Functionalized magnesium alloys obtained by superplastic forming process retain osteoinductive and antibacterial properties: An in-vitro study.

OBJECTIVES: This study aimed to investigate the biocompatibility, osteogenic and antibacterial activity of biomedical devices based on Magnesium (Mg) Alloys manufactured by Superplastic Forming process (SPF) and subjected to Hydrothermal (HT) and Sol-Gel Treatment (Sol-Gel). METHODS: Mg-SPF devices subjected to Hydrothermal (Mg-SPF+HT) and Sol-Gel Treatment (Mg-SPF+Sol-Gel) were investigated. The biocompatibility of Mg-SPF+Sol-Gel and Mg-SPF+HT devices was observed by indirect and direct cytotoxicity assays, whereas the colonization of sample surfaces was assessed by confocal microscopy. qRT-PCR analysis and microbial growth curve analyses were employed to evaluate the osteogenic and antibacterial activity of both SPF-Mg treated devices, respectively. RESULTS: Mg-SPF+HT and Mg-SPF+Sol-Gel showed a high degree of biocompatibility. Analysis of mRNA expression of osteogenic genes in cells cultured on Mg-treated devices revealed a significant upregulation of the expression levels of BMP2 and Runx-2. Furthermore, the bacterial growth in strains developed in contact with both the Mg-SPF+HT and Mg-SPF+Sol-Gel devices was lower than that observed in the control. SIGNIFICANCE: Hydrothermal and Sol-Gel Treatments of Mg alloys obtained through the SPF process demonstrated bioactive, osteogenic and antibacterial activity, offering a promising alternative to conventional Mg-based devices. The obtained Mg-based materials may have the potential to enhance the tunability of temporary devices in maxillary reconstruction, eliminating the need for second surgeries, and ensuring a good bone reconstruction and a reduced implant failure rate due to bacterial infections.

Clinical Impact of "Real World Data" and Blockchain on Public Health: A Scoping Review.

The digitisation of healthcare has allowed a significant rethinking of the previous clinical protocols, improving their interoperability through substantial standardisation. These technological advances have ensured that data are comparable, as they are obtained from 'reliable' and certified processes; however, there are billions of data that are neither structured nor quality-controlled. They are collectively referred to as 'Real World Data' (RWD). Blockchain (BC) is a procedure with specific characteristics and algorithms that ensure that the stored data cannot be tampered with. Nowadays, there is an increasing need to rethink blockchain in a one-health vision, making it more than just a 'repository' of data and information, but rather an active player in the process of data sharing. In this landscape, several scholars have analysed the potential benefits of BC in healthcare, focusing on the sharing and safety of clinical data and its contact tracing applications. There is limited research on this matter; moreover, there is a strategic interest in managing RWD in a reliable and comparable way, despite the lack of knowledge on this topic. Our work aims to analyse systematically the most impacting literature, highlighting the main aspects of BC within the context of the new digital healthcare, and speculating on the unexpressed potential of RWD.

Entropy Meets Physiology: Should We Translate Aging as Disorder?

Aging is characterized by an alteration of several physiological processes and biological pathways that leads to an increased susceptibility to age-related diseases and death. Normally, multipotential stem/progenitor cells may contribute to tissue homeostasis, and to minimize the age-depending DNA damage. Scientific research has demonstrated that aging induces several complex changes affecting even the mesenchymal stromal/stem cells (MSCs) ability to self-renew, differentiate, and immunomodulate the human tissues, causing further alterations in the local microenvironment. Cellular senescence can thus be considered as an overall response to several damages. Accordingly, aging seems to create the proper conditions to decrease the tissue's metabolic performance, and the cell-to-cell communication, resulting in a progressive tissue destruction; on the other hand, the MSCs functions appear to be severely reduced. This concise review summarizes the main alterations affecting the MSCs during aging, and it also explains the role of inflammation as a key player in age-related syndromes. The hypothesis is to suggest a parallelism between the thermodynamic concept of "entropy" and biological aging, speculating that both can increase within irreversible systems and both lead toward an irreversible disorder; so, the question is: should we translate aging as disorder?

Influence of crestal and sub-crestal implant position on development of peri-implant diseases: a 5-year retrospective analysis.

