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Addressing the growing challenges of periodontal and peri-implant diseases, this study first reports a promising advancement in precision dentistry: an intricately formulated biopolymer spray designed for precise, localized drug delivery during tailored dental procedures. Poly (lactic-co-glycolic acid) (PLGA), recognized for its controlled release, biodegradability, and FDA-approved biocompatibility, forms the core of this formulation. Utilizing the double emulsion method, PLGA microparticles (PLGA-MPs) were loaded with dental antibiotics: sodium amoxicillin (AMX-Na), trihydrate amoxicillin (AMX-Tri), and metronidazole (Met). This antibiotic combination was thoughtfully selected to meet the distinctive requirements of the most impacting dental treatments. The newly developed biopolymer spray underwent thorough in-vitro analysis, revealing an optimized release curve for antibiotics over time, guaranteeing sustained therapeutic efficacy, and dose-dependent efficacy, accommodating personalized treatment approaches. The positive outcomes position the novel biopolymer spray formulation the leaders in advancing localized drug delivery during dental procedures. Moreover, the precise application and the tunable formulation meets the concept of precision medicine: in detail, this formulation represents a significant stride in dental therapeutics, significantly contributing to the predictability of dental implantology.

IntroductionOsteogenesis 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.MethodsIn 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.ResultsThe 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).DiscussionThe 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.

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

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

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.

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.

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.

Regenerative medicine typically aims to promote and improve the healing of tissues and organs of the human body, to restore the physiological architecture and the main functions lost.The combination of several scientific fields, including tissue engineering and cell biology, has led to the development of novel regenerative therapies that claim to obtain a better repairing, regenerating and replacing of tissues and organs damaged by chronic and acute diseases, or by severe traumatic injuries. In this landscape, the mesenchymal stem cells (MSCs) have been widely reported to self-regenerate and differentiate towards different tissues, under specific conditions and stimuli. Nowadays, MSCs are routinely used in autologous transplantation: the use of specific molecular effectors and biomimetic scaffolds populated with such MSCs has shown promising results both in vitro and in vivo experiments aimed to achieve a time-effective tissue reconstruction and a functional regeneration of complex organs.

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

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

Aim: Our research investigated the use of human serum (HS) as a safe and clinical-grade culture medium, using a new cell-model: hPCy-MSCs. This article is aimed to concretely applicate the concept of “waste-based regenerative dentistry” to translate it in future endo-periodontal applications. Methodology: HPCy-MSCs were cultured in 2 different mediums, both containing α-MEM: the 1st with 10% FBS (Control group), and the 2nd with 10% human serum (Test group).Cell proliferation and stemness assays, gene expression, immunophenotypic analysis and osteogenic differentiation were performed to verify our hypothesis. cDNA samples were amplified with qPCR.Experiments were performed in triplicate and analysed with statistical software. Results: The hPCy-MSCs cultivated in a medium with HS were morphologically similar to those cultivated with FBS, and showed a significantly higher proliferation rate. Von Kossa's staining revealed that osteoblasts from hPCy-MSCs in HS implemented with osteogenic induction factors, showed a better osteogenic activity, also confirmed by a significant upregulation of osteopotin (OPN) and matrix extracellular phosphoglycoprotein (MEPE). Conclusions: HPCy-MSCs cultivated in HS showed phenotypic stability and a clear regenerative binding, thus, suggesting these two components as a clinically-grade construct for future endo-periodontal therapies. Riassunto: Obiettivi: La nostra ricerca ha analizzato l’utilizzo del siero umano (HS) come mezzo di coltura sicuro e “clinical-grade”, per uso clinico, utilizzando un nuovo modello cellulare: le hPC-MSCs. Questo articolo ha lo scopo di applicare concretamente il concetto di “odontoiatria rigenerativa basata sui rifiuti biologici”, al fine di tradurlo in future applicazioni endo-periodontali. Materiali e metodi: Le HPCy-MSCs sono state coltivate in 2 mezzi di coltura diversi, entrambi contenenti α-MEM: il primo con 10% di FBS (gruppo di controllo) e il secondo con il 10% di siero umano (gruppo di test).Sono stati eseguiti saggi di proliferazione cellulare e di staminalità, espressione genica, analisi immunofenotipica e differenziamento osteogenico per verificare la nostra ipotesi di partenza. Campioni di cDNA sono stati amplificati con qPCR.Gli esperimenti sono stati eseguiti in triplicato e analizzati con software statistici. Risultati: Le hPC-MSC coltivate in un terreno con HS erano morfologicamente simili a quelle coltivate con FBS e mostravano un tasso di proliferazione significativamente più alto. La colorazione di Von Kossa ha rivelato che gli osteoblasti da hPC-MSC coltivate in HS implementato con fattori di induzione osteogenica hanno mostrato una migliore attività osteogenica, confermata anche da una significativa up-regolazione di osteopotina (OPN) e fosfoglicoproteina della matrice extracellulare (MEPE). Conclusioni: Le HPCy-MSC coltivate in HS hanno mostrato stabilità fenotipica e un chiaro atteggiamento rigenerativo, suggerendo quindi questo protocollo come un approccio clinicamente valido per le future terapie endo-periodontali. Keywords: Regenerative medicine, Stem cells, Osteogenesis, Human periapical cyst-MSCs, Translational research, Parole chiave: Medicina rigenerativa, Cellule staminali, Osteogenesi, Human periapical cyst-MSCs, Ricerca traslazionale

