Primary stability evaluation of different morse cone implants in low-density artificial bone blocks: A comparison between high-and low-speed drilling.

This study aimed to evaluate various biomechanical parameters associated with the primary stability of Maestro and Due Cone implants placed in low-density artificial bones, prepared using high-speed drilling with irrigation and low-speed drilling without irrigation. The insertion torque (IT), removal torque (RT), and implant stability quotient (ISQ) values were recorded for Maestro and Due Cone implants placed in low-density polyurethane blocks (10 and 20 pounds per cubic foot (PCF) with and without a cortical layer) prepared using high-speed and low-speed with or without irrigation using a saline solution, respectively. A three-way ANOVA model and Tukey's post-hoc test were conducted, presenting data as means and standard deviations. P-values equal to or less than 0.05 were considered statistically significant. No statistically significant differences in IT, RT, and ISQ between drilling speeds were observed. However, Maestro implants exhibited lower IT and RT values after high- and low-speed drilling across almost all polyurethane blocks, significantly evident in the 20 PCF density block for IT and in the 20 PCF density block with the cortical layer for the RT with low-speed drilling (IT: 47.33 ± 10.02 Ncm and 16.00 ± 12.49 Ncm for Due Cone and Maestro implants, respectively, with p < 0.01; RT: 44.67 ± 22.81 Ncm and 20.01 ± 4.36 Ncm for Due Cone and Maestro implants, respectively, with p < 0.05) and among the same implant types inserted in different bone densities. Additionally, the study found that for all bone densities and drilling speeds, both implants registered ISQ values exceeding 60, except for the lowest-density polyurethane block. Overall, it can be inferred that low-speed drilling without irrigation achieved biomechanical parameters similar to conventional drilling with both implant types, even with lower IT values in the case of Maestro implants. These findings suggest a promising potential use of low-speed drilling without irrigation in specific clinical scenarios, particularly when focusing on preparation depth or when ensuring proper irrigation is challenging.

The Incorporation of Zinc into Hydroxyapatite and Its Influence on the Cellular Response to Biomaterials: A Systematic Review.

Zinc is known for its role in enhancing bone metabolism, cell proliferation, and tissue regeneration. Several studies proposed the incorporation of zinc into hydroxyapatite (HA) to produce biomaterials (ZnHA) that stimulate and accelerate bone healing. This systematic review aimed to understand the physicochemical characteristics of zinc-doped HA-based biomaterials and the evidence of their biological effects on osteoblastic cells. A comprehensive literature search was conducted from 2022 to 2024, covering all years of publications, in three databases (Web of Science, PUBMED, Scopus), retrieving 609 entries, with 36 articles included in the analysis according to the selection criteria. The selected studies provided data on the material's physicochemical properties, the methods of zinc incorporation, and the biological effects of ZnHA on bone cells. The production of ZnHA typically involves the wet chemical synthesis of HA and ZnHA precursors, followed by deposition on substrates using processes such as liquid precursor plasma spraying (LPPS). Characterization techniques confirmed the successful incorporation of zinc into the HA lattice. The findings indicated that zinc incorporation into HA at low concentrations is non-cytotoxic and beneficial for bone cells. ZnHA was found to stimulate cell proliferation, adhesion, and the production of osteogenic factors, thereby promoting in vitro mineralization. However, the optimal zinc concentration for the desired effects varied across studies, making it challenging to establish a standardized concentration. ZnHA materials are biocompatible and enhance osteoblast proliferation and differentiation. However, the mechanisms of zinc release and the ideal concentrations for optimal tissue regeneration require further investigation. Standardizing these parameters is essential for the effective clinical application of ZnHA.

The Influence of Cement Thickness within the Cap on Stress Distribution for Dental Implants.

