University of Dental Medicine

Cell fate determination is controlled by a complex network of cell signalling pathways. The process of osteoblasts transforming into osteocytes can be described as several distinct stages: from osteoblasts to early osteocytes, then to mature osteocytes, deeply embedded in the bone matrix within spaces called lacunae and canaliculi. During this transition, the committed osteoblast undergoes significant changes, including loss of proliferative capacity, the extension of multiple slender processes, and the secretion of minerals onto the collagenous scaffold. These osteocytes are arranged in an ordered manner with respect to neighbouring cells, suggesting that osteoblast-to-osteocyte transition is a tightly regulated developmental event. In this review, we summarise recent findings on Notch expression during osteoblast-to-osteocyte transition and propose a regulatory role for Notch in coordinating adjacent osteoblast activity during this process. We further discuss the implications of Notch signalling in the alveolar bone, as emerging data indicate that Notch participates in the osteogenic commitment of periodontal and alveolar progenitor cells, modulates force-driven remodelling, contributes to inflammatory osteolysis in periodontitis, and presents opportunities for biomaterial-guided alveolar bone regeneration and improved osseointegration around dental implants. This review highlights Notch as a potential master regulator of alveolar bone biology, suggesting that precise spatial and temporal control of Notch signalling may offer new therapeutic avenues to maintain alveolar bone homeostasis.

Alazami syndrome is a neurodevelopmental disorder characterized by postnatal growth retardation, moderate to severe intellectual disability, and facial dysmorphology. It is caused by biallelic variants in the transcriptional regulator La ribonucleoprotein 7 (LARP7), where frameshift variants accounted for the majority of cases. The current study presents 7 new patients, including 3 males and 4 females from 3 unrelated families. Careful and thorough clinical examination identified novel oro-dental disease abnormalities, including a prominent premaxilla and enamel defects. The detected variants (c.1113_1116del, c.997 + 2T > C and c.518T > C) were not reported in the previous studies. The substitution c.518T > C represented the second missense variant to be identified in patients with Alazami syndrome. Male patients from the three families fulfilled ≥ 2 clinical warning signs of primary immunodeficiency. Lymphocyte subset counts and immunoglobulin levels were estimated in patients from two families. The values were within reference ranges, with only minor non-significant alterations in cytotoxic T-cell counts. A functional assay of B lymphocyte response was performed in one family, demonstrating impaired Streptococcus pneumoniae IgG antibody production following Pneumovax vaccination in the male patient, while his female sibling mounted an adequate response. In conclusion, the disease has a wide range of symptoms, which vary greatly among the affected patients. Our study expanded the clinical and molecular spectrum of the disorder and highlighted immunodeficiency as an underrecognized disease feature, potentially with a male sex predilection.

To design and assess a 3D-printed pediatric dentistry simulator and to evaluate its perceived educational value and realism through student and expert feedback. A maxillary simulator that is mountable on phantom heads was developed and produced by desktop stereolithography with single-use inserts, enabling proximal caries management/restoration, pulpotomy, pulpectomy, immature-incisor apexification, pit-and-fissure sealant application, tooth replantation with splinting, and space-maintainer placement. Both students and experts tested the device and completed a purpose-built 22-item Likert questionnaire assessing perceived clinical realism, perceived educational value, and overall appraisal. Group responses were compared using Wilcoxon rank-sum tests (p<0.05). Thirty-five participants (17 students, 18 experts) evaluated the device. Students generally rated clinical realism higher than experts did. Both groups awarded high scores for perceived educational value. The conclusive items "reliable teaching tool" and "asset to preclinical training" received mean scores of 4.82 and 4.94 among students and 4.44 and 4.25 among experts, respectively. Suggested improvements included gingival texture, space-maintainer design, endodontic haptics, canine morphology, and radiographic compatibility. This 3D-printed pediatric dentistry simulator was received positively by students and experts and was perceived as an acceptable and educationally relevant tool for preclinical pediatric dentistry training, while also highlighting specific areas for technical refinement.