Stem cell-based therapies are the most promising breakthrough in almost all the fields of medicine. Despite stem cells are widely investigated, scientific community is still debating if stemness is a peculiar ability of a specific cytotype or if any differentiated cell may adopt stem-cell-like properties, according to an organ’s needs. Resident stem cells undergo to changes in chromatin structure depending from stimulus-responsive transcriptional programs highlighting how stem cells can be induced during both embryonic development and adult tissue regeneration in several different tissues, regardless of their biological niche. Biological wastes are usually considered as matter to be discharged, but in the last years, especially after the Nobel Prize in Physiology or Medicine to Randy Schekman, the interest toward the re-use of wasted tissues has become a hot topic in biomedical research.

The neuroendocrine system consists of various cells distributed in non-endocrine functional structures, able to synthesize amines and peptides with both local (paracrine) and systemic (endocrine) effects. The presence of such cells, belonging to the neuroendocrine system, is highlighted by the presence of neuroendocrine markers: the most suggestive are chromogranin A, synaptophysin, S-100B protein and glial fibrillary acidic protein. The presence of neuroendocrine markers is commonly associated to the occurrence of neuroendocrine cancers, currently representing the 0.5 percent of all malignant tumors. Nevertheless, neuroendocrine markers have been found to be overexpressed in rare oral neuroendocrine tumors, but also in quite common inflammatory conditions, such as severe periodontitis. The monitoring of neuroendocrine markers is, thus, a common factor of interest among dentistry and neurology: the analysis of neuroendocrine markers in oral diseases may be predictive and prognostic about the severity of neurological diseases, such as lateral amyotrophic sclerosis and traumatic brain injuries. The aim of this mini-review is to highlight the role of neuroendocrine molecules as advantageous diagnostic and prognostic markers for both oral diseases and neurodegenerative disorders.

Dental pulp is known to be an accessible and important source of multipotent mesenchymal progenitor cells termed dental pulp stem cells (DPSCs). DPSCs can differentiate into odontoblast-like cells and maintain pulp homeostasis by the formation of new dentin which protects the underlying pulp. DPSCs similar to other mesenchymal stem cells (MSCs) reside in a niche, a complex microenvironment consisting of an extracellular matrix, other local cell types and biochemical stimuli that influence the decision between stem cell (SC) self-renewal and differentiation. In addition to biochemical factors, mechanical factors are increasingly recognized as key regulators in DPSC behavior and function. Thus, microenvironments can significantly influence the role and differentiation of DPSCs through a combination of factors which are biochemical, biomechanical and biophysical in nature. Under in vitro conditions, it has been shown that DPSCs are sensitive to different types of force, such as uniaxial mechanical stretch, cyclic tensile strain, pulsating fluid flow, low-intensity pulsed ultrasound as well as being responsive to biomechanical cues presented in the form of micro- and nano-scale surface topographies. To understand how DPSCs sense and respond to the mechanics of their microenvironments, it is essential to determine how these cells convert mechanical and physical stimuli into function, including lineage specification. This review therefore covers some aspects of DPSC mechanoresponsivity with an emphasis on the factors that influence their behavior. An in-depth understanding of the physical environment that influence DPSC fate is necessary to improve the outcome of their therapeutic application for tissue regeneration.

