Surface Topography Has Less Influence on Peri-Implantitis than Patient Factors: A Comparative Clinical Study of Two Dental Implant Systems.

OBJECTIVES: This study aims to assess the risk of peri-implantitis (PI) onset among different implant systems and evaluate the severity of the disease from a population of patients treated in a university clinic. Furthermore, this study intends to thoroughly examine the surface properties of the implant systems that have been identified and investigated. MATERIAL AND METHODS: Data from a total of six hundred and 14 patients were extracted from the Institute of Clinical Dentistry, Dental Faculty, University of Oslo. Subject- and implant-based variables were collected, including the type of implant, date of implant installation, medical records, recall appointments up to 2022, periodontal measurements, information on diabetes, smoking status, sex, and age. The outcome of interest was the diagnosis of PI, defined as the occurrence of bleeding on probing (BoP), peri-implant probing depth (PD) ≥ 5 mm, and bone loss (BL). Data were analyzed using multivariate linear and logistic regression. Scanning electron microscopy, light laser profilometer, and X-ray photoelectron spectroscopy were utilized for surface and chemical analyses. RESULTS: Among the patients evaluated, 6.8% were diagnosed with PI. A comparison was made between two different implant systems: Dentsply Sirona, OsseospeedTM and Straumann SLActive, with mean follow-up times of 3.84 years (SE: 0.15) and 3.34 years (SE: 0.15), respectively. The surfaces have different topographies and surface chemistry. However, no significant association was found between PI and implant surface/system, including no difference in the onset or severity of the disease. Nonetheless, plaque control was associated with an increased risk of developing PI, along with the gender of the patient. Furthermore, patients suffering from PI exhibited increased BL in the anterior region. CONCLUSION: No differences were observed among the evaluated implant systems, although the surfaces have different topography and chemistry. Factors that affected the risk of developing PI were plaque index and male gender. The severity of BL in patients with PI was more pronounced in the anterior region. Consequently, our findings show that success in implantology is less contingent on selecting implant systems and more on a better understanding of patient-specific risk factors, as well as on implementing biomaterials that can more effectively debride dental implants.

The influence of copper-doped mesoporous bioactive nanospheres on the temperature rise during polymerization, polymer cross-linking density, monomer release and embryotoxicity of dental composites.

OBJECTIVES: Composites with copper-doped mesoporous bioactive nanospheres (Cu-MBGN) were developed to prevent secondary caries by imparting antimicrobial and ion-releasing/remineralizing properties. METHODS: Seven experimental composites containing 1, 5 or 10 wt% Cu-MBGN, the corresponding inert controls (silica) and bioactive controls (bioactive glass 45S5) were prepared. The temperature rise during light curing, cross-linking density by ethanol softening test, monomer elution and their potential adverse effects on the early development of zebrafish Danio rerio was investigated. RESULTS: Materials combining Cu-MBGN and silica showed the highest resistance to ethanol softening, as did the bioactive controls. Cu-MBGN composites showed significant temperature rise and reached maximum temperature in the shortest time. Bisphenol A was not detected, while bis-GMA was found only in the control materials and TEGDMA in the eluates of all materials. There was no increase in zebrafish mortality and abnormality rates during exposure to the eluates of any of the materials. CONCLUSIONS: The composite with 5 wt% Cu-MBGN combined with nanosilica fillers showed the lowest ethanol softening, indicating the polymer's highest durability and cross-linking density. Despite the TEGDMA released from all tested materials, no embryotoxic effect was observed.

Enhanced Bone Healing in Critical-Sized Rabbit Femoral Defects: Impact of Helical and Alternate Scaffold Architectures.

This study investigates the effect of scaffold architecture on bone regeneration, focusing on 3D-printed polylactic acid-bioceramic calcium phosphate (PLA-bioCaP) composite scaffolds in rabbit femoral condyle critical defects. We explored two distinct scaffold designs to assess their influence on bone healing and scaffold performance. Structures with alternate (0°/90°) and helical (0°/45°/90°/135°/180°) laydown patterns were manufactured with a 3D printer using a fused deposition modeling technique. The scaffolds were meticulously characterized for pore size, strut thickness, porosity, pore accessibility, and mechanical properties. The in vivo efficacy of these scaffolds was evaluated using a femoral condyle critical defect model in eight skeletally mature New Zealand White rabbits. Then, the results were analyzed micro-tomographically, histologically, and histomorphometrically. Our findings indicate that both scaffold architectures are biocompatible and support bone formation. The helical scaffolds, characterized by larger pore sizes and higher porosity, demonstrated significantly greater bone regeneration than the alternate structures. However, their lower mechanical strength presented limitations for use in load-bearing sites.