BackgroundThe architecture of bone substitute scaffolds—particularly pore size and organization—plays a crucial role in orchestrating immune responses, osteogenesis and angiogenesis. Yet, the mechanisms linking scaffold design to the temporal dynamics of bone regeneration remain partially understood. To address this, we established a refined in vivo model that integrates histological, molecular, and immunological analyses from a single explant, enabling spatially resolved insight into the bone healing process and dynamics.MethodsUsing a dynamic rabbit calvarial model, we investigated 3D-printed calcium phosphate cement scaffolds designed with concomitant macroarchitectures of 250 μm and 500 µm pores within a single construct, allowing direct intra-animal comparison. The model recapitulated three vertically migrating zones of regeneration—regenerative, osteogenic, and granulation—captured at 2 and 4 weeks. Histomorphometric analyses quantified bone ingrowth, while laser microdissection enabled zone-specific transcriptomic profiling from paraffin-embedded sections previously used for (immuno-)histology. Gene expression was further validated by qPCR and complemented with immunohistochemical characterization of macrophage and neutrophil populations.ResultsHistological analysis revealed a consistent spatial organization of bone regeneration across conditions. After 4 weeks, scaffolds with 250 µm pores exhibited more homogeneous and advanced bone formation than those with 500 µm pores or particulate substitutes. Transcriptomic analysis identified 280–381 differentially expressed genes between microporous architectures, with over half being non-coding RNAs, suggesting an important role for post-transcriptional regulation. Enrichment analyses indicated modulation of pathways involved in immune activity, ossification, calcium signaling and autophagy. Immunohistochemistry confirmed similar inflammatory mechanisms across both macroarchitectures but revealed earlier M1-to-M2 macrophage transition and faster inflammatory resolution with the finest porous network.ConclusionThis integrative in vivo model provides a robust workflow for correlating structural, cellular, and molecular dimensions of bone regeneration within the same specimen. The findings show that scaffold macroarchitecture influences both the extent and timing of immune and osteogenic processes. While scaffolds with 250 μm and 500 µm pores supported regeneration, the finer design consistently promoted more advanced tissue formation and maturation. These results underscore the key role of scaffold design in modulating bone healing and highlight this model as a platform for studying structure–function relationships in bone tissue engineering.

Introduction: Intensive Care Units (ICUs) provide advanced, evidence-based care for critically ill patients. Physiotherapy is a vital component of ICU care but is often unavailable or insufficiently standardized. This study examined physicians’ and nurses’ satisfaction with physiotherapy care in Croatian ICUs and identified potential areas for improvement. Methods: A 26-item digital questionnaire was disseminated throughout Croatian ICUs to physicians and nurses. The items addressed included physiotherapy availability, equipment accessibility, satisfaction with the quality and effectiveness of care, and their perspectives on improvement. Responses were rated on a 5-point Likert scale or by selecting predefined options. Data analysis was performed using descriptive statistics in R Studio. Results: In total, 120 participants from 12 Croatian counties were included. The majority of responses (105) were from nurses/technicians, and only 15 from physicians. Physiotherapists were available in all ICUs, mainly on a consultative basis and mostly during morning shifts. Participants reported that physiotherapy interventions were effective in reducing pain, improving joint mobility, and enhancing respiratory function. Despite high overall satisfaction, participants emphasized the need for extended physiotherapist availability, improved ICU-specific training, and greater professional autonomy. Conclusion: Physicians and nurses expressed general satisfaction with ICU physiotherapy care but suggested improvements in physiotherapy availability and staff competence. Implementing standardized physiotherapy practices across ICUs could improve treatment outcomes and contribute to earlier patient discharge.

Objectives The 1st Global Consensus for Clinical Guidelines (GCCG) in Implant Dentistry introduced an innovative, evidence-based approach to developing patient-centered and practical recommendations for the rehabilitation of the edentulous maxilla. Within this framework, Group 1 aimed to formulate clinical recommendations on the number of implants required, timing of implant placement, and timing of loading. Materials And Methods Group 1 followed the S2k-level guideline framework of the Association of the Scientific Medical Societies in Germany (AWMF), using a structured nominal group technique. The evidence base included three systematic reviews evaluating clinician-reported outcomes (ClinROs) and patient-reported outcomes (PROs), supplemented by structured single-round international surveys involving expert clinicians, patients, and cross-disciplinary experts. Survey content covered diagnostics, treatment planning, clinical procedures, and maintenance care. Draft recommendations were discussed during the in-person consensus meeting in Boston (June 16-18, 2025) and finalized through anonymous plenary voting. Consensus was defined as ≥ 75% and ≤ 95% agreement and strong consensus as &gt; 95% agreement. Results Group 1 formulated 12 clinical recommendations across the workflow domains of diagnostic tools, treatment planning, and treatment procedure. During plenary voting, three of these recommendations reached strong consensus, and nine achieved consensus. The number of voters per recommendation ranged from 61 to 90, with an average of 83. Conclusions This consensus report provides structured, evidence-based recommendations on implant number, placement timing, and loading protocols for rehabilitation of the edentulous maxilla. These guidelines are intended to support individualized, patient-centered care while also identifying priority areas for future research.

