Skin wound infections persist through a self-reinforcing "infection-inflammation" cycle that compromises tissue repair. Here, we demonstrate that surface chirality of nanomaterials serves as an independent parameter to disrupt this loop through targeted metabolic interference. Using gold nanoparticles (GNPs) as a model, we show that D-chiral GNPs (GNP-D) exhibit superior efficacy over their L-enantiomers (GNP-L) in repressing bacterial basal metabolism and impeding near-surface motility. Integration of transcriptomic profiling and molecular dynamics identifies the mannitol-specific phosphotransferase transporter MtlA as a pivotal target, where GNP-D induces enhanced structural perturbations at functional residues compared to GNP-L. In a murine infection model, GNP-D significantly reduces bacterial burden and accelerates wound closure while repolarizing the wound microenvironment from a persistent pro-inflammatory state toward a pro-resolving and regenerative phenotype. Notably, genetic ablation of mtlA abrogates the chiral bias across all metabolic and immune readouts, providing evidence that this advantage is mediated via the MtlA/PTS axis. These results establish a "chirality-membrane-protein coupling" framework for the rational design of targeted antimicrobial and immunomodulatory nanomedicines.

OBJECTIVES:This multicenter prospective cohort study follows a 1-year period after a previously published randomized controlled trial, comparing the radiographic and clinical outcomes of implants placed with simultaneous guided bone regeneration (GBR) using bioceramic (BC) versus xenograft (BO). MATERIALS AND METHODS:Patients from the previous trial were recalled 1 year after crown delivery. The follow-up data focused on the buccal bone stability evaluated by CBCT and implant survival rate, Probing Depth (PD), Bleeding on Probing (BOP), Plaque Index (PI), and patient satisfaction through Oral Health Impact Profile-5 (OHIP-5). RESULTS:Out of 150 enrolled patients in a previous trial, a total of 97 patients completed the 1-year follow-up: 44 in the BC group and 53 in the BO group. The implant survival rate was 100% in both groups. Change in horizontal buccal bone thickness (△HBBT) at 1 year post-crown delivery versus immediately post-surgery was -0.28 ± 0.10 mm for the BC group and -0.91 ± 0.09 mm (mean ± standard error) for the BO group, with the BC group exhibiting less bone resorption along the implant than the BO group (p = 0.0000). No significant differences were observed in PI, BOP, or PD. Patient satisfaction remained high in both groups. CONCLUSIONS:GBR with bioceramic demonstrated stable radiographical bone on the buccal side of the implant 1 year after crown delivery.

AIM:Platelet-rich fibrin (PRF) has been widely utilized in oral and craniofacial tissue regeneration owing to its autologous origin and favorable biological properties. However, the limited structural stability of conventional PRF restricts its space-maintaining capacity and osteogenic performance in guided bone regeneration (GBR). To address these shortcomings, a novel heat-modified PRF (Heat-H-PRF) was developed to improve the structural stability and osteogenic performance of PRF. METHODS:Human PRF was subjected to brief thermal treatment to generate Heat-H-PRF. Material microstructure was examined by scanning electron microscopy. In vitro biocompatibility and osteogenic potential were assessed using MC3T3-E1 preosteoblasts through analyses of cell adhesion, proliferation, alkaline phosphatase activity, matrix mineralization, and osteogenic marker expression in comparison to a commercially available collagen membrane. Bone regeneration was also evaluated in vivo using a murine critical-size calvarial defect model, with micro-computed tomography, histological staining, and immunohistochemical analysis performed at 4 weeks post-implantation. RESULTS:Heat-H-PRF demonstrated excellent cytocompatibility and significantly enhanced osteoblast-lineage cell proliferation, spreading, osteogenic differentiation, and mineralized matrix formation in vitro compared with collagen membrane. In a murine calvarial defect model, Heat-H-PRF resulted in significantly greater new bone volume, bone surface, and collagen deposition, accompanied by stronger expression of osteogenic markers Runx2, Osterix, osteocalcin, and collagen 1. Furthermore, the improved structural integrity of Heat-H-PRF suggests enhanced handling stability and potential space-maintaining properties, which may contribute to improved bone regeneration. CONCLUSION:Heat-modified PRF represents a simple and autologous biomaterial with improved handling properties and enhanced osteogenic potential. These findings suggest that Heat-H-PRF may serve as a promising adjunctive membrane-like scaffold for guided bone regeneration.