Biofouling on titanium implants: a novel formulation of poloxamer and peroxide for in situ removal of pellicle and multi-species oral biofilm.

Eradicating biofouling from implant surfaces is essential in treating peri-implant infections, as it directly addresses the microbial source for infection and inflammation around dental implants. This controlled laboratory study examines the effectiveness of the four commercially available debridement solutions '(EDTA (Prefgel®), NaOCl (Perisolv®), H2O2 (Sigma-Aldrich) and Chlorhexidine (GUM® Paroex®))' in removing the acquired pellicle, preventing pellicle re-formation and removing of a multi-species oral biofilm growing on a titanium implant surface, and compare the results with the effect of a novel formulation of a peroxide-activated 'Poloxamer gel (Nubone® Clean)'. Evaluation of pellicle removal and re-formation was conducted using scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy to assess the surface morphology, elemental composition and chemical surface composition. Hydrophilicity was assessed through contact angle measurements. The multi-species biofilm model included Streptococcus oralis, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans, reflecting the natural oral microbiome's complexity. Biofilm biomass was quantified using safranin staining, biofilm viability was evaluated using confocal laser scanning microscopy, and SEM was used for morphological analyses of the biofilm. Results indicated that while no single agent completely eradicated the biofilm, the 'Poloxamer gel' activated with 'H2O2' exhibited promising results. It minimized re-contamination of the pellicle by significantly lowering the contact angle, indicating enhanced hydrophilicity. This combination also showed a notable reduction in carbon contaminants, suggesting the effective removal of organic residues from the titanium surface, in addition to effectively reducing viable bacterial counts. In conclusion, the 'Poloxamer gel + H2O2' combination emerged as a promising chemical decontamination strategy for peri-implant diseases. It underlines the importance of tailoring treatment methods to the unique microbial challenges in peri-implant diseases and the necessity of combining chemical decontaminating strategies with established mechanical cleaning procedures for optimal management of peri-implant diseases.

Multiple choice as formative assessment in dental education.

INTRODUCTION: The effectiveness of multiple-choice questions (MCQs) in dental education is pivotal to student performance and knowledge advancement. However, their optimal implementation requires exploration to enhance the benefits. MATERIALS AND METHODS: An educational tool incorporating MCQs was administered from the 5th to the 10th semester in a dental curriculum. The students filled out a questionnaire after the MCQ, which was linked to the learning management system. Four cohorts of four semesters generated 2300 data points analysed by Spearmen correlation and mixed model regression analysis. RESULTS: Demonstrated a significant correlation between early exam preparation and improved student performance. Independent study hours and lecture attendance emerged as significant predictors, accounting for approximately 10.27% of the variance in student performance on MCQs. While the number of MCQs taken showed an inverse relationship with study hours, the perceived clarity of these questions positively correlated with academic achievement. CONCLUSION: MCQs have proven effective in enhancing student learning and knowledge within the discipline. Our analysis underscores the important role of independent study and consistent lecture attendance in positively influencing MCQ scores. The study provides valuable insights into using MCQs as a practical tool for dental student learning. Moreover, the clarity of assessment tools, such as MCQs, remains pivotal in influencing student outcomes. This study underscores the multifaceted nature of learning experiences in dental education and the importance of bridging the gap between student expectations and actual performance.

Towards bone regeneration: Understanding the nucleating ability of proline-rich peptides in biomineralisation.