Tissue regeneration in dentistry has demonstrated impressive progress over during the last decades compared to other medical sciences [...]

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.

Hyperbaric oxygen (HBO) therapy has been reported to be beneficial for treating many conditions of inflammation-associated bone loss. The aim of this work was to in vitro investigate the effect of HBO in the course of osteogenesis of human Mesenchymal Stem Cells (MSCs) grown in a simulated pro-inflammatory environment. Cells were cultured with osteogenic differentiation factors in the presence or not of the pro-inflammatory cytokine Tumor Necrosis Factor-α (TNF-α), and simultaneously exposed daily for 60 min, and up to 21 days, at 2,4 atmosphere absolute (ATA) and 100% O2. To elucidate osteogenic differentiation-dependent effects, cells were additionally pre-committed prior to treatments. Cell metabolic activity was evaluated by means of the MTT assay and DNA content quantification, whereas osteogenic and vasculogenic differentiation was assessed by quantification of extracellular calcium deposition and gene expression analysis. Metabolic activity and osteogenic properties of cells did not differ between HBO, high pressure (HB) alone, or high oxygen (HO) alone and control if cells were pre-differentiated to the osteogenic lineage. In contrast, when treatments started contextually to the osteogenic differentiation of the cells, a significant reduction in cell metabolic activity first, and in mineral deposition at later time points, were observed in the HBO-treated group. Interestingly, TNF-α supplementation determined a significant improvement in the osteogenic capacity of cells subjected to HBO, which was not observed in TNF-α-treated cells exposed to HB or HO alone. This study suggests that exposure of osteogenic-differentiating MSCs to HBO under in vitro simulated inflammatory conditions enhances differentiation towards the osteogenic phenotype, providing evidence of the potential application of HBO in all those processes requiring bone regeneration.

Optogenetics is a novel strategic field that combines light (opto-) and genetics (genetic) into applications able to control the activity of excitable cells and neuronal circuits. Using genetic manipulation, optogenetics may induce the coding of photosensitive ion channels on specific neurons: this non-invasive technology combines several approaches that allow users to achieve improved optical control and higher resolution. This technology can be applied to optical systems already present in the clinical-diagnostic field, and it has also excellent effects on biological investigations and on therapeutic strategies. Recently, several biomedical applications of optogenetics have been investigated, such as applications in ophthalmology, in bone repairing, in heart failure recovery, in post-stroke recovery, in tissue engineering, and regenerative medicine (TERM). Nevertheless, the most promising and developed applications of optogenetics are related to dynamic signal coding in cell physiology and neurological diseases. In this review, we will describe the state of the art and future insights on the impact of optogenetics on regenerative medicine.

Mesenchymal stem cells (MSCs) are attracting growing interest by the scientific community due to their huge regenerative potential. Thus, the plasticity of MSCs strongly suggests the utilization of these cells for regenerative medicine applications. The main issue about the clinical use of MSCs is related to the complex way to obtain them from healthy tissues; this topic has encouraged scientists to search for novel and more advantageous sources of these cells in easily accessible tissues. The oral cavity hosts several cell populations expressing mesenchymal stem cell like-features, furthermore, the access to oral and dental tissues is simple and isolation of cells is very efficient. Thus, oral-derived stem cells are highly attractive for clinical purposes. In this context, human periapical cyst mesenchymal stem cells (hPCy-MSCs) exhibit characteristics similar to other dental-derived MSCs, including their extensive proliferative potential, cell surface marker profile and the ability to differentiate into various cell types such as osteoblasts, adipocytes and neurons. Importantly, hPCy-MSCs are easily collected from the surgically removed periapical cysts; this reusing of biological waste guarantees a smart source of stem cells without any impact on the surrounding healthy tissues. In this review, we report the most interesting research topics related to hPCy-MSCs with a newsworthy discussion about the future insights. This newly discovered cell population exhibits interesting and valuable potentialities that could be of high impact in the future regenerative medicine applications.