Implant dentistry, as a relatively young field in dental medicine, has seen significant growth in research over the past decade. This article reviews the recent developments in implant dentistry by focusing on 3 key aspects: the current state of research, the reliability and reporting quality of evidence, methodological and statistical limitations, and additional factors shaping clinical decisions. Despite the increasing volume of studies, the quality and methodology of research remain inconsistent, and reporting bias continues to distort the evidence base. High-level evidence, such as randomized controlled trials (RCTs) and systematic reviews, is essential for clinical decision-making; however, reporting bias remains a persistent issue. Furthermore, the increasing reliance on digital platforms for academic dissemination has both enhanced the accessibility of research and introduced new challenges regarding accuracy, transparency, and commercial influence. The article also highlights the need for improvements in reporting standards, development of core outcome sets, and prevention of reporting bias to strengthen the reliability of evidence in implant dentistry. This article aims to provide a comprehensive overview of the state of evidence-based implant dentistry and offer insights into its future development.

Background/Objectives: Adequate peri-implant soft tissue thickness is essential for long-term peri-implant health and esthetics. Horizontal platelet-rich fibrin (H-PRF) has been proposed to support soft tissue regeneration; however, experimental and translational evidence for its application in peri-implant soft tissue augmentation remains limited. This study aimed to evaluate a H-PRF membrane block approach primarily through an experimental animal model, with clinical cases presented to illustrate translational feasibility. Methods: A customized compression device was used to fabricate the H-PRF membrane block. The biological performance of the H-PRF membrane block was first evaluated in a rabbit model, with histologic assessment of peri-implant soft tissue thickness and integration at 8 weeks. Representative clinical cases requiring peri-implant mucosal thickening were subsequently treated with H-PRF membrane block on the buccal aspect of the alveolar bone beneath a supra-periosteal flap to demonstrate clinical applicability. Results: In the animal model, the H-PRF membrane block resulted in a significant increase in peri-implant soft tissue thickness by increasing the lamina propria compared with control sites demonstrated by histologic analysis. The clinical illustrations showed stable buccal soft tissue volume and contour with minimal patient morbidity. Conclusions: Within the limitations of this experimental study, the horizontal H-PRF membrane block technique demonstrated promising biological performance for peri-implant soft tissue augmentation in an animal model. The accompanying clinical illustrations support the translational feasibility of this approach. Clinical relevance: This experimental study provides biological and translational insight into a minimally invasive strategy for peri-implant soft tissue thickening and may inform future controlled clinical investigations.

Failure to maintain the epithelial seal at the tooth-gingiva interface drives periodontitis. This specialized junctional epithelium (JE) is critical for immune homeostasis, yet mechanisms for its regeneration are poorly understood. Using murine gingivectomy, single-cell transcriptomics, lineage tracing, and clinical data, we delineate requirements for JE repair. We identify ODAM as a specific JE marker derived from Krt5+ basal progenitors. We show these cells migrate from distal sites, explaining the superior outcomes of progenitor-preserving single flap surgery. Genetic deletion of p63 blocks JE regeneration and disrupts cellular organization. We define an essential p63-RUNX1-ODAM axis for JE specification, distinct from the p63-KLF4-loricrin pathway driving keratinization-a feature of pathological repair. These findings reveal a fundamental molecular switch controlling epithelial fate, offering a roadmap to therapeutically promote tissue sealing at inflammation-prone interfaces.

BACKGROUND:Extracellular vesicles (EVs), especially exosomes, are nanoparticles increasingly recognized as key regulators of intercellular communication in both physiological and pathological aspects. Despite rapid progress, inconsistencies in nomenclature, isolation, and characterization continue to restrict translational advancement. This review aims to offer a comprehensive synthesis of EV biology, with a focus on biogenesis, molecular composition, heterogeneity, and methodological considerations for isolation and characterization. METHODS:A narrative review of the literature was performed, assessing historical progress, molecular mechanisms regulating EV biogenesis and payload selection, and existing experimental methods for EV isolation and analysis. Moreover, a comparative analysis of classical and emerging isolation approaches was conducted. RESULTS:EVs are shown to carry diverse bioactive cargo, such as proteins, lipids, and nucleic acids, allowing modulation of cascades implicated in immunity, tissue regeneration, and disease progression. Considerable variability exists across EV subpopulations, complicating categorization and functional attribution. Isolation techniques demonstrate unique trade-offs between scalability, yield, purity, and functional integrity, with no universally optimal strategy. Crucially, methodological selection is highly based on downstream applications, with therapeutic and diagnostic uses necessitating fundamentally varying performance criteria. CONCLUSION:EVs serve as dynamic signaling systems with significant therapeutic and diagnostic potential. Advancing the discipline needs standardized techniques, enhanced classification platforms, and context-specific optimization of isolation approaches. A deeper comprehension of EV biology and methodological rigor will be necessary to unravel their full application in precision medicine.