The purpose of this finite element analysis (FEA) was to evaluate the stress distribution within the prosthetic components and bone in relation to varying cement thicknesses (from 20 to 60 µm) utilized to attach a zirconia crown on a conometric cap. The study focused on two types of implants (Cyroth and TAC, AoN Implants, Grisignano di Zocco, Italy) featuring a Morse cone connection. Detailed three-dimensional (3D) models were developed to represent the bone structure (cortical and trabecular) and the prosthetic components, including the crown, cement, cap, abutment, and the implant. Both implants were placed 1.5 mm subcrestally and subjected to a 200 N load at a 45° inclination on the crown. The results indicated that an increase in cement thickness led to a reduction in von Mises stress on the cortical bone for both Cyroth and TAC implants, while the decrease in stress on the trabecular bone (apical zone) was relatively less pronounced. However, the TAC implant exhibited a higher stress field in the apical area compared to the Cyroth implant. In summary, this study investigated the influence of cement thickness on stress transmission across prosthetic components and peri-implant tissues through FEA analysis, emphasizing that the 60 µm cement layer demonstrated higher stress values approaching the material strength limit.

Assessment of Pyrogenic Response of Medical Devices and Biomaterials by the Monocyte Activation Test (MAT): A Systematic Review.

Pyrogens are fever-inducing substances routinely investigated in health products through tests such as the Rabbit Pyrogen Test (RPT), the Limulus Amebocyte Lysate (LAL), and the Monocyte Activation Test (MAT). However, the applications of the MAT for medical devices and biomaterials remain limited. This work aimed to overview the studies evaluating the pyrogenicity of medical devices and biomaterials using the MAT, highlighting its successes and potential challenges. An electronic search was performed by December 2023 in PubMed, Scopus, and Web of Science, identifying 321 records which resulted in ten selected studies. Data were extracted detailing the tested materials, MAT variants, interferences, and comparisons between methods. Methodological quality was assessed using the ToxRTool, and the results were synthesized descriptively. The selected studies investigated various materials, including polymers, metals, and natural compounds, employing the different biological matrices of the MAT. Results showed the MAT's versatility, with successful detection of pyrogens in most materials tested, though variability in sensitivity was noted based on the material and testing conditions. Challenges remain in optimizing protocols for different material properties, such as determining the best methods for direct contact versus eluate testing and addressing the incubation conditions. In conclusion, the MAT demonstrates significant potential as a pyrogen detection method for medical devices and biomaterials. However, continued research is essential to address existing gaps, optimize protocols, and validate the test across a broader range of materials.

Exosome-like Systems: From Therapies to Vaccination for Cancer Treatment and Prevention-Exploring the State of the Art.

Cancer remains one of the main causes of death in the world due to its increasing incidence and treatment difficulties. Although significant progress has been made in this field, innovative approaches are needed to reduce tumor incidence, progression, and spread. In particular, the development of cancer vaccines is currently ongoing as both a preventive and therapeutic strategy. This concept is not new, but few vaccines have been approved in oncology. Antigen-based vaccination emerges as a promising strategy, leveraging specific tumor antigens to activate the immune system response. However, challenges persist in finding suitable delivery systems and antigen preparation methods. Exosomes (EXs) are highly heterogeneous bilayer vesicles that carry several molecule types in the extracellular space. The peculiarity is that they may be released from different cells and may be able to induce direct or indirect stimulation of the immune system. In particular, EX-based vaccines may cause an anti-tumor immune attack or produce memory cells recognizing cancer antigens and inhibiting disease development. This review delves into EX composition, biogenesis, and immune-modulating properties, exploring their role as a tool for prevention and therapy in solid tumors. Finally, we describe future research directions to optimize vaccine efficacy and realize the full potential of EX-based cancer immunotherapy.

The influence of truncated-conical implant length on primary stability in maxillary and mandibular regions: an in vitro study using polyurethane blocks.

OBJECTIVES: This in vitro study is aimed at assessing whether implant primary stability is influenced by implant length in artificial bone with varying densities. MATERIALS AND METHODS: A total of 120 truncated-conical implants (60 long-length: 3p L, 3.8 × 14 mm; 60 short-length: 3p S, 3.8 × 8 mm) were inserted into 20, 30, and 40 pounds per cubic foot (PCF) density polyurethane blocks. The insertion torque (IT), removal torque (RT), and resonance frequency analysis (RFA) values were recorded for each experimental condition. RESULTS: In 30 and 40 PCF blocks, 3p S implants exhibited significantly higher IT values (90 and 80 Ncm, respectively) than 3p L (85 and 50 Ncm, respectively). Similarly, RT was significantly higher for 3p S implants in 30 and 40 PCF blocks (57 and 90 Ncm, respectively). However, there were no significant differences in RFA values, except for the 20 PCF block, where 3pS implants showed significantly lower values (63 ISQ) than 3p L implants (67 ISQ) in both the distal and mesial directions. CONCLUSIONS: These results demonstrated that the implant's length mainly influences the IT and RT values in the polyurethane blocks that mimic the mandibular region of the bone, resulting in higher values for the 3p S implants, while the RFA values remained unaffected. However, in the lowest density block simulating the maxillary bone, 3p L implants exhibited significantly higher ISQ values. CLINICAL RELEVANCE: Therefore, our data offer valuable insights into the biomechanical behavior of these implants, which could be clinically beneficial for enhancing surgical planning.