Objective: There is a growing interest for the use of Y-TZP zirconia as core material in veneered all-ceramic prostheses. The objective of this study was to evaluate the influence of CET on the stress distribution of a porcelain layered to zirconia core single crowns by finite elements analysis. Material and methods: CET of eight different porcelains was considered during the analysis. Results: Results of this study indicated that the mismatch in CET between the veneering porcelain and the Y-TZP zirconia core has to be minimum (0.5–1 μm/mK) so as to decrease the growing of residual stresses which could bring chipping. Conclusions: The stress state due to temperature variation should be carefully taken into consideration while studying the effect of mechanical load on zirconia core crown by FEA. The interfacial stress state can be increased by temperature variation up to 20% with respect to the relative failure parameter (interface strength in this case). This means that stress due to mechanical load combined to temperature variation-induced stress can lead porcelain veneer–zirconia core interfaces to failure.

Bone regeneration involves several biological processes that consistently impact the quality of tissue healing. An important step consists of the local recruitment and differentiation of mesenchymal stem cells that migrate in the site to regenerate from bone marrow. Mesenchymal stem cells (MSCs) may be pushed towards osteogenic commitment by specific substances, often naturally present in plants. Yunnan Baiyao (YB) is a Chinese herbal medicine, mainly working through the synergic effect of terpenoid and steroidal saponins. YB is well known for its numerous biomedical effects, including the ability to favor improved bone tissue healing. In our in vitro study, we used adipose mesenchymal stem cells (ADSCs) as a study-model: We selected samples to harvest and isolate ADSCs and investigate their viability; moreover, we performed bone-related gene expression to evaluate the differentiation of MSCs. To confirm this behavior, we analyzed alkaline phosphate activity and calcium deposition, with ADSCs cultured in basal and osteogenic media, with YB at different concentrations in the medium, and at different time-points: 7, 14 and 21 days. Our results indicate that the synergic effect of terpenoid and steroidal saponins slightly favor the late ADSCs differentiation towards the osteoblasts phenotype. In osteogenic committed cells, the treatment with the lower dose of YB promoted the up-regulation of the alkaline phosphatase gene (ALPL) at day seven and 14 (p < 0.01); at day 21, the alkaline phosphatase (ALP) activity showed a slight increase, although in basal condition it maintains low rates. We assume that such molecular synergy can promote the osteogenic commitment of adipose mesenchymal stem cells, thus improving the timing and the quality of bone healing.

Allotropic 2D materials are the new frontier of materials science, due to their unique strategic properties and application within several sciences. Allotropic 2D materials have shown tunable physical, chemical, biochemical, and optical characteristics, and among the allotropic materials, graphene has been widely investigated for its interesting properties, which are highly required in biomedical applications. Recently, the synthesis of thin 2D boron sheets, developed on Ag(111) substrates, was able to create a 2D triangular structure called borophene (BO). Borophene has consistently shown anisotropic behavior similar to graphene. In this topical review, we will describe the main properties and latest applications of borophene. This review will critically describe the most interesting uses of borophene as part of electronic and optical circuits. Moreover, we will report how borophene can be an innovative component of sensors within biomedical devices, and we will discuss its use in nanotechnologies and theranostic applications. The conclusions will provide insight into the latest frontiers of translational medicine involving this novel and strategic 2D allotropic material.