BACKGROUND:Despite successful reduction of bacterial load and clinical inflammation following periodontal therapy, high recurrence rates indicate that prior infections induce lasting host alterations, maintaining latent disease susceptibility AIM: This review elucidates the biological basis of periodontal recalcitrance through innate immune memory (trained immunity), examining durable functional reprogramming at both local and systemic levels. MATERIALS AND METHODS:We comprehensively searched PubMed/MEDLINE and Scopus databases for peer-reviewed literature published primarily within the last decade (up to 2026). The search strategy utilized combinations of terms including "periodontitis", "trained immunity", "epigenetic reprogramming", "bone marrow axis", and "clonal hematopoiesis". Mechanistic, multi-omics, and clinical data were evaluated and synthesized, focusing on local resident cell reprogramming, ectopic lymphoid organogenesis, the periodontium-bone marrow axis, and clonal hematopoiesis. RESULTS:Current evidence supports the existence of a multi-level immunological imprint. Locally, gingival fibroblasts and resident immune cells acquire stable epigenetic modifications and undergo glycolytic shifts. These changes lower their activation thresholds, generating a hyper-responsive microenvironment sustained by Tertiary Lymphoid Structures. Systemically, periodontal inflammation transmits endocrine signals (IL-1β, type I interferons) to hematopoietic stem and progenitor cells. This central adaptation biases myeloid differentiation and establishes heritable epigenetic priming, accelerating the output of hyper-reactive neutrophils. Additionally, age-related Clonal Hematopoiesis of Indeterminate Potential (CHIP) amplifies this inflammatory dysregulation. CONCLUSIONS:Periodontitis recurrence is fundamentally driven by maladaptive immunological memory. This persistent state is encoded via epigenetic and metabolic reprogramming within local tissues and central hematopoietic niches, exacerbating destruction upon microbial restimulation. CLINICAL RELEVANCE:Achieving true biological resolution in periodontitis requires a paradigm shift from solely controlling the biofilm to incorporating targeted host-modulatory therapies that resolve these maladaptive epigenetic and metabolic adaptations.

INTRODUCTION:Platelet-rich fibrin (PRF) has been commonly utilized for ridge preservation techniques either to introduce supraphysiological concentrations of autologous growth factors to the defect area (typically when mixed within a bone graft) or utilized alone as a solo "barrier" membrane. Noteworthy, however, one of the commonly reported drawbacks of PRF is its relatively short resorption period characterized by lasting roughly 2 weeks. This may therefore be insufficient for complete soft tissue closure and/or preventing soft tissue cells from infiltrating into the bony compartment. Recently, it was discovered that by heating plasma and denaturing albumin using the Bio-Heat technology, the resorption properties of PRF could be extended from a standard 2-3 week period toward 4-6 months. The aim of the present human case series was to investigate for the first time the safety and applicability of utilizing this novel 100% autologous extended-PRF (e-PRF) membrane for ridge preservation. MATERIALS AND METHODS:Twenty-two patients requiring 22 single tooth posterior extractions were included in this case series. In all cases, atraumatic extractions were performed, and the sites were grafted using a combination of bone allograft and standard PRF to create "sticky bone." Noteworthy, the barrier membrane utilized over top of the bone graft was the novel e-PRF, which was utilized as a solo membrane in place of standard collagen or polytetrafluoroethylene (PTFE) membranes. Cone-beam computed tomography scans were taken immediately after extractions and at 3 months postoperatively. Ridge width at 1, 3, and 5 mm apical to the crest, and buccal and lingual height dimensions were recorded at both time intervals. Additionally, buccal bone thickness at 1, 3, and 5 mm apical to the crest was recorded at baseline. RESULTS:All extraction sites healed uneventfully without any postoperative complications. No clinical signs of infection or other complications were detected. The mean change in ridge width at 1, 3, and 5 mm apical to the crest was -1.27 ± 0.70, -0.94 ± 0.80, and -0.69 ± 0.79 mm, respectively. The mean change in buccal height and lingual height was -1.25 ± 1.16 and -0.94 ± 1.07 mm, respectively. CONCLUSIONS:The use of e-PRF membranes in place of collagen membranes for ridge preservation was shown to be an effective, safe, and predictable treatment modality. The e-PRF membranes can be fabricated at low cost with a barrier function that resorbs much more slowly over time when compared to standard PRF membranes. While this preliminary report demonstrated successful outcomes, additional randomized controlled clinical trials investigating soft tissue outcomes of the e-PRF membranes when compared to more conventionally utilized membranes are further necessary to support these novel findings. CLINICAL RELEVANCE:The use of e-PRF membranes in ridge preservation is a safe, predictable, and all-natural alternative to traditional membranes.