Crestal and Subcrestal Placement of Morse Cone Implant-Abutment Connection Implants: An In Vitro Finite Element Analysis (FEA) Study.

The issue of dental implant placement relative to the alveolar crest, whether in supracrestal, equicrestal, or subcrestal positions, remains highly controversial, leading to conflicting data in various studies. Three-dimensional (3D) Finite Element Analysis (FEA) can offer insights into the biomechanical aspects of dental implants and the surrounding bone. A 3D model of the jaw was generated using computed tomography (CT) scans, considering a cortical thickness of 1.5 mm. Subsequently, Morse cone implant-abutment connection implants were virtually positioned at the model's center, at equicrestal (0 mm) and subcrestal levels (-1 mm and -2 mm). The findings indicated the highest stress within the cortical bone around the equicrestally placed implant, the lowest stress in the -2 mm subcrestally placed implant, and intermediate stresses in the -1 mm subcrestally placed implant. In terms of clinical relevance, this study suggested that subcrestal placement of a Morse cone implant-abutment connection (ranging between -1 and -2 mm) could be recommended to reduce peri-implant bone resorption and achieve longer-term implant success.

Electron Microscopy (EM) Analysis of Collagen Fibers in the Peri-Implant Soft Tissues around Two Different Abutments.

The design of the implant prosthesis-abutment complex appears crucial for shaping healthy and stable peri-implant soft tissues. The aim of the present animal study was to compare two implants with different healing abutment geometries: a concave design (TEST) and a straight one (CTRL). Transmission electron microscopy (TEM) was used to quantify the three-dimensional topography and morphological properties of collagen at nanoscale resolution. 2 swine were included in the experiment and 6 implants per animal were randomly placed in the left or right hemimandible in either the physiologically mature bone present between the lower canine and first premolar or in the mandibular premolar area, within tooth extraction sites. Each CTRL implant was positioned across from its respective TEST implant on the other side of the jaw. After 12 weeks of healing, 8 specimens (4 CTRL and 4 TEST) were retrieved and prepared for histological and TEM analysis. The results showed a significantly higher percentage of area covered by collagen bundles and average bundle size in TEST implants, as well as a significant decrease in the number of longitudinally oriented bundles with respect to CTRL implants, which is potentially due to the larger size of TEST bundles. These data suggest that a concave transmucosal abutment design serves as a scaffold, favoring the deposition and growth of a well-organized peri-implant collagen structure over the implant platform in the early healing phase, also promoting the convergence of collagen fibers toward the abutment collar.

Finite Element Analysis (FEA) of a Premaxillary Device: A New Type of Subperiosteal Implant to Treat Severe Atrophy of the Maxilla.

Extreme atrophy of the maxilla still poses challenges for clinicians. Some of the techniques used to address this issue can be complex, risky, expensive, and time consuming, often requiring skilled surgeons. While many commonly used techniques have achieved very high success rates, complications may arise in certain cases. In this context, the premaxillary device (PD) technique offers a simpler approach to reconstruct severely atrophic maxillae, aiming to avoid more complicated and risky surgical procedures. Finite element analysis (FEA) enables the evaluation of different aspects of dental implant biomechanics. Our results demonstrated that using a PD allows for an optimal distribution of stresses on the basal bone, avoiding tension peaks that can lead to bone resorption or implant failure. ANSYS® was used to perform localized finite element analysis (FEA), enabling a more precise examination of the peri-crestal area and the PD through an accurate mesh element reconstruction, which facilitated the mathematical solution of FEA. The most favorable biomechanical behavior was observed for materials such as titanium alloys, which helped to reduce stress levels on bone, implants, screws, and abutments. Additionally, stress values remained within the limits of basal bone and titanium alloy strengths. In conclusion, from a biomechanical point of view, PDs appear to be viable alternatives for rehabilitating severe atrophic maxillae.