OBJECTIVES: The aim of the present study was to evaluate the influence of crestal and subcrestal implant position on development of peri-implant diseases. MATERIALS AND METHODS: The study was designed as a retrospective clinical and radiographic analysis. Implant-supported fixed dental prostheses were allocated in two groups: with the shoulder (i) placed in sub-crestal level and (ii) placed at bone level. For each patient, the following clinical variables were assessed: FMPS, FMBS, PlI, BOP, and PD. After prothesis delivery, an intraoral radiograph was obtained; this exam was performed also at 5 years of observation period. RESULTS: No statistically significant difference was found in terms of FMPS and FMBS at baseline and after 5 years follow-up (P < 0.05). A statistically significant difference was assessed between PD of control group and test group (P = 0.042). Patient-based analysis showed a 25.6% of peri-implant mucositis and 32.6% of peri-implantitis for implants placed with the shoulder in crestal position, while for implants inserted in sub-crestal position the percentage of peri-implant-mucositis and peri-implantitis were 19%; no statistically significant difference was found between groups after 5 years (P < 0.05). CONCLUSIONS: Within the limitation of the present study, the clinical and radiographic outcomes showed that the percentage of peri-implant mucositis and peri-implantitis was not statistically significant for both groups after 5 years follow-up. CLINICAL RELEVANCE: The outcomes of present study clinically demonstrated that a deep position of implant shoulder did not provide any benefits. On the contrary, it may be considered a possible risk indicator for implant diseases.

Expanding the genetic and clinical spectrum of osteogenesis imperfecta: identification of novel rare pathogenic variants in type I collagen-encoding genes.

Introduction: Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous skeletal disorder. The majority of affected cases are attributed to autosomal dominant pathogenic variants (PVs) found in the COL1A1 and COL1A2 genes, which encode type I collagen. However, PVs in other genes involved in collagen posttranslational modification, processing, crosslinking, osteoblast differentiation, and bone mineralization have also been associated with OI. Methods: In this study, we present the results of next-generation sequencing (NGS) analysis using a custom panel of 11 genes known to be associated with OI. This clinical study enrolled a total of 10 patients, comprising 7 male and 3 female patients from 7 families, all from the Puglia Region in South Italy, providing a detailed overview of their age, gender, family history, OI type, and non-skeletal features. Results: The genetic analysis revealed 5 PVs in the COL1A1 gene and 2 PVs in the COL1A2 gene. Importantly, three of these PVs have not been previously reported in the literature. These include two novel heterozygous frameshift PVs in COL1A1 (c.2890_2893del and c.3887del) and one novel heterozygous missense PV in COL1A2 (c.596G>T). Discussion: The identification of these previously unreported PVs expands the variant spectrum of the COL1A1 and COL1A2 genes and may have implications for accurate diagnosis, genetic counselling, and potential therapeutic interventions in affected individuals and their families.

Advances in Dental Implants, Tissue Engineering and Prosthetic Materials.

Scientific research has achieved numerous milestones in the field of materials applied to medicine for biomedical prosthetics [...].

Unlocking the Potential of Dental-Derived Mesenchymal Stem Cells in Regenerative Medicine.

Over the past few decades, life expectancy has been increasing in several countries [...].

Critical Overview on Regenerative Medicine: New Insights into the Role of Stem Cells and Innovative Biomaterials.

Regenerative medicine represents a novel and intriguing field of medicine [...].

PReferentially Expressed Antigen in MElanoma (PRAME): preliminary communication on a translational tool able to early detect Oral Malignant Melanoma (OMM).

Oral malignant melanoma (OMM) has a prevalence less than 1% of all melanomas and it commonly develops on the oral mucosa following a slow and unspecific transformation of unstable melanocytic lesions, often resulting in a diagnostic delay. The marker PReferentially Expressed Antigen in MElanoma (PRAME) seems to be a valid tool to investigate the biological and histological nature of cutaneous melanocytic lesions, but to date its use to characterize pigmented lesions in the oral cavity is largely unexplored. The aim of this study was to create preliminary knowledge on the PRAME expression in OMM, and to compare its expression respect to other dysplastic pigmented lesions of the oral cavity. Interestingly, PRAME has been demonstrated to be reliable in the clinical conditions investigated in our pilot study; in fact, it has clearly differentiated the cases of Melanoma, which showed diffuse and intense positivity (score 6+/7+) to PRAME, from the other melanocytic nevi, which resulted to be mainly negative to PRAME. This means a better differential diagnosis, a reliable early diagnosis and a proper clinical/surgical management of the oncological lesions. In conclusion, PRAME can be a valid qualitative marker for differential diagnosis, not only in cutaneous melanomas, but also in malignant melanoma of the entire head and neck area.