The treatment of osteomyelitis, a deep-tissue bacterial infection, remains challenging due to antibiotic resistance and impaired bone regeneration. Herein, the authors report a near-infrared (NIR)-photoresponsive nitric oxide (NO) nanotherapeutic platform (RSNO-VP/Ti3C2) constructed from a violet phosphorus (VP)/Ti3C2 van der Waals heterostructure and an S-nitrosothiol (RSNO) NO donor. This platform utilizes the photothermal effect of the heterostructure under 808 nm NIR irradiation to precisely trigger and control NO release from RSNO, enabling a synergistic mild photothermal and NO gas therapy. The RSNO-VP/Ti3C2 composite demonstrates potent antibacterial efficacy against both Staphylococcus aureus (99.51%) and Escherichia coli (96.11%), effectively eradicates biofilms, and exhibits enhanced environmental stability (degradation time constant tau = 19.31 days). Its biocompatible degradation products, phosphate ions and nano-TiO2, support osteogenic differentiation. In a murine osteomyelitis model, NIR-triggered RSNO-VP/Ti3C2 treatment effectively clears bacteria, alleviates inflammation, and promotes significant bone repair. This work presents a promising non-antibiotic strategy for comprehensive osteomyelitis therapy.

AIM:To compare the impact of intraoral scanning (IOS) and cone-beam computed tomography (CBCT) registration on implant positional accuracy in robotic computer-assisted implant surgery (r-CAIS). MATERIALS AND METHODS:Patients requiring implant placement in the anterior or premolar regions were enrolled and randomly allocated to either a CBCT group or an IOS group at a 1:1 ratio. Implant positional accuracy was assessed by comparing planned versus actual implant positions using global platform deviation, global apex deviation and angular deviation. Subgroup analyses were performed based on jaw position and span length. The implant survival rate and patient satisfaction were recorded at prosthesis delivery. Statistical analysis was performed using linear mixed-effects modelling. RESULTS:Thirty-two patients were included (16 patients with 25 implants in each group). In the IOS group, the global platform deviation, global apex deviation and angular deviation were reported as mean ± standard deviation (SD): 0.89 (0.65) mm, 0.95 (0.77) mm and 1.91 (1.98)°, respectively. In the CBCT group, the corresponding values were 0.88 (0.42) mm, 0.98 (0.46) mm and 1.84 (1.46)°. No statistically significant differences were found between IOS and CBCT groups (p > 0.05) regardless of jaw position or edentulous span. The implant survival rate and patient satisfaction were 100% in both groups. CONCLUSIONS:Preoperative registration using IOS is non-inferior to CBCT-based registration in implant accuracy for r-CAIS, supporting its application as a radiation-free alternative for registration in partially edentulous patients with sufficient number of stable residual teeth. TRIAL REGISTRATION:ChiCTR2400093045.

BACKGROUND:Diabetic wounds signify a major complication of diabetes mellitus, characterized by chronic inflammation, compromised angiogenesis, and high risk of infection, amputation, and mortality. Contemporary therapies remain limited in efficacy and durability. This review aimed to comprehensively assess exosome-mediated interventions as a cell-free regenerative approach for diabetic wound healing. METHODS:This narrative-scoping review was conducted using PubMed, Scopus, Web of Science, EMBASE, and Cochrane databases, identifying 176 preclinical and clinical studies. Included studies evaluated exosome origins, mechanisms of action, delivery platforms, and treatment outcomes in diabetic wound healing. RESULTS:Exosomes derived from mesenchymal stem cells, progenitor cells, blood products, immune cells, and natural sources consistently improved wound healing by enhancing angiogenesis, re-epithelialization, fibroblast proliferation, and extracellular matrix remodeling, while decreasing oxidative stress and chronic inflammation. Mechanistically, these effects were regulated via the stimulation of the PI3K/AKT, ERK/MAPK, STAT3, HIF-1α/VEGF, and Nrf2 signaling, together with the suppression of the AGE/RAGE-regulated ferroptosis and apoptosis. Biomaterial-based delivery systems, including scaffolds, microneedle patches, and hydrogels, significantly enhanced exosome retention, stability, and treatment efficacy. Across studies, exosome treatments showed expedited wound closure, enhanced collagen deposition, and improved vascularization in diabetic models. CONCLUSION:Exosome-mediated therapies represent a promising and multifaceted regenerative strategy for diabetic wound healing, addressing pivotal pathophysiological deficits. Nevertheless, challenges associated with standardization, scalability, and clinical validation must be resolved before widespread clinical application.