A Comparison of Conical and Cylindrical Implants Inserted in an In Vitro Post-Extraction Model Using Low-Density Polyurethane Foam Blocks.

Combining tooth extraction and implant placement reduces the number of surgical procedures that a patient must undergo. Thus, the present study aimed to compare the stability of two types of conical implants (TAC and INTRALOCK) and another cylindrical one (CYROTH), inserted with a range of angulation of 15-20 degrees in low-density polyurethane blocks (10 and 20 pounds per cubic foot, PCF) with or without a cortical lamina (30 PCF), which potentially mimicked the post-extraction in vivo condition. For this purpose, a total of 120 polyurethane sites were prepared (10 for each implant and condition) and the Insertion Torque (IT), Removal Torque (RT), and Resonance Frequency Analysis (RFA) were measured, following a Three-Way analysis of variance followed by Tukey's post hoc test for the statistical analysis of data. The IT and RT values registered for all implant types were directly proportional to the polyurethane density. The highest IT was registered by INTRALOCK implants in the highest-density block (32.44 ± 3.28 Ncm). In contrast, the highest RFA, a well-known index of Implant Stability Quotient (ISQ), was shown by TAC implants in all clinical situations (up to 63 ISQ in the 20 PCF block without the cortical sheet), especially in lower-density blocks. Although more pre-clinical and clinical studies are required, these results show a better primary stability of TAC conical implants in all tested densities of this post-extraction model, with a higher ISQ, despite their IT.

Essential Oils from Mediterranean Plants Inhibit In Vitro Monocyte Adhesion to Endothelial Cells from Umbilical Cords of Females with Gestational Diabetes Mellitus.

Essential oils (EOs) are mixtures of volatile compounds belonging to several chemical classes derived from aromatic plants using different distillation techniques. Recent studies suggest that the consumption of Mediterranean plants, such as anise and laurel, contributes to improving the lipid and glycemic profile of patients with diabetes mellitus (DM). Hence, the aim of the present study was to investigate the potential anti-inflammatory effect of anise and laurel EOs (AEO and LEO) on endothelial cells isolated from the umbilical cord vein of females with gestational diabetes mellitus (GDM-HUVEC), which is a suitable in vitro model to reproduce the pro-inflammatory phenotype of a diabetic endothelium. For this purpose, the Gas Chromatographic/Mass Spectrometric (GC-MS) chemical profiles of AEO and LEO were first analyzed. Thus, GDM-HUVEC and related controls (C-HUVEC) were pre-treated for 24 h with AEO and LEO at 0.025% v/v, a concentration chosen among others (cell viability by MTT assay), and then stimulated with TNF-α (1 ng/mL). From the GC-MS analysis, trans-anethole (88.5%) and 1,8-cineole (53.9%) resulted as the major components of AEO and LEO, respectively. The results in C- and GDM-HUVEC showed that the treatment with both EOs significantly reduced: (i) the adhesion of the U937 monocyte to HUVEC; (ii) vascular adhesion molecule-1 (VCAM-1) protein and gene expression; (iii) Nuclear Factor-kappa B (NF-κB) p65 nuclear translocation. Taken together, these data suggest the anti-inflammatory efficacy of AEO and LEO in our in vitro model and lay the groundwork for further preclinical and clinical studies to study their potential use as supplements to mitigate vascular endothelial dysfunction associated with DM.

Morpho-Functional Effect of a New Collagen-Based Medical Device on Human Gingival Fibroblasts: An In Vitro Study.

Maintaining periodontal and peri-implant soft tissues health is crucial for the long-term health of teeth and dental implants. New biomedical strategies aimed at avoiding connective tissue alterations and related diseases (e.g., periodontitis and peri-implantitis) are constantly evolving. Among these, collagen-based medical products have proven to be safe and effective. Accordingly, the aim of the present study was to evaluate the effects of Dental SKIN BioRegulation (Guna S.p.a., Milan, Italy), a new injectable medical device composed of type I collagen of porcine origin, on primary cultures of human gingival fibroblasts (hGF). To this end, hGF were cultured on collagen-coated (COL, 100 µg/2 mL) or uncoated plates (CTRL) before evaluating cell viability (24 h, 48 h, 72 h, and 7 d), wound healing properties (3 h, 6 h, 12 h, 24 h, and 48 h), and the activation of mechanotransduction markers, such as FAK, YAP, and TAZ (48 h). The results proved a significant increase in cell viability at 48 h (p < 0.05) and wound closure at 24 h (p < 0.001) of hGF grown on COL, with an increasing trend at all time-points. Furthermore, COL significantly induced the expression of FAK and YAP/TAZ (p < 0.05), thereby promoting the activation of mechanotransduction signaling pathways. Overall, these data suggest that COL, acting as a mechanical bio-scaffold, could represent a useful treatment for gingival rejuvenation and may possibly help in the resolution of oral pathologies.

Emerging Effects of Resveratrol Derivatives in Cells Involved in Oral Wound Healing: A Preliminary Study.

Recently, there has been an increasing interest in finding new approaches to manage oral wound healing. Although resveratrol (RSV) exhibited many biological properties, such as antioxidant and anti-inflammatory activities, its use as a drug is limited by unfavorable bioavailability. This study aimed to investigate a series of RSV derivatives (1a-j) with better pharmacokinetic profiles. At first, their cytocompatibility at different concentrations was tested on gingival fibroblasts (HGFs). Among them, derivatives 1d and 1h significantly increased cell viability compared to the reference compound RSV. Thus, 1d and 1h were investigated for cytotoxicity, proliferation, and gene expression in HGFs, endothelial cells (HUVECs), and oral osteoblasts (HOBs), which are the main cells involved in oral wound healing. For HUVECs and HGFs, the morphology was also evaluated, while for HOBs ALP and mineralization were observed. The results showed that both 1d and 1h did not exert negative effects on cell viability, and at a lower concentration (5 µM) both even significantly enhanced the proliferative rate, compared to RSV. The morphology observations pointed out that the density of HUVECs and HGFs was promoted by 1d and 1h (5 µM) and mineralization was promoted in HOBs. Moreover, 1d and 1h (5 µM) induced a higher eNOS mRNA level in HUVECs, higher COL1 mRNA in HGFs, and higher OCN in HOBs, compared to RSV. The appreciable physicochemical properties and good enzymatic and chemical stability of 1d and 1h, along with their promising biological properties, provide the scientific basis for further studies leading to the development of RSV-based agents useful in oral tissue repair.

CAR-T-Derived Extracellular Vesicles: A Promising Development of CAR-T Anti-Tumor Therapy.

Extracellular vesicles (EVs) are a heterogenous population of plasma membrane-surrounded particles that are released in the extracellular milieu by almost all types of living cells. EVs are key players in intercellular crosstalk, both locally and systemically, given that they deliver their cargoes (consisting of proteins, lipids, mRNAs, miRNAs, and DNA fragments) to target cells, crossing biological barriers. Those mechanisms further trigger a wide range of biological responses. Interestingly, EV phenotypes and cargoes and, therefore, their functions, stem from their specific parental cells. For these reasons, EVs have been proposed as promising candidates for EV-based, cell-free therapies. One of the new frontiers of cell-based immunotherapy for the fight against refractory neoplastic diseases is represented by genetically engineered chimeric antigen receptor T (CAR-T) lymphocytes, which in recent years have demonstrated their effectiveness by reaching commercialization and clinical application for some neoplastic diseases. CAR-T-derived EVs represent a recent promising development of CAR-T immunotherapy approaches. This crosscutting innovative strategy is designed to exploit the advantages of genetically engineered cell-based immunotherapy together with those of cell-free EVs, which in principle might be safer and more efficient in crossing biological and tumor-associated barriers. In this review, we underlined the potential of CAR-T-derived EVs as therapeutic agents in tumors.

Clinical and Radiological Evaluation of a Self-Condensing Bone Implant in One-Stage Sinus Augmentation: A 3-Year Follow-Up Retrospective Study.

Stabilization of dental implants in the sinus region with a bone height below 4 mm gen-erally requires a two-stage sinus floor elevation surgery. To improve this aspect, the aim of this retrospective study was to demonstrate the feasibility of performing a one-stage maxillary sinus augmentation using an innovative self-condensing implant design, even in case of a bone height close to 2 mm. Clinical and radiological outcomes from 54 patients (26 females; 28 males; 69 total implants positioned) were analyzed 3 years post-surgery. The three-dimensional grafts change was evaluated by Cone-Beam Computed Tomography (CBCT) before surgery (T0), immediately after surgery (T1), and 1-year post-surgery (T2). The sinus floor levels measured at the medial (M-W), middle (MD-W), and lateral (L-W) walls reported: M-W of 1.9 ± 2.4 mm (T1) and 1.7 ± 2.6 mm (T2); MD-W of -0.1 ± 2.7 mm (T1) and 0.7 ± 2.4 mm (T2); L-W of 3.1 ± 3.0 mm (T1) and 3.1 ± 3.0 mm (T2); besides a bone crest height (C-F) of 4.6 ± 2.0 mm (T1) and 12.1 ± 1.4 mm (T2). Moreover, after 3 years only 1 implant was lost, and so an implant survival rate of 98.55% was recorded. In conclusion, these results suggest the efficacy of using this implant design for a one-stage sinus lift approach, not only in terms of increased implant survival rate and decreased marginal bone loss, but also for its potential applicability in case of reduced bone height.

Effect of a 5-aminolevulinic acid gel and 660 nm red LED light on human oral osteoblasts: a preliminary in vitro study.

This study aimed to evaluate the effects of a new photodynamic protocol (ALAD-PDT) on primary human osteoblasts (hOBs). The ALAD-PDT protocol consists of a heat-sensitive gel with 5% 5-delta aminolevulinic acid commercialized as Aladent (ALAD), combined with 630 nm LED. For this purpose, the hOBs, explanted from human mandible bone fragments, were used and treated with different ALAD concentrations (10%, 50%, 100% v/v) incubated for 45 min and immediately afterwards irradiated with a 630 nm LED device for 7 min. The untreated and unirradiated cells were considered control (CTRL). The cellular accumulation of the photosensitizer protoporphyrin IX (PpIX), the proliferation, the alkaline phosphatase (ALP) activity, and the calcium deposition were assessed. All concentrations (10, 50, 100%) determined a significant increment of PpIX immediately after 45 min of incubation (0 h) with the highest peak by ALAD (100%). The consequent 7 min of light irradiation caused a slight decrease in PpIX. At 48 h and 72 h, any increment of PpIX was observed. The concentration 100% associated with LED significantly increased hOB proliferation at 48 h (+ 46.83%) and 72 h (+ 127.75%). The 50% and 100% concentrations in combination to the red light also stimulated the ALP activity, + 12.910% and + 14.014% respectively. The concentration 100% with and without LED was selected for the assessment of calcium deposition. After LED irradiation, a significant increase in calcium deposition was observed and quantified (+ 72.33%). In conclusion, the ALAD-PDT enhanced proliferation, the ALP activity, and mineralized deposition of human oral osteoblasts, highlighting a promising potential for bone tissue regeneration.

The Effects of 5% 5-Aminolevulinic Acid Gel and Red Light (ALAD-PDT) on Human Fibroblasts and Osteoblasts.

This study aimed to evaluate the effects of a new photodynamic protocol (ALAD-PDT), consisting of 5% 5-aminolevulinic acid-gel and 630 nm-LED, already used for antibacterial effects in the treatment of periodontitis, on human gingival fibroblasts (HGF) and primary human osteoblasts (HOB). HGF and HOB were incubated with different ALAD concentrations for 45 min, and subsequently irradiated with 630 nm-LED for 7 min. Firstly, the cytotoxicity at 24 h and proliferation at 48 and 72 h were assessed. Then the intracellular content of the protoporphyrin IX (PpIX) of the ROS and the superoxide dismutase (SOD) activity were investigated at different times. Each result was compared with untreated and unirradiated cells as the control. Viable and metabolic active cells were revealed at any concentrations of ALAD-PDT, but only 100-ALAD-PDT significantly enhanced the proliferation rate. The PpIX fluorescence significantly increased after the addition of 100-ALAD, and decreased after the irradiation. Higher ROS generation was detected at 10 min in HGF, and at 30 min in HOB. The activity of the SOD enzyme augmented at 30 min in both cell types. In conclusion, ALAD-PDT not only showed no cytotoxic effects, but had pro-proliferative effects on HGF and HOB, probably via ROS generation.

A Narrative Review on the Effectiveness of Bone Regeneration Procedures with OsteoBiol® Collagenated Porcine Grafts: The Translational Research Experience over 20 Years.

Over the years, several bone regeneration procedures have been proposed using natural (autografts, allografts, and xenografts) and synthetic (i.e., metals, ceramics, and polymers) bone grafts. In particular, numerous in vitro and human and animal in vivo studies have been focused on the discovery of innovative and suitable biomaterials for oral and maxillofacial applications in the treatment of severely atrophied jaws. On this basis, the main objective of the present narrative review was to investigate the efficacy of innovative collagenated porcine bone grafts (OsteoBiol®, Tecnoss®, Giaveno, Italy), designed to be as similar as possible to the autologous bone, in several bone regeneration procedures. The scientific publications were screened by means of electronic databases, such as PubMed, Scopus, and Embase, finally selecting only papers that dealt with bone substitutes and scaffolds for bone and soft tissue regeneration. A total of 201 papers have been detected, including in vitro, in vivo, and clinical studies. The effectiveness of over 20 years of translational research demonstrated that these specific porcine bone substitutes are safe and able to improve the biological response and the predictability of the regenerative protocols for the treatment of alveolar and maxillofacial defects.

Estrogen Receptor 1 (ESR1) and the Wnt/ß-Catenin Pathway Mediate the Effect of the Coumarin Derivative Umbelliferon on Bone Mineralization.

Bone physiology is regulated by osteoblast and osteoclast activities, both involved in the bone remodeling process, through deposition and resorption mechanisms, respectively. The imbalance between these two phenomena contributes to the onset of bone diseases. Among these, osteoporosis is the most common metabolic bone disorder. The therapies currently used for its treatment include antiresorptive and anabolic agents associated with side effects. Therefore, alternative therapeutic approaches, including natural molecules such as coumarin and their derivatives, have recently shown positive results. Thus, our proposal was to investigate the effect of the coumarin derivative umbelliferon (UF) using an interesting model of human osteoblasts (hOBs) isolated from osteoporotic patients. UF significantly improved the activity of osteoporotic-patient-derived hOBs via estrogen receptor 1 (ESR1) and the downstream activation of ß-catenin pathway. Additionally, hOBs were co-cultured in microgravity with human osteoclasts (hOCs) using a 3D system bioreactor, able to reproduce the bone remodeling unit in bone loss conditions in vitro. Notably, UF exerted its anabolic role by reducing the multinucleated cells. Overall, our study confirms the potential efficacy of UF in bone health, and identified, for the first time, a prospective alternative natural compound useful to prevent/treat bone loss diseases such as osteoporosis.

Vitamin E (Alpha-Tocopherol) Metabolism and Nutrition in Chronic Kidney Disease.

Vitamin E (alpha-tocopherol) is an essential micronutrient and fat-soluble antioxidant with proposed role in protecting tissues from uncontrolled lipid peroxidation. This vitamin has also important protein function and gene modulation effects. The metabolism of vitamin E depends on hepatic binding proteins that selectively retain food alpha-tocopherol for incorporation into nascent VLDL and tissue distribution together with esterified cholesterol and triglycerides. Chronic kidney disease (CKD) is a condition of oxidative stress and increased lipid peroxidation, that are associated with alterations of alpha-tocopherol metabolism and function. Specific changes have been reported for the levels of its enzymatic metabolites, including both short-chain and long-chain metabolites, the latter being endowed with regulatory functions on enzymatic and gene expression processes important for the metabolism of lipids and xenobiotics detoxification, as well as for the control of immune and inflammatory processes. Vitamin E therapy has been investigated in CKD using both oral vitamin E protocols and vitamin E-coated hemodialyzers, showing promising results in the secondary prevention of cardiovascular disease, as well as of immune and hematological complications. These therapeutic approaches are reviewed in the present article, together with a narrative excursus on the main findings indicating CKD as a condition of relative deficiency and impaired metabolism of vitamin E.