Peri-implantitis is a biologic complication of implant therapy that compromises long-term function and esthetics. With obesity rising globally, determining whether body mass index (BMI) independently contributes to peri-implantitis is critical for identifying at-risk patients and improving implant success. The purpose of this study was to measure the association between BMI and peri-implantitis. This was a retrospective cohort study of implants placed at the Philadelphia Veterans Authority Medical Center between 2006 and 2019. Patients were included in the study if they had complete medical and dental records and a BMI recorded within 3 months of placement. Patients with systemic confounders such as bisphosphonate therapy, head and neck radiation, or incomplete data were excluded. The primary predictor variable was BMI, which was utilized as a binary variable as either nonobese (<30 kg/m2) or obese (≥30 kg/m2). The outcome was time from implant placement to peri-implantitis, defined as radiographic evidence of crestal bone loss with clinical bleeding on probing, with or without suppuration. Covariates included age, sex, diabetes status, smoking history, alcohol use, implant location, and prior bone grafting. Kaplan-Meier curves were constructed for each predictor, and time-to-event curves were compared with log-rank tests to identify significant predictors of peri-implantitis. Multivariate analysis of significant predictors was performed using Cox proportional hazard models to estimate adjusted hazard ratios. Statistical significance was set at P < .05. Our database included 325 subjects who received 1,138 implants. Utilizing a subject-level analysis, 325 implants (28.6%) composed the final study sample after randomly selecting 1 implant per subject. The mean subject age was 59.3 ± 10.6 years, and 310 (95.4%) of subjects were male. Peri-implantitis occurred in 80 implants (24.6%). The 5-year peri-implantitis rates were 22.7 and 34.0% for subjects with BMI<30 kg/m2 and BMI≥30 kg/m2, respectively (P = .04). In the multivariable Cox proportional hazards model, BMI ≥ 30 kg/m2 remained independently associated with an increased risk of peri-implantitis (hazard ratio, 1.56; 95% CI, 1.00 to 2.44; P = .04). Elevated BMI is an independent predictor of peri-implantitis. These findings emphasize the need for integrating BMI and metabolic screening into implant planning and maintenance. Recognition of obesity-related inflammatory mechanisms may improve preventive strategies and long-term implant outcomes in clinical practice.

Guided bone regeneration (GBR) relies on barrier membrane integrity to prevent soft-tissue ingrowth. Although collagen membranes are widely used, their limited longevity can compromise space maintenance, underscoring the need for strategies that enhance membrane stability without impairing the regenerative potential. We hypothesized that thermal denaturation of platelet-poor plasma (PPP), combined with heat-induced modifications of collagen fibrils, could generate a volume-stable, plasma-rich composite that preserves membrane structure and restricts cellular penetration. To test this proof-of-principle concept, collagen membranes were soaked in PPP and either kept at room temperature or subjected to thermal treatment (75 °C/10 min) prior to implantation in rat calvarial defects. Bone regeneration and membrane behavior were evaluated after three weeks using micro-computed tomography (micro-CT) and histology. Micro-CT suggested only minor numerical differences in mineralized tissue between groups; however, these data should not be overinterpreted because micro-CT cannot differentiate mineralization formed within the collagen membrane from mineralization adjacent to it. Consistent with this limitation, histology demonstrated that mineral deposition and early bone formation extended into the structure of room-temperature PPP membranes, whereas mineralized tissue in the thermally treated group was predominantly located outside the membrane, indicating reduced osteoconductive integration within the membrane. Together, these findings support that thermal denaturation of PPP shifts early composite membrane behavior toward barrier-dominant characteristics at the expense of intramembranous mineralization.