Diabetes-induced osteoporosis significantly elevates the risk of fracture-related disability and mortality. Developing effective therapeutic strategies for diabetic-related bone defects has become a pressing concern in both clinical and research domains. This study innovatively constructs a near-infrared light-responsive (NIR) intelligent hydrogel system (carboxymethyl chitosan/gelatin/black phosphorus@bFGF, CG/BPb), utilizing carboxymethyl chitosan and gelatin as the matrix while integrating polydopamine (PDA)-functionalized black phosphorus nanosheets (BP@PDA) as a controlled-release carrier for basic fibroblast growth factor (bFGF). The CG/BPb hydrogel demonstrated remarkable mechanical strength (up to 25 kPa compressive stress at 55

OBJECTIVES:Adequate horizontal bone width is essential for successful implant placement and long-term stability. This study aimed to compare the outcomes of two techniques for horizontal alveolar ridge augmentation: the horizontal platelet-rich fibrin (H-PRF) bone block technique and the Sausage technique. MATERIALS AND METHODS:Fifty patients, presenting 63 tooth sites, were enrolled between 2023 and 2025. Twenty five patients were treated with H-PRF bone block technique (H-PRF group), while 25 patients were treated using the "Sausage" technique (Sausage group) for horizontal bone augmentation. The bone width gain, bone stability rate, and bone volume change at 6 months after surgery were quantified by measurements through cone beam computed tomography (CBCT) scans. Furthermore, the correlation between bone width gain, bone stability rate, and gender, defect site, and bone defect type was analyzed. The complication rates were also recorded. RESULTS:The H-PRF group demonstrated significantly greater horizontal bone gain at the crestal level compared with the Sausage group (0 mm level: 2.85 ± 4.05 mm vs. 0.79 ± 2.35 mm; p = 0.043), while no significant differences were observed at 2, 4, 6, 8 mm levels (p > 0.05). The bone stability rate was 63.21% ± 27.67% for the H-PRF group and 63.88% ± 16.64% for the Sausage group (p = 0.791). Both bone width gain and bone stability rate were not associated with gender or defect site. However, defect type showed a significant association with horizontal bone width gain at the most apical levels (6 and 8 mm). CONCLUSIONS:The H-PRF bone block technique achieved comparable bone augmentation outcomes to the Sausage technique; this technique represents a promising approach that may be considered for horizontal bone augmentation.

During homeostasis, osteocyte apoptosis is typically associated with bone loss through enhanced osteoclast recruitment and bone resorption. However, whether apoptotic osteocytes also regulate bone formation remains elusive. Here we report that conditional deletion of Mdm2, an E3 ubiquitin ligase regulating cell survival, causes osteocyte apoptosis but paradoxically results in a marked increase in bone mass attributed to up-regulated osteogenic activity. Single-cell RNA sequencing reveals enhanced osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) in conditional knockout mice, with enrichment of cellular calcium related pathways. Mechanistically, apoptotic vesicles (apovs) from Mdm2-deleted osteocytes are engulfed by BMSCs. TRPM8, a calcium channel protein, is enriched in osteocyte-derived apovs and transported into BMSCs, thereby promoting osteoblastic differentiation. Additionally, pharmacological inhibition of TRPM8 attenuates the high bone mass phenotype in conditional knockout mice. Therefore, Mdm2 deletion in osteocytes leads to osteocyte apoptosis, which enhances bone formation through communicating with BMSCs via TRPM8-enriched apovs. Our findings underscore the pivotal role of osteocytes in bone homeostasis and unveil a previously unrecognized mechanism whereby osteocyte apoptosis stimulates osteogenesis through affecting the fate of BMSCs in a TRPM8-mediated paracrine mechanism.

BACKGROUND:The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly increasing with high risk to develop cirrhosis, hepatocellular carcinoma (HCC) and other end-stage liver diseases. However, only two drugs, resmetirom and semaglutide, have been approved by the US food and drug administration (FDA) for the treatment of MASLD, with relative low efficient and obvious side effects. Nanomaterials emerged with constantly growing availability of disease therapy benefiting from their well biocompatibility and appropriate properties. OBJECTