Critical Overview on Pure Chitosan-based Scaffolds for Bone Tissue Engineering: Clinical insights in Dentistry.

Bone Tissue Engineering (BTE) is a field of regenerative medicine continuously improving, thanks to the development of new biomaterials used as grafts or scaffolds for repairing bone defects. In recent years, chitosan, a natural biopolymer extracted mainly from crustacean shells, has demonstrated unique and desirable characteristics for BTE applications, such as: biocompatibility, biodegradability, and osteoconductive behavior. Additionally, the presence of numerous active amine groups in its chemical structure allows it to be easily modified. Data suggest that chitosan scaffolds are highly biomimetic, and show an interesting bioactivity, and antibacterial behavior. We have demonstrated, in a critical overview, how chitosan-based scaffolds may hold great interest for BTE applications in medical and dental applications. Future research should be focused on the use of chitosan-scaffolds combined with other biomaterials or bioactive molecules, to increase their overall regenerative potential, also in critical-sized defects. In conclusion, chitosan can be considered a promising biomaterial in BTE and clinical dentistry.

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.

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.

A Dedifferentiation Strategy to Enhance the Osteogenic Potential of Dental Derived Stem Cells.

Dental stem cells (DSCs) holds the ability to differentiate into numerous cell types. This property makes these cells particularly appropriate for therapeutic use in regenerative medicine. We report evidence that when DSCs undergo osteogenic differentiation, the osteoblast-like cells can be reverted back to a stem-like state and then further differentiated toward the osteogenic phenotype again, without gene manipulation. We have investigated two different MSCs types, both from dental tissues: dental follicle progenitor stem cells (DFPCs) and dental pulp stem cells (DPSCs). After osteogenic differentiation, both DFPCs and DPSCs can be reverted to a naïve stem cell-like status; importantly, dedifferentiated DSCs showed a greater potential to further differentiate toward the osteogenic phenotype. Our report aims to demonstrate for the first time that it is possible, under physiological conditions, to control the dedifferentiation of DSCs and that the rerouting of cell fate could potentially be used to enhance their osteogenic therapeutic potential. Significantly, this study first validates the use of dedifferentiated DSCs as an alternative source for bone tissue engineering.

Organoids in Translational Oncology.

Translational medicine aims to translate the most promising preclinical research into clinical practice. Oncology is a continuously growing medical field: the scientific research on cancer biology is currently based on in vitro experiments, carried out on tissue culture plates (TCPs) and other 2D samples. In this context, 3D printing has greatly improved the biofabrication of new biological matrices that mimic the extracellular environments, which may characterize healthy from cancerous tissues. Organoids have recently been described in several reports on scientific literature. The term that better describes such organoids-based tumoral tissues is "tumoroids". Tumoroids are substantially "tumor-like organoids", typically deriving from primary tumors harvested from patients. This topical review aims to give an update on organoids applied in translational medicine, paying specific attention to their use in the investigation of the main molecular mechanisms of cancer onset and growth, and on the most impacting strategies for effective targeted therapies.

Promising Scaffold-Free Approaches in Translational Dentistry.

Regenerative medicine has recently improved the principal therapies in several medical fields. In the past ten years, the continuous search for novel approaches to treat the most common dental pathologies has developed a new branch called regenerative dentistry. The main research fields of translational dentistry involve biomimetic materials, orally derived stem cells, and tissue engineering to populate scaffolds with autologous stem cells and bioactive growth factors. The scientific literature has reported two main research trends in regenerative dentistry: scaffold-based and scaffold-free approaches. This article aims to critically review the main biological properties of scaffold-free regenerative procedures in dentistry. The most impactful pros and cons of the exosomes, the leading role of hypoxia-based mesenchymal stem cells (MSCs), and the strategic use of heat shock proteins in regenerative dentistry will be highlighted and discussed in terms of the use of such tools in dental regeneration and repair.

Management of Endodontic and Periodontal Lesions: the Role of Regenerative Dentistry and Biomaterials.

Regenerative dentistry represents a novel interdisciplinary approach involving biomaterials, several molecules and mesenchymal stem cells (MSCs), preferably derived from oral tissues. The pivotal role of MSCs depends on the fact that they can differentiate into different cell lineages and have the strategic role to release bioactive substances that stimulate the renewal and regeneration of damaged tissues. The role of regenerative dentistry is promising in all the branches of dentistry: the most intriguing application is related to the management of endodontic and periodontal defects, overcoming the surgical approach and the implantology as a consequence of a poorly efficient therapeutic plan.

Exosomes from Human Periapical Cyst-MSCs: Theranostic Application in Parkinson's Disease.

The scientific community continuously strives to get new disease models, to discover early markers or novel therapeutic approaches, improving the diagnosis and prognosis of several human pathologies. Parkinson's Disease (PD) is characterized by a long asymptomatic phase, characterized by a selective loss of dopaminergic neurons. Recently, the human Periapical Cyst-Mesenchymal Stem Cells (hPCy-MSCs) have been differentiated in functional dopaminergic neurons: such oral-derived MSCs and the hPCy-MSCs-derived exosomes may represent a strategic and useful in vitro study-model, as well as intriguing therapeutic carriers. Circadian rhythm (CR) alteration variously impacts on PD pathways: an interesting research target is represented by the analysis of the exosomes released by dopaminergic neurons, derived from neural-differentiated hPCy-MSCs, after having reproduced in-vitro PD-like conditions. This review aims to describe the crosstalk among some aspects of circadian rhythm related to the onset of PD and the exosomes released by cells of PD patients. More in detail: the first part of this article will describe the main characteristics of circadian rhythm and the involvement of the exosomes found to be effective in the pathogenesis of PD. Finally, the authors will suggest how those exosomes derived from dopaminergic neurons, obtained by oral-derived stem cells (hPCy-MSCs) may represent a smart model for the in vitro research on PD, to find new biomarkers, to test new drugs or, fatally, to find new pathways applicable in future therapeutic approaches.