Obtaining rapid mineralisation is a challenge in current bone graft materials, which has been attributed to the difficulty of guiding the biological processes towards osteogenesis. Amelogenin, a key protein in enamel formation, inspired the design of two intrinsically disordered peptides (P2 and P6) that enhance in vivo bone formation, but the process is not fully understood. In this study, we have elucidated the mechanism by which these peptides induce improved mineralisation. Our molecular dynamics analysis demonstrated that in an aqueous environment, P2 and P6 fold to interact with the surrounding Ca2+, PO43- and OH- ions, which can lead to apatite nucleation. Although P2 has a less stable backbone, it folds to a stable structure that allows for the nucleation of larger calcium phosphate aggregates than P6. These results were validated experimentally in a concentrated simulated body fluid solution, where the peptide solutions accelerated the mineralisation process compared to the control and yielded mineral structures mimicking the amorphous calcium phosphate crystals that can be found in lamella bone. A pH drop for the peptide groups suggests depletion of calcium and phosphate, a prerequisite for intrinsic osteoinduction, while S/TEM and SEM suggested that the peptide regulated the mineral nucleation into lamella flakes. Evidently, the peptides accelerate and guide mineral formation, elucidating the mechanism for how these peptides can improve the efficacy of P2 or P6 containing devices for bone regeneration. The work also demonstrates how experimental mineralisation study coupled with molecular dynamics is a valid method for understanding and predicting in vivo performance prior to animal trials.

From Basic Science to Clinical Practice: A Review of Current Periodontal/Mucogingival Regenerative Biomaterials.

Periodontitis is a dysbiosis-driven inflammatory disease affecting the tooth-supporting tissues, characterized by their progressive resorption, which can ultimately lead to tooth loss. A step-wise therapeutic approach is employed for periodontitis. After an initial behavioral and non-surgical phase, intra-bony or furcation defects may be amenable to regenerative procedures. This review discusses the regenerative technologies employed for periodontal regeneration, highlighting the current limitations and future research areas. The search, performed on the MEDLINE database, has identified the available biomaterials, including biologicals (autologous platelet concentrates, hydrogels), bone grafts (pure or putty), and membranes. Biologicals and bone grafts have been critically analyzed in terms of composition, mechanism of action, and clinical applications. Although a certain degree of periodontal regeneration is predictable in intra-bony and class II furcation defects, complete defect closure is hardly achieved. Moreover, treating class III furcation defects remains challenging. The key properties required for functional regeneration are discussed, and none of the commercially available biomaterials possess all the ideal characteristics. Therefore, research is needed to promote the advancement of more effective and targeted regenerative therapies for periodontitis. Lastly, improving the design and reporting of clinical studies is suggested by strictly adhering to the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement.

Contrast-enhanced Micro-CT 3D visualization of cell distribution in hydrated human cornea.

Background: The cornea, a vital component of the human eye, plays a crucial role in maintaining visual clarity. Understanding its ultrastructural organization and cell distribution is fundamental for elucidating corneal physiology and pathology. This study comprehensively examines the microarchitecture of the hydrated human cornea using contrast-enhanced micro-computed tomography (micro-CT). Method: Fresh human corneal specimens were carefully prepared and hydrated to mimic their in vivo state. Contrast enhancement with Lugol's iodine-enabled high-resolution Micro-CT imaging. The cells' three-dimensional (3D) distribution within the cornea was reconstructed and analyzed. Results: The micro-CT imaging revealed exquisite details of the corneal ultrastructure, including the spatial arrangement of cells throughout its depth. This novel approach allowed for the visualization of cells' density and distribution in different corneal layers. Notably, our findings highlighted variations in cell distribution between non-hydrated and hydrated corneas. Conclusions: This study demonstrates the potential of contrast-enhanced micro-CT as a valuable tool for non-destructive, 3D visualization and quantitative analysis of cell distribution in hydrated human corneas. These insights contribute to a better understanding of corneal physiology and may have implications for research in corneal diseases and tissue engineering.

Redefining biomaterial biocompatibility: challenges for artificial intelligence and text mining.

The surge in 'Big data' has significantly influenced biomaterials research and development, with vast data volumes emerging from clinical trials, scientific literature, electronic health records, and other sources. Biocompatibility is essential in developing safe medical devices and biomaterials to perform as intended without provoking adverse reactions. Therefore, establishing an artificial intelligence (AI)-driven biocompatibility definition has become decisive for automating data extraction and profiling safety effectiveness. This definition should both reflect the attributes related to biocompatibility and be compatible with computational data-mining methods. Here, we discuss the need for a comprehensive and contemporary definition of biocompatibility and the challenges in developing one. We also identify the key elements that comprise biocompatibility, and propose an integrated biocompatibility definition that enables data-mining approaches.

Biocompatible Nanostructured Silver-Incorporated Implant Surfaces Show Effective Antibacterial, Osteogenic, and Anti-Inflammatory Effects in vitro and in Rat Model.