Nowadays, the research of smart materials is focusing on the allotropics, which have specific characteristics that are useful in several areas, including biomedical applications. In recent years, graphene has revealed interesting antibacterial and physical peculiarities, but it has also shown limitations. Black phosphorus has structural and biochemical properties that make it ideal for biomedical applications: 2D sheets of black phosphorus are called Black Phosphorene (BP), and it could replace graphene in the coming years. BP, similar to other 2D materials, can be used for colorimetric and fluorescent detectors, as well as for biosensing devices. BP also shows high in vivo biodegradability, producing non-toxic agents in the body. This characteristic is promising for pharmacological applications, as well as for scaffold and prosthetic coatings. BP shows low cytotoxicity, thus avoiding the induction of local inflammation or toxicity. As such, BP is a good candidate for different applications in the biomedical sector. Properties such as biocompatibility, biodegradability, and biosafety are essential for use in medicine. In this review, we have exploited all such aspects, also comparing BP with other similar materials, such as the well-known graphene.

Peri-implantitis is an inflammatory disease affecting tissues surrounding dental implants. Although it represents a common complication of dental implant treatments, the underlying mechanisms have not yet been fully described. The aim of this study is to identify the role of titanium nanoparticles released form the implants on the chronic inflammation and bone lysis in the surrounding tissue. We analyzed the in vitro effect of titanium (Ti) particle exposure on mesenchymal stem cells (MSCs) and fibroblasts (FU), evaluating cell proliferation by MTT test and the generation of reactive oxygen species (ROS). Subsequently, in vivo analysis of peri-implant Ti particle distribution, histological, and molecular analyses were performed. Ti particles led to a time-dependent decrease in cell viability and increase in ROS production in both MSCs and FU. Tissue analyses revealed presence of oxidative stress, high extracellular and intracellular Ti levels and imbalanced bone turnover. High expression of ZFP467 and the presence of adipose-like tissue suggested dysregulation of the MSC population; alterations in vessel morphology were identified. The results suggest that Ti particles may induce the production of high ROS levels, recruiting abnormal quantity of neutrophils able to produce high level of metalloproteinase. This induces the degradation of collagen fibers. These events may influence MSC commitment, with an imbalance of bone regeneration.

Human oral-derived stem cells can be easily obtained from several oral tissues, such as dental pulp, periodontal ligament, from gingiva, or periapical cysts. Due to their differentiation potential, oral-derived mesenchymal stem cells are promising for tissue engineering and regenerative medicine. The regenerative ability showed by some oral tissues strongly depends on their sleeping adult stem cell populations that are able to repair small defects and to manage local inflammation. To date, researchers are working on effective and efficient methods to ensure safe and predictable protocols to translate stem cell research into human models. In the last decades, the challenge has been to finally use oral-derived stem cells together with biomaterials or scaffold-free techniques, to obtain strategic tools for regenerative and translational dentistry. This paper aims to give a clear point of view on state of the art developments, with some exciting insights into future strategies.

Recently, the main American associations in the dental field reported concerns regarding a film on the Netflix, Amazon, Apple, and Vimeo platforms that reported that endodontic treatments of root canals are linked to serious systemic pathologies, against any scientific evidence. This extreme case highlights how information, in a social networking era, is dramatically conditioned by a small number of users, leading to large scale consequences in political opinions, alimentary choices, or even in healthcare policy. It is urgent to demonstrate a strong awareness by the academic, institutional, and associative bodies in order to restore the correct flow of information on mass media and social networks.

Human periapical cyst mesenchymal stem cells (hPCy-MSCs) are a newly discovered cell population innovatively collected from inflammatory periapical cysts. The use of this biological waste guarantees a source of stem cells without any impact on the surrounding healthy tissues, presenting a valuable potential in tissue engineering and regenerative medicine applications. In the present study, hPCy-MSCs were collected, isolated, and seeded on three experimental mineral-doped porous scaffolds produced by the thermally-induced phase-separation (TIPS) technique. Mineral-doped scaffolds, composed of polylactic acid (PLA), dicalcium phosphate dihydrate (DCPD), and/or hydraulic calcium silicate (CaSi), were produced by TIPS (PLA-10CaSi, PLA-5CaSi-5DCPD, PLA-10CaSi-10DCPD). Micro-CT analysis evaluated scaffolds micromorphology. Collected hPCy-MSCs, characterized by cytofluorimetry, were seeded on the scaffolds and tested for cell proliferation, cells viability, and gene expression for osteogenic and odontogenic differentiation (DMP-1, OSC, RUNX-2, HPRT). Micro-CT revealed an interconnected highly porous structure for all the scaffolds, similar total porosity with 99% open pores. Pore wall thickness increased with the percentage of CaSi and DCPD. Cells seeded on mineral-doped scaffolds showed a superior proliferation compared to pure PLA scaffolds (control), particularly on PLA-10CaSi-10DCPD at day 12. A higher number of non-viable (red stained) cells was observable on PLA scaffolds at days 14 and 21. DMP-1 expression increased in hPCy-MSCs cultured on all mineral-doped scaffolds, in particular on PLA-5CaSi-5DCPD and PLA-10CaSi-10DCPD. In conclusion, the innovative combination of experimental scaffolds colonized with autologous stem cells from periapical cyst represent a promising strategy for regenerative healing of periapical and alveolar bone.

Tissue engineering is based on the interaction between stem cells, biomaterials and factors delivered in biological niches. Oral tissues have been found to be rich in stem cells from different sources: Stem cells from oral cavity are easily harvestable and have shown a great plasticity towards the main lineages, specifically towards bone tissues. Dental pulp stem cells (DPSCs) are the most investigated mesenchymal stem cells (MSCs) from dental tissues, however, the oral cavity hosts several other stem cell lineages that have also been reported to be a good alternative in bone tissue engineering. In particular, the newly discovered population of mesenchymal stem cells derived from human periapical inflamed cysts (hPCy-MSCs) have showed very promising properties, including high plasticity toward bone, vascular and neural phenotypes. In this topical review, the authors described the main oral-derived stem cell populations, their most interesting characteristics and their ability towards osteogenic lineage. This review has also investigated the main clinical procedures, reported in the recent literature, involving oral derived-MSCs and biomaterials to get better bone regeneration in dental procedures. The numerous populations of mesenchymal stem cells isolated from oral tissues (DPSCs, SHEDs, PDLSCs, DFSCs, SCAPs, hPCy-MSCs) retain proliferation ability and multipotency; these features are exploited for clinical purposes, including regeneration of injured tissues and local immunomodulation; we reported on the last studies on the proper use of such MSCs within a biological niche and the proper way to storage them for future clinical use.

The aim of this study was to evaluate the level of odontogenic differentiation of dental pulp stem cells (DPSCs) on hydrogel scaffolds derived from bone extracellular matrix (bECM) in comparison to those seeded on collagen I (Col-I), one of the main components of dental pulp ECM.DPSCs isolated from human third molars were characterized for surface marker expression and odontogenic potential prior to seeding into bECM or Col-I hydrogel scaffolds. The cells were then seeded onto bECM and Col-I hydrogel scaffolds and cultured under basal conditions or with odontogenic and growth factor (GF) supplements. DPSCs cultivated on tissue culture polystyrene (TCPS) with and without supplements were used as controls. Gene expression of dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP-1) and matrix extracellular phosphoglycoprotein (MEPE) was evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and mineral deposition was observed by Von Kossa staining.When DPSCs were cultured on bECM hydrogels, the mRNA expression levels of DSPP, DMP-1 and MEPE genes were significantly upregulated with respect to those cultured on Col-I scaffolds or TCPS in the absence of extra odontogenic inducers. In addition, more mineral deposition was observed on bECM hydrogel scaffolds as demonstrated by Von Kossa staining. Moreover, DSPP, DMP-1 and MEPE mRNA expressions of DPSCs cultured on bECM hydrogels were further upregulated by the addition of GFs or osteo/odontogenic medium compared to Col-I treated cells in the same culture conditions.These results demonstrate the potential of the bECM hydrogel scaffolds to stimulate odontogenic differentiation of DPSCs.

Dental pulp is an accessible source of multipotent mesenchymal stromal cells (MSCs). The perspective role of dental pulp stem cells (DPSCs) in regenerative medicine demands an in vitro expansion and in vivo delivery which must deal with the safety issues about animal serum, usually required in cell culture practice. Human platelet lysate (PL) contains autologous growth factors and has been considered as valuable alternative to fetal bovine serum (FBS) in cell cultures. The optimum concentration to be added of such supplement is highly dependent on its preparation whose variability limits comparability of results. By in vitro experiments, we aimed to evaluate a standardised formulation of pooled PL. A low selected concentration of PL (1%) was able to support the growth and maintain the viability of the DPSCs. The use of PL in cell cultures did not impair cell surface signature typically expressed by MSCs and even upregulated the transcription of Sox2. Interestingly, DPSCs cultured in presence of PL exhibited a higher healing rate after injury and are less susceptible to toxicity mediated by exogenous H2O2 than those cultured with FBS. Moreover, PL addition was shown as a suitable option for protocols promoting osteogenic and chondrogenic differentiation of DPSCs. Taken together, our results indicated that PL is a valid substitute of FBS to culture and differentiate DPSCs for clinical-grade use.

Introduction. Maxillary bone losses often require additional regenerative procedures: as a supplement to the procedures of tissue regeneration, a platelet concentrate called PRF (Platelet Rich Fibrin) was tested for the first time in France by Dr. Choukroun.Aim of the present study is to investigate, clinically and histologically, the potential use of PRF, associated with deproteinized bovine bone (Bio-Oss), as grafting materials in pre-implantology sinus grafting of severe maxillary atrophy, in comparison with a control group, in which only deproteinized bovine bone (Bio-Oss) was used as reconstructive material.Materials and Methods. 60 patients were recruited using the cluster-sampling method; inclusion criteria were maxillary atrophy with residual ridge < 5mm. The major atrophies in selected patients involved sinus-lift, with a second-look reopening for the implant insertion phase. The used grafting materials were: a) Bio-Oss and b) amorphous and membranous PRF together with Bio-Oss. We performed all operations by means of piezosurgery in order to reduce trauma and to optimize the design of the operculum on the cortical bone. The reopening of the surgical area was scheduled at 3 different times.Results. 72 sinus lifts were performed with subsequent implants insertions.We want to underline how the histological results proved that the samples collected after 106 days (Early protocol) with the adding of PRF were constituted by lamellar bone tissue with an interposed stroma that appeared relaxed and richly vascularized.Conclusions. The use of PRF and piezosurgery reduced the healing time, compared to the 150 days described in literature, favoring optimal bone regeneration. At 106 days, it is already possible to achieve good primary stability of endosseous implants, though lacking of functional loading.

Bone regeneration in craniomaxillofacial surgery represents an issue that involves both surgical and aesthetic aspects. The most recent studies on bone tissue engineering involving adipose-derived stromal/stem cells (ASCs) have clearly demonstrated that such cells can play a crucial role in the treatment of craniomaxillofacial defects, given their strong commitment towards the osteogenic phenotype. A deeper knowledge of the molecular mechanisms underlying ASCs is crucial for a correct understanding of the potentialities of ASCs-based therapies in the most complex maxillofacial applications. In this topical review, we analyzed the molecular mechanisms of ASCs related to their support toward angiogenesis and osteogenesis, during bone regeneration. Moreover, we analyzed both case reports and clinical trials reporting the most promising clinical applications of ASCs in the treatment of craniomaxillofacial defects. Our study aimed to report the main molecular and clinical features shown by ASCs, used as a therapeutic support in bone engineering, as compared to the use of conventional autologous and allogeneic bone grafts.

In the present work we analyzed the hormonal (salivary Cortisol; sC), immune (salivary Immunoglobulin A; sIgA) and cardiovascular (Heart rate, HR, and systolic blood pressure, SBP) responses induced by stress conditions in oral surgeons, randomly recruited according to their expertise level.Each surgeon performed three different surgical procedures with increasing degrees of technical difficulty and under time-limited conditions, to assess whether these variants may influence the risks of stress-induced secondary hypertension among the involved health professionals. sC and sIgA samples and cardiovascular function measurements were taken up before, during, and two hours after every surgery. Salivary samples and cardiovascular measurements were taken also during non-surgical days, as baseline controls.We observed that more experienced surgeons showed a higher stress management ability compared to those with less experience or, generally, younger, which are more exposed to the risks of developing secondary hypertension. Nevertheless, indipendently of sex and experience, oral surgeons are constantly exposed to high risks of developing stress-related diseases.On the basis of the issues addressed and the results obtained, we have highlighted the importance of the investigated stress biomarkers to monitor and to prevent stress-related pathologies among oral surgeons. This approach is aimed to emphasize the significance of these specific stress-biomarkers, which represent a powerful instrument to evaluate stress levels in oral surgeons, and that may help to reduce the most severe life-threatening risks to which they are daily exposed. In conclusion, final goal of this study is to suggest an useful guideline to monitor the stress levels of oral and maxillofacial surgeons in order to improve their quality of life, which is inevitably reflected on the quality of the performances provided and, finally, to prevent possible mistakes in their daily activities.

Introduction. The mechanical strength and the surface hardness of commercially available yttrium-doped zirconia were investigated. Furthermore, a comparative study of eight different ceramic veneers, to be used for the production of two-layered all-ceramic restorative systems, was carried out. Materials and Methods. Four types of zirconia specimens were analyzed, according to a standard ISO procedure (ISO 6872). Besides, two-layered zirconia-veneer specimens were prepared for three-point bending tests. Results. A strong effect of the surface roughness on the mechanical strength of zirconia specimens was observed. Finally, a comparative study of eight commercially available veneering ceramics shows different modes of failure between the selected veneers. Conclusion. The results indicate that close attention should be paid to the preparation of zirconia-based crowns and bridges by CAD/CAM process, because surface roughness has an important effect on the mechanical strength of the material. Finally, the results of the mechanical tests on two-layered specimens represent an important support to the choice of the veneering ceramic.

Due to the request of numerous patients to improve the aspect of the perioral area in combination with other types of cosmetic and reconstructive surgery, we started to use autologous fillers. In fact, there are numerous potential fillers that can be utilized during various operations executed in many bodily areas, such as the breast, abdomen, and face. The muscular fascia as well as the dense connective tissue which the surgeon encounters in various bodily areas during some stages of the operation, in fact, can be removed and replaced both by themselves or superimposed in order to increase their thickness. The insertion of the grafts is carried out by using a needle, but other methods can also be used with the same success. The consistency of the area treated, after a few days of edema, is very similar to the host area, and the volume obtained remains uniform in time (our followup is after 24 months). The time utilized for the removal and the insertion in the chosen area was only a few minutes. The result was extremely satisfactory in all the 30 patients treated, and there was no complication or side effects.

Background. Salivary glands tumours are uncommon, frequently benign lesions, prevalently located in the parotid gland (80%). Surgical decision making is based on the patient’s history, examination findings, imaging and fine needle aspiration (FNA). FNA is a pre-operative method with good ability in detecting malignancy. During surgery, therefore, Frozen section (FS) can differentiate benign lesions from malignant tumours, to reduce incorrect treatments, to increase the chances of conservative surgery and to better evaluate surgical margins. The aim of our study is to demonstrate the accuracy of the FS procedure in surgery of the salivary glands and to stress the need for dedicated pathology units specialized in lesions of the oral cavity. Methods . The study included 499 patients who underwent surgery from May 2005 and October 2014. An intra-operative frozen section procedure was done for 288 of them. All frozen sections were compared with the final results. The cases were classified by site, nature of the lesion and histotype, according to the WHO classification. Comparison was made between the intra-operative and the definitive diagnosis. Results. Of the 288 FS procedures, 259 were for neoplastic lesions, 199 of which benign and 60 malignant, and 29 for non-neoplastic lesions. Of the 259 neoplastic FS results, 2 were shown to be false positives and 2 were diagnosed as different malignant types. Of the 29 non-neoplastic FS results, 4 were false negatives. Conclusions. Our results showed that the accuracy of frozen section procedure is 98% for salivary glands tumors. The highest concordance between frozen section and the definitive diagnosis was for inflammatory processes (99%), pleomorphic adenoma (98%), Warthin’s tumor (97%) and malignant neoplasms (96%). In conclusion, based on these findings, frozen section of the salivary glands may be proposed as a routine procedure and should be used in decision-making.