Comparative in vitro study on biomechanical behavior of zirconia and polyetheretherketone biomaterials exposed to experimental loading conditions in a prototypal simulator.

Zirconia and polyetheretherketone (PEEK) are two biomaterials widely investigated as substitute for metals in oral prosthetic rehabilitation. To achieve a proper biomechanical behavior, the prosthetic biomaterials must ensure a good resistance to loads, as this is a crucial characteristic enabling their use in dental applications. The aim of this study was to investigate differences in the fracture resistance of different biomaterials in an experimental environment: fixed partial dentures (FPDs) screwed in a prototype of biomimetic mandible. 10 Samples of FPDs were allocated in 2 groups (A and B): Group A (n=5) involved FPDs in zirconia-ceramic, and Group B (n=5) involved FPDs in PEEK-composite. The samples were loaded by means of a three-point bending mechanical test, and the load to fracture has been evaluated generating a point-by-point graphics (speed/load and time/deformation). The samples were further analyzed by micro-computed tomography (micro-CT) and described under experimental loading conditions. Zirconia-ceramic FDPs were the samples reporting the worst results, showing a lower value of vertical displacement with respect to PEEK-based samples. The micro-CT results have further confirmed the preliminary results previously described. This in vitro study aims to give analytic data on the reliability of PEEK as a reliable and strong biomaterial for prosthetic treatments.

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.

Epigallocatechin-3-gallate improves the biocompatibility of bone substitutes in dental pulp stem cells.

BACKGROUND: The Biocompatibility between osteoprogenitor cells and bone substitutes is necessary for cell differentiation and osteogenesis. The aim of this study was to assess the in vitro effect of bovine (Geistlich BioOss®), porcine (OsteoBiol Gen-Os®) and beta-tricalcium phosphate (Cerasorb M®) bone substitutes, and their combination with polyphenol epigallocatechin-3-gallate (EGCG), upon cultured dental pulp stem cells (DPSCs). METHODS: The DPSCs were isolated from third molars extracted from healthy individuals and seeded with 5 mg/ml of Bio-Oss® (BO), Gen-Os® (GO) and Cerasorb® (CE) in combination with EGCG 1 µM. The effects were evaluated based on cell viability / cytotoxicity assay (MTT, cell viability staining test), cell migration, scanning electron microscopy (SEM), and alkaline phosphatase (ALP) activity. RESULTS: BO and CE produced negative effects upon cell viability and migration, and GO and CE resulted in deficient cell adhesion. On the other hand, all the biomaterials exerted no negative effects upon ALP activity. Interestingly, the addition of EGCG reverted the cytotoxic effect and the loss of migration capacity in the BO and CE groups, and improved cell adhesion in the GO and CE groups. Furthermore, EGCG promoted an overall increased in ALP activity. CONCLUSION: The addition of EGCG to the tested biomaterials BO, GO and CE reverts their negative impact on DPSCs, and improves their biocompatibility with cultured DPSCs. The use of EGCG, thus, appears to be a promising strategy for restoring and enhancing the osteoconductive properties of BO, GO and CE in bone regeneration treatments.

Turner Syndrome Mosaicism 45,X/46,XY with Genital Ambiguity and Duchenne Muscular Dystrophy: Translational Approach of a Rare Italian Case.

Turner syndrome (gonadal dysgenesis with short stature and sterility) is characterized by chromosomal karyotype 45,X in 50% of cases or by mosaicism (45,X/46,XX and 45,X/46,XY) in 30-40% or X structural defects (deletions, long arm isochromosome, ring chromosome). When mosaic Turner syndrome (TS) occurs with a Y chromosome, there may be ambiguous genitalia. Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disease with an X-Linked recessive pattern of inheritance that predominantly affects males, while females are usually asymptomatic. DMD has also been observed in groups of females affected by TS, not homozygous for the mutation. Here, we report a case of an Indian neonate born with ambiguous genitalia diagnosed prenatally by ultrasound who had a karyotype of 45,X/46,XY and who also had Duchenne muscular dystrophy caused by a de novo mutation in the DMD gene. Physical examination was normal without the typical dysmorphic features of TS with the exception of the genitourinary system showing ambiguous genitalia. Gender was assigned as female. At the age of three years, she had increasing difficulty walking, running, jumping and climbing stairs, proximal upper and lower extremity muscle weakness and a positive Gowers' sign. In addition, the serum creatine kinase (CK) value was over 30X the upper limit of normal. This study shows that DMD can occur in females with TS having 45,X/46,XY mosaicism and that this coexistence should be considered in women affected by TS who start to develop potential typical symptoms such as motor or developmental delay.

Impact of Oral Mesenchymal Stem Cells Applications as a Promising Therapeutic Target in the Therapy of Periodontal Disease.

Periodontal disease is a chronic inflammatory condition affecting about 20-50% of people, worldwide, and manifesting clinically through the detection of gingival inflammation, clinical attachment loss, radiographically assessed resorption of alveolar bone, gingival bleeding upon probing, teeth mobility and their potential loss at advanced stages. It is characterized by a multifactorial etiology, including an imbalance of the oral microbiota, mechanical stress and systemic diseases such as diabetes mellitus. The current standard treatments for periodontitis include eliminating the microbial pathogens and applying biomaterials to treat the bone defects. However, periodontal tissue regeneration via a process consistent with the natural tissue formation process has not yet been achieved. Developmental biology studies state that periodontal tissue is composed of neural crest-derived ectomesenchyme. The aim of this review is to discuss the clinical utility of stem cells in periodontal regeneration by reviewing the relevant literature that assesses the periodontal-regenerative potential of stem cells.

Regenerative Medicine: Role of Stem Cells and Innovative Biomaterials 2.0.

Regenerative medicine has constantly increased its field of influence over the last few years [...].

Stem Cells from Dental Sources: Translational Applications in Medicine and Novel Approaches.

Recently, regenerative medicine has been attracting interest from scientific groups working on translational applications of applied medical sciences [...].

Potential impact of functional biomolecules-enriched foods on human health: A randomized controlled clinical trial.

Naturally occurring milk compounds have recently been investigated for their health-promoting properties; in fact, their anti-microbial, immuno-modulatory, antioxidant and anti-thrombotic activities, have increasingly gained interest within the scientific community. We have reported a translational, randomized, controlled clinical trial (RCT) on human subjects with a moderate to high cardiovascular risk, and a body mass index (BMI) >25.1 kg/m2, to evaluate the clinical impact of biomolecules-enriched Mediterranean Buffalo (Bubalus bubalis) milk and its derived dairy foods, produced with innovative breeding techniques. The experimental arm involved patients that followed a diet including the above-described products (treated group; n= 11); the control arm was based on a diet including cow milk and its dairy products (control group; n= 9). The results of this study have been statistically evaluated, pointing out a specific significance related to the comparative analysis of the blood pressure among the 2 arms; in fact, this value showed a significant improvement in an extremely short experimental time. Nevertheless, this study also reported not-significant results that were indicative of an interesting and promising tendency in modulating specific diet-depending haematological and biomedical values. In conclusion, this RCT has assessed that the foods derived from buffalo milk naturally enriched with biomolecules, was able to improve the overall blood glucose levels, the BMI and the body weight. These preliminary results are suitable for the design of future strategies in the prevention of cardiometabolic diseases, thus improving the overall quality of life and the policies of healthcare management.

Toll-Like Receptors in Stem/Progenitor Cells.

One of the bridges that control the cross-talk between the innate and adaptive immune systems is toll-like receptors (TLRs). TLRs interact with molecules shared and maintained by the source pathogens, but also with endogenous molecules derived from injured tissues (damage/danger-associated molecular patterns - DAMPs). This is likely why some kinds of stem/progenitor cells (SCs) have been found to express TLRs. The role of TLRs in regulating basal motility, proliferation, processes of differentiation, self-renewal, and immunomodulation has been demonstrated in these cells. In this book chapter, we will discuss the many different functions assumed by the TLRs in SCs, pointing out that, depending on the context and the type of ligands they perceive, they may have different effects. In addition, the role of TLR in SC's response to specific tissue damage and in reparative processes will be addressed, as well as how the discovery of molecules mediating TLR signaling's differential function may be decisive for the development of new therapeutic strategies. Given the available studies on TLRs in SCs, the significance of TLRs in sensing an injury to stem/progenitor cells and evaluating their action and reparative activity, which depends on the circumstances, will be discussed here. It could also be possible that SCs used in therapy could theoretically be exposed to TLR ligands, which could modulate their in vivo therapeutic potential. In this context, we need to better understand the mechanisms of action of TLRs on SCs and learn how to regulate these receptors and their downstream pathways in a precise way in order to modulate SC proliferation, survival, migration, and differentiation in the pathological environment. In this way, cell therapy may be strengthened and made safer in the future.