Introduction: Titanium (Ti) and its alloys are widely utilized in endosseous implants. However, their clinical efficacy is marred by complications arising from bacterial infections owing to their inadequate antibacterial properties. Consequently, enhancing the antibacterial attributes of implant surfaces stands as a pivotal objective in the realm of implantable materials research. Methods: In this study, we employed sequential anodization and plasma immersion ion implantation (PIII) technology to fabricate a silver-embedded sparsely titania nanotube array (SNT) on the near-ß titanium alloy Ti-5Zr-3Sn-5Mo-15Nb (TLM) implants. The surface characteristics, antimicrobial properties, biocompatibility, and osteogenic activity of the silver-nanomodified SNT implant (SNT Ag) surface, alongside peri-implant inflammatory responses, were meticulously assessed through a combination of in vitro and in vivo analyses. Results: Compared with polished TLM and SNT, the silver-embedded SNT (SNT Ag) surface retained the basic shape of nanotubes and stably released Ag+ at the ppm level for a long time, which demonstrated an effective inhibition and bactericidal activity against Staphylococcus aureus (SA) while maintaining ideal cytocompatibility. Additionally, the subtle modifications in nanotubular topography induced by silver implantation endowed SNT Ag with enhanced osteogenic activity and mitigated inflammatory capsulation in soft tissue peri-implants in a rat model. Conclusion: Incorporating a silver-embedded SNT array onto the implant surface demonstrated robust antibacterial properties, impeccable cytocompatibility, exceptional osteogenic activity, and the potential to prevent inflammatory encapsulation around the implant site. The Silver-PIII modification strategy emerges as a highly promising approach for surface applications in endosseous implants and trans-gingival implant abutments.

Photoannealing of Microtissues Creates High-Density Capillary Network Containing Living Matter in a Volumetric-Independent Manner.

The vascular tree is crucial for the survival and function of large living tissues. Despite breakthroughs in 3D bioprinting to endow engineered tissues with large blood vessels, there is currently no approach to engineer high-density capillary networks into living tissues in a scalable manner. Here, photoannealing of living microtissue (PALM) is presented as a scalable strategy to engineer capillary-rich tissues. Specifically, in-air microfluidics is used to produce living microtissues composed of cell-laden microgels in ultrahigh throughput, which can be photoannealed into a monolithic living matter. Annealed microtissues inherently give rise to an open and interconnected pore network within the resulting living matter. Interestingly, utilizing soft microgels enables microgel deformation, which leads to the uniform formation of capillary-sized pores. Importantly, the ultrahigh throughput nature underlying the microtissue formation uniquely facilitates scalable production of living tissues of clinically relevant sizes (>1 cm3 ) with an integrated high-density capillary network. In short, PALM generates monolithic, microporous, modular tissues that meet the previously unsolved need for large engineered tissues containing high-density vascular networks, which is anticipated to advance the fields of engineered organs, regenerative medicine, and drug screening.

Morphometric micro-CT study of contralateral mandibular incisors.

OBJECTIVES: This study aimed to determine the degree of similarity and symmetry in the anatomy of contralateral mandibular incisors. Three-dimensional (3D) models of extracted teeth were obtained from microtomography (micro-CT) scans. Qualitative and quantitative assessments of the morphology and comparison of contralateral pairs were made. The null hypothesis was that contralateral mandibular incisors could not be considered identical in simple morphometric measurements. METHODS: Sixty pairs of mandibular incisors were extracted from 30 patients and scanned with micro-CT. Virtual models of the cemento-enamel junction to the root apex were rendered. Parameters such as length, canal width, dentinal thicknesses, tortuosity, centerline length, accessory canals, root canal configurations, and root canal orifice cross-sections were used to compare the teeth. Width and thickness comparisons between paired teeth in the same individual were made by paired t-test (Wilcoxon signed-rank test for variables not normally distributed). An online randomization tool generated randomized pairs (independent of the individual/patient). Subsequently, an unpaired t-test (or Mann-Whitney U test for non-normally distributed parameters) and a correlation analysis were conducted. Canal configurations were classified according to preexisting classification schemes. The number and location of accessory canals and apical foramina were registered and compared. RESULTS: Utilizing advanced imaging techniques and quantitative analyses, our study establishes that contralateral mandibular incisors exhibit a remarkable degree of symmetry in multiple morphological parameters, including length, canal width, and dentinal thicknesses. The apical third showed a high degree of inter-variability for the contralateral pairs. The rigorous statistical analysis of the normalized parameters by Z-score showed no statistically significant differences between the contralateral mandibular incisors. Comparisons between central and lateral teeth revealed differences in root length but no significant disparity in the distribution of accessory canals. Central teeth, on average, were longer, while accessory canals were distributed relatively evenly between central and lateral teeth. CONCLUSIONS: The findings of this study further establish the significant similarities between contralateral mandibular incisors, reinforcing their suitability as a reliable substrate for root canal comparison studies. CLINICAL RELEVANCE: The absence of statistically significant differences between contralateral pairs in normalized parameters underscores their potential as a reliable reference point for root canal comparison studies in clinical dentistry. Furthermore, our findings emphasize the importance of individualized treatment planning, considering the natural symmetry in mandibular incisors to enhance clinical decision-making. This research contributes valuable insights to the field of endodontics, offering a standardized approach to sample selection and enriching the understanding of dental anatomy.

