrous Peptide/Polymer Hydrogels for the Multiplexing of Bioactive Signals

The ability to provide multiple functions within a single scaffold biomaterial is a major goal in tissue engineering. Self-assembling peptide-based hydrogels are gaining significant attention as three-dimensional biomaterials because they provide a network of nanofibers similar to the native extracellular matrix while allowing the presentation of multiple biochemical cues for cell signaling. Herein, we combine a positively charged peptide amphiphile (PA) and the negatively charged synthetic polymer poly­(sodium 4-styrenesulfonate) (PSS) to fabricate hybrid hydrogels through supramolecular self-assembly. PSS/PA hydrogels show rather high mechanical stiffness while being stable in buffered environment. The sulfonate functionality in PSS promotes hydrogel mineralization which can be controlled if undertaken in standard osteogenic medium. Loading proteins with different charges in the hydrogels reveals their ability to retain and sustain their release and indicates their potential for the controlled delivery of growth factors. Human mesenchymal stem cells encapsulated in PSS/PA hydrogels remain viable. The biomimetic nanofibrous structure of the hydrogels, together with multiplexing of bioactive signals, can provide a suitable environment for stem cell differentiation

Evaluation of Adjunctive and Alternative Techniques in Periodontal Therapy

Mechanical debridement of supragingival but predominantly subgingival bacterial plaque and calculus has been the mainstay of traditional treatment for periodontal disease. Practical difficulties and occasionally lack of response or recurrence of disease in some patients have made investigators search for more effective alternative or adjunctive methods of therapy. In this thesis, two modern approaches, local antimicrobial delivery systems, as adjuncts to scaling and root planing, and the Nd:YAG laser, as an alternative to scaling and root planing, were investigated. The study designed to investigate subgingival antimicrobial systems was of randomised parallel design and sought to evaluate the efficacy of 3 locally delivered antimicrobial systems as adjuncts to scaling and root planing in the treatment of sites with persistent periodontal lesions. Fifty-four patients with 4 pockets > 5 mm and bleeding on probing (BOP) and/or suppuration were randomised in 4 treatment groups including: scaling and root planing either alone (S) or plus application of 25% tetracycline fibre (S&T) or 2% minocycline gel (S&Mi) or 25% metronidazole gel (SScMe) . All treatments resulted in significant improvement in pocket depth (PD), attachment level (AL) , BOP and the Modified Gingival Index (MGI) scores which were maintained until the end of the 6-month follow-up period, although some rebound towards baseline occurred in all groups at the 6-month visit. The improvements in clinical parameters were greater in the S&T group than other groups at any time point. At the 6- week visit, the pocket depth reduction (APD) was significantly greater in the S&T group than in the S group (p=0.002). There was no significant difference between groups in APD at 3 and 6-month visits. The difference between groups in improvement of AL (AAL) or BOP was not significant at any time point. The frequency of sites with suppuration reached zero only in the S&T group at the 6-week and 3-month visits. No serious adverse effects were observed or reported in any of the treatment groups. The S&T was the most time-consuming treatment. While all 3 locally applied antimicrobial systems appear to offer some benefit over scaling and root planing alone, S&T treatment demonstrated the greatest advantage in the treatment of persistent periodontal lesions, particularly at suppurating sites. A further aim of the study was to evaluate the effect of smoking on the outcome of periodontal therapy. Regardless of the type of treatment, APD and AAL were consistently greater in non-smoker subjects than smokers. The General Linear Model analysis was used for APD and AAL to take into account, variations in the treatments, number of smokers per group and baseline pocket depth. There was consistently a significant interaction between the 'smoking' and the 'baseline PD'. Further analysis using linear regression indicated that while there was a significant relationship between the baseline PD and the APD or AAL among the non-smokers, a weak and insignificant relationship existed among the smoker subjects. These results strongly suggest that smoking is a factor to consider in the determination of prognosis of periodontal treatment, particularly in deep pockets. The aim of the first laser study was to evaluate the effects of Nd:YAG laser treatment on sub-gingival calculus, cementum and dentine, in vitro at different power settings and durations. Eight different laser treatment settings were tested on subgingival calculus, cementum and dentine specimens and were assessed using scanning electron microscopy (SEM). Micrographs were taken from each treated site at x100 and x750 magnifications. An arbitrary scale (from 0 to 3) was used to score the degree of damage caused by the laser. Generally, the laser caused greater damage on calculus than either cementum or dentine specimens, although in cases of complete ablation of calculus, the underlying cementum was ablated too. This may limit selective calculus removal without damaging the underlying dental tissues. Three-way analysis of variance showed that for calculus, the power setting, pulse repetition, and the duration of exposure, contributed independently to the mean damage score in an additive way. The results also showed that there was variability in susceptibility of different teeth and different parts of each tooth, which was true for calculus, cementum and dentine. This variability may preclude the safe and predictable removal of calculus by specific laser settings. (Abstract shortened by ProQuest.)

Fixtureless geometric inspection of nonrigid parts using "generalized numerical inspection fixture"

Free-form nonrigid parts form the substance of today’s automotive and aerospace industries. These parts have different shapes in free state due to their dimensional and geometric variations, gravity and residual strains. For the geometric inspection of such compliant parts, special inspection fixtures, in combination with coordinate measuring systems (CMM) and/or optical data acquisition devices (scanners) are used. This inevitably causes additional costs and delays that result in a lack of competitiveness in the industry. The goal of this thesis is to facilitate the dimensional and geometrical inspection of flexible components from a point cloud without using a jig or secondary conformation operation. More specifically, we aim to develop a methodology to localize and quantify the profile defects in the case of thin shells which are typical to the aerospace and automotive industries. The presented methodology is based on the fact that the interpoint geodesic distance between any two points of a shape remains unchangeable during an isometric deformation. This study elaborates on the theory and general methods for the metrology of nonrigid parts. We have developed a Generalized Numerical Inspection Fixture (GNIF), a robust methodology which merges existing technologies in metric and computational geometry, nonlinear dimensionality reduction techniques, and finite element methods to introduce a general approach to the fixtureless geometrical inspection of nonrigid parts

Geometrical inspection of flexible parts using intrinsic geometry

The tolerancing of mechanical parts is one of the major problems in mode mindustry . It's economic consequences are important to the manufacturing sector which sustains major transformations imposed by market globalization and technology evolution (CAD, CMM, 3D Scanners, etc.). Today, we know that product performance optimization requires a consideration of the inherent variations in manufacturing processes, hence quality control throughout the development process and manufacturing. Currently, the geometric inspection oiflexible (or nonrigid) mechanical parts, such as thin-walled skins of airplane or car bodies is still limited to the use of relatively expensive special inspection fixtures, which simulate the use state, applying the same constraints that reflect assembly information. Subsequently, contact measuring or scanning is performed. Simulating this use state means that, deformation effects due to flexibility are eliminated. In this way, defects in the manufacturing process are detectable. The goal of this thesis is to facilitate the dimensional and geometrical inspection of flexible components from a point cloud without using a jig or secondary conformation operation. More specifically, we aim to develop a methodology to localize and quantify the profile defects in the case of thin shells which are typical to the aerospace and automotive industries. To this end, we implemented an idea that we call Numerical Inspection Fixtures. We use geodesic distances to detect the intrinsic similarities between a part in a free state which includes the effects of gravity, intemal constraints and manufacturing defects, and the same part as nominally defined by a CAD model. This thesis develops the theoretical foundation of the proposed methods and related algorithms. We used an approach already used in medical image processing to identify minimum geodesic distance and statistics (Multidimensional Scaling) to analyze the similarities and dissimilarities between two objects, as well as the finite element method to reach a general approach for the inspection of nonrigid parts. Two methods are proposed with numerical validations

Evaluating the Efficacy of a Modified Piezo-Puncture Method on the Rate of Tooth Movement in Orthodontic Patients: A Clinical Study

Objective:Owing to the increasing demand from orthodontic patients for a more rapid treatment, many studies have focused on accelerated tooth movement. Currently, one of the prevalent methods to achieve accelerated tooth movement is piezo-puncture. The aim of the present study was to evaluate the effect of a modified piezo-puncture method on tooth movement rate and type during canine retraction.Methods:A total of 17 patients who required fixed orthodontic treatment with extraction of the maxillary first premolars were included in the study. Following a split-mouth design, upper canines were retracted with Ni–Ti coil spring that applied 150 g of force on each side (piezo-puncture on one side and contralateral side served as the control). Then, the rates of tooth movement, canine angulation and rotation, and anchorage loss were evaluated at T0 (before the intervention), T1 (1 month after the intervention), and T2 (2 months after the intervention). For calculating the canine movement rate, either the distance between the canine and the lateral incisor or the space between the second premolar and the canine was measured. In addition, pain perception was documented by Visual Analog Scale. Data were analyzed using the Kolmogorov–Smirnov normality test, Spearman correlation test, paired sample t-test, and Wilcoxon signed-rank test.Results:No significant acceleration was observed in canine movement, canine tipping, rotation, or anchorage loss of molar in different times.Conclusion:Considering the limitations of the study, the application of piezo-puncture employing the protocol used in the present study failed to accelerate tooth movement and to decrease the unfavorable tipping, rotation, and molar anchorage loss

Piezopuncture-Assisted Canine Distalization in Orthodontic Patients: Two Case Reports

With the increasing number of young adults seeking orthodontic treatment to improve their smile esthetics or oral function, the time spent wearing brackets is one of the biggest challenges for these patients. Various surgical techniques have been developed over the years to accelerate tooth movement and reduce the total treatment time. A newly introduced, minimally invasive procedure namely piezopuncture, which uses a piezosurgical tool to create multiple cortical punctures through the gingiva, is presented in this report of two extraction cases

Nanostructured interfacial self-assembled peptide-polymer membranes for enhanced mineralization and cell adhesion

This work was supported by national funds through the Portuguese Foundation for Science and Technology (FCT) under the scope of the project PTDC/CTM-BIO/0814/2012 and by the European Regional Development Fund (ERDF) through the Operational Competitiveness Programme “COMPETE” (FCOMP-01-0124-FEDER-028491). J. Borges and R. P. Pirraco gratefully acknowledge funding support from FCT for postdoctoral (SFRH/BPD/103604/2014) and investigator (IF/00347/2015) grants, respectively. Y. Shi acknowledges China Scholarship Council for her PhD scholarship (no. 201307060020). H. S. Azevedo also acknowledges financial support from the EU-funded project “SuprHApolymers” (PCIG14-GA-2013-631871) and A. Mata acknowledges the European Research Council Starting Grant “STROFUNSCAFF” and the Marie Curie Career Integration Grant “BIOMORPH”

Clinical and histological evaluation of increase in the residual ridge width using mineralized corticocancellous block allografts: A pilot study

Background. Lateral ridge augmentation is conventionally accomplished by means of autogenous bone grafts. However, due to its complications, the application of autogenous bone graft substitutes, e.g. mineralized corticocancellous allograft, is recommended. Methods. In the present study, twelve patients were included, with insufficient alveolar ridge widths in the designated sites for dental implant placement. During the primary surgery, mineralized corticocancellous block allografts were fixed in deficient sites with titanium screws and resorbable collagen membranes were used to cover the blocks. After a period of six months, a flap was raised and variations in ridge width values was measured. Finally, a micro-biopsy was obtained from the sites for histologic investigation prior to preparing them for subsequent implant placement. Results. All the applied blocks were incorporated into the underlying bone except for one. A statistically significant difference was seen between the average ridge widths before placing the allografts compared with that of implant placement stage (2.62±1.02 mm vs. 7.75±1.63 mm, respectively). Vital bone tissue was detected in all the histological specimens obtained from the interface of blocks and the underlying bone. Conclusion. The results suggest that mineralized corticocancellous block allografts might be used as scaffolds for bone growth and ridge width augmentation

Engineered In vitro Models for Pathological Calcification: Routes Toward Mechanistic Understanding

Physiological calcification plays an essential part in the development of the skeleton and teeth; however, the occurrence of calcification in soft tissues such as the brain, heart, and kidneys associates with health impacts, creating a massive social and economic burden. The current paradigm for pathological calcification focuses on the biological factors responsible for bone-like mineralization, including osteoblast-like cells and proteins inducing nucleation and crystal growth. However, the exact mechanism responsible for calcification remains unknown. Toward this goal, this review dissects the current understanding of structure–function relationships and physico-chemical properties of pathologic calcification from a materials science point of view. We will discuss a range of potential mechanisms of pathological calcification, with the purpose of identifying universal mechanistic pathways that occur across multiple organs/tissues at multiple length scales. The possible effect of extracellular components in signaling and templating mineralization, as well as the role of intrinsically disordered proteins in calcification, is reviewed. The state-of-the-art in vitro models and strategies that can recreate the highly dynamic environment of calcification are identified