Adipose-Derived Stromal Cells Preserve Pancreatic Islet Function in a Transplantable 3D Bioprinted Scaffold.

Intra-portal islet transplantation is currently the only clinically approved beta cell replacement therapy, but its outcome is hindered by limited cell survival due to a multifactorial reaction against the allogeneic tissue in liver. Adipose-derived stromal cells (ASCs) can potentially improve the islet micro-environment by their immunomodulatory action. The challenge is to combine both islets and ASCs in a relatively easy and consistent long-term manner in a deliverable scaffold. Manufacturing the 3D bioprinted double-layered scaffolds with primary islets and ASCs using a mix of alginate/nanofibrillated cellulose (NFC) bioink is reported. The diffusion properties of the bioink and the supportive effect of human ASCs on islet viability, glucose sensing, insulin secretion, and reducing the secretion of pro-inflammatory cytokines are demonstrated. Diabetic mice transplanted with islet-ASC scaffolds reach normoglycemia seven days post-transplantation with no significant difference between this group and the group received islets under the kidney capsules. In addition, animals transplanted with islet-ASC scaffolds stay normoglycemic and show elevated levels of C-peptide compared to mice transplanted with islet-only scaffolds. The data present a functional 3D bioprinted scaffold for islets and ASCs transplanted to the extrahepatic site and suggest a possible role of ASCs on improving the islet micro-environment.

Durability assessment of hydrogel mountings for contrast-enhanced micro-CT.

Micro-computed tomography (micro-CT) provides valuable data for studying soft tissue, though it is often affected by sample movement during scans and low contrast in X-ray absorption. This can result in lower image quality and geometric inaccuracies, collectively known as 'artefacts'. To mitigate these issues, samples can be embedded in hydrogels and enriched with heavy metals for contrast enhancement. However, the long-term durability of these enhancements remains largely unexplored. In this study, we examine the effects of two contrast enhancement agents - iodine and phosphotungstic acid (PTA) - and two hydrogels - agarose and Poloxamer 407 - over a 14-day period. We used Drosophila melanogaster as a test model for our investigation. Our findings reveal that PTA and agarose are highly durable, while iodine and poloxamer hydrogel exhibits higher leakage rates. These observations lay the foundation for estimating contrast stabilities in contrast-enhanced micro-CT with hydrogel embedding and serve to inform future research in this field.

Osteocyte-Like Cells Differentiated From Primary Osteoblasts in an Artificial Human Bone Tissue Model.

In vitro models of primary human osteocytes embedded in natural mineralized matrix without artificial scaffolds are lacking. We have established cell culture conditions that favored the natural 3D orientation of the bone cells and stimulated the cascade of signaling needed for primary human osteoblasts to differentiate into osteocytes with the characteristically phenotypical dendritic network between cells. Primary human osteoblasts cultured in a 3D rotating bioreactor and incubated with a combination of vitamins A, C, and D for up to 21 days produced osteospheres resembling native bone. Osteocyte-like cells were identified as entrapped, stellate-shaped cells interconnected through canaliculi embedded in a structured, mineralized, collagen matrix. These cells expressed late osteoblast and osteocyte markers such as osteocalcin (OCN), podoplanin (E11), dentin matrix acidic phosphoprotein 1 (DMP1), and sclerostin (SOST). Organized collagen fibrils, observed associated with the cell hydroxyapatite (HAp) crystals, were found throughout the spheroid and in between the collagen fibrils. In addition to osteocyte-like cells, the spheroids consisted of osteoblasts at various differentiation stages surrounded by a rim of cells resembling lining cells. This resemblance to native bone indicates a model system with potential for studying osteocyte-like cell differentiation, cross-talk between bone cells, and the mineralization process in a bonelike structure in vitro without artificial scaffolds. In addition, natural extracellular matrix may allow for the study of tissue-specific biochemical, biophysical, and mechanical properties. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

A Comparative Investigation of Chemical Decontamination Methods for In-Situ Cleaning of Dental Implant Surfaces.

Surface chemistry evaluation is crucial in assessing the efficacy of chemical decontamination products for titanium implants. This study aimed to investigate the effectiveness of chemical decontamination solutions in cleaning a contaminated dental implant surface and to evaluate the potential of combining Pluronic gel with hydrogen peroxide (NuBone®Clean) by evaluating pellicle disruption and re-formation on implant surfaces. In addition, ensuring safety with in vitro and human testing protocols. X-ray Photoelectron Spectroscopy (XPS) was utilised for surface analysis. All the tested gels had some effect on the surface cleanness except for PrefGel®. Among the tested chemical decontamination candidates, NuBone®Clean demonstrated effectiveness in providing a cleaner titanium surface. Furthermore, none of the tested chemical agents exhibited cytotoxic effects, and the safety assessment showed no adverse events. The results of this study highlight the significance of conducting comprehensive evaluations, encompassing safety and efficacy, before introducing new chemical agents for dental treatments. The findings suggest that NuBone®Clean shows potential as a chemical decontamination solution for implant surfaces. However, further investigation through randomised clinical trials is necessary. By adhering to rigorous testing protocols, the development of safe and efficient chemical decontamination strategies can be advanced, benefiting patients and promoting progress in implant dentistry.

Fatigue behaviour of a self-healing dental composite.

OBJECTIVE: Novel self-healing resin-based composites containing microcapsules have been developed to improve the mechanical performance of dental restorations. However, the long-term fatigue behaviour of these self-healing composites has still been hardly investigated. Therefore, this manuscript studied the fatigue behaviour of self-healing composites containing microcapsules by subjecting the specimens to traditional staircase tests and ageing in a custom-designed chewing simulator (Rub&Roll) to simulate oral ageing physiologically relevant conditions. METHODS: To prepare self-healing composite, poly(urea-formaldehyde) microcapsules containing acrylic self-healing liquids were synthesized. Subsequently, these microcapsules (10 wt%) and initiator (benzoyl peroxide, BPO, 2 wt%) were incorporated into a commercial flowable resin-based composite. Microcapsule-free resin-based composites with and without BPO were also prepared as control specimens. A three-point flexural test was used to measure the initial flexural strength (Sinitial). Subsequently, half of the specimens were used for fatigue testing using a common staircase approach to measure the fatigue strengths (FS). In addition, the other specimens were aged in the Rub&Roll machine for four weeks where after the final flexural strength (Sfinal) was measured. RESULTS: Compared to Sinitial, FS of all tested specimens significantly decreased as measured through staircase testing. After 4 weeks of ageing in the Rub&Roll machine, Sfinal was significantly reduced compared to Sinitial for microcapsule-free resin-based composites, but not for the self-healing composites (p = 0.3658). However, the self-healing composites are still in the experimental phase characterized by a low mechanical strength, which still impedes further clinical translation. SIGNIFICANCE: Self-healing composites containing microcapsules exhibit improved fatigue resistance compared to microcapsule-free non-self-healing composites.

ß-Cyclodextrin functionalized agarose-based hydrogels for multiple controlled drug delivery of ibuprofen.

Agarose hydrogels are three-dimensional hydrophilic polymeric frameworks characterised by high water content, viscoelastic properties, and excellent ability as cell and drug delivery systems. However, their hydrophilicity as gel systems makes loading of hydrophobic drugs difficult and often ineffective. The incorporation of amphiphilic molecules (e.g. cyclodextrins) into hydrogels as hosts able to form inclusion complexes with hydrophobic drugs could be a possible solution. However, if not properly confined, the host compounds can get out of the network resulting in uncontrolled release. Therefore, in this work, ß-cyclodextrins-based host-guest supramolecular hydrogel systems were synthesised, with ß-cyclodextrins (ß-CD) covalently bound to the polymeric network, preventing leakage of the host molecules. Hydrogels were prepared at two different ß-CD-functionalized polyvinyl alcohol (PVA)/agarose ratios, and characterised chemically and physically. Then ibuprofen, a drug often used as a gold standard in studies involving ß-CD both in its hydrophilic and hydrophobic forms, was selected to investigate the release behavior of the synthesised hydrogels and the influence of ß-CD on the release. The presence of ß-CD linked to the polymeric 3D network ensured a higher and prolonged release profile for the hydrophobic drug and also seemed to have some influence on the hydrophilic one.

Use of 3D-printed polylactic acid/bioceramic composite scaffolds for bone tissue engineering in preclinical in vivo studies: A systematic review.

3D-printed composite scaffolds have emerged as an alternative to deal with existing limitations when facing bone reconstruction. The aim of the study was to systematically review the feasibility of using PLA/bioceramic composite scaffolds manufactured by 3D-printing technologies as bone grafting materials in preclinical in vivo studies. Electronic databases were searched using specific search terms, and thirteen manuscripts were selected after screening. The synthesis of the scaffolds was carried out using mainly extrusion-based techniques. Likewise, hydroxyapatite was the most used bioceramic for synthesizing composites with a PLA matrix. Among the selected studies, seven were conducted in rats and six in rabbits, but the high variability that exists regarding the experimental process made it difficult to compare them. Regarding the results, PLA/Bioceramic composite scaffolds have shown to be biocompatible and mechanically resistant. Preclinical studies elucidated the ability of the scaffolds to be used as bone grafts, allowing bone growing without adverse reactions. In conclusion, PLA/Bioceramics scaffolds have been demonstrated to be a promising alternative for treating bone defects. Nevertheless, more care should be taken when designing and performing in vivo trials, since the lack of standardization of the processes, which prevents the comparison of the results and reduces the quality of the information. STATEMENT OF SIGNIFICANCE: 3D-printed polylactic acid/bioceramic composite scaffolds have emerged as an alternative to deal with existing limitations when facing bone reconstruction. Since preclinical in vivo studies with animal models represent a mandatory step for clinical translation, the present manuscript analyzed and discussed not only those aspects related to the selection of the bioceramic material, the synthesis of the implants and their characterization. But provides a new approach to understand how the design and perform of clinical trials, as well as the selection of the analysis methods, may affect the obtained results, by covering authors' knowledgebase from veterinary medicine to biomaterial science. Thus, this study aims to systematically review the feasibility of using polylactic acid/bioceramic scaffolds as grafting materials in preclinical trials.

Hard and soft tissue healing around teeth prepared with the biologically oriented preparation technique and restored with provisional crowns: An in vivo experimental investigation.

AIM: To evaluate the hard and soft tissues healing around teeth prepared with the biologically oriented preparation technique (BOPT) versus the chamfer technique versus non-prepared teeth. MATERIALS AND METHODS: Thirty-two teeth in eight beagle dogs were randomly prepared with the BOPT (test = 16) or chamfer (control = 16) techniques and covered with polymethylmethacrylate crowns as provisional restorations. Sixteen negative controls (non-prepared teeth) were also used for comparison. Histological description and histomorphometrical measurements of the periodontal tissues were collected at 4 and 12 weeks in 7 out of 8 dogs, including the soft tissue height and thickness, and the horizontal and vertical bone dimensions. RESULTS: When compared with negative controls, test and control preparation techniques exhibited a more apical location of the free gingival margin with respect to the cement-enamel junction (∆ = 1.1 mm for both groups at 4 weeks (p < .05), 0.99 mm for the test group (p = .043) and 0.20 mm for control group (p = 1.000) at 12 weeks). There were no significant differences between test and control groups with respect to vertical and horizontal histometric measurements. CONCLUSIONS: The BOPT and chamfer tooth preparation protocols induced similar qualitative and quantitative changes in the healing of the supra-crestal soft tissue complex, when compared with non-prepared teeth. Despite the limited amount of power, it appeared that differences between the tested preparation techniques were not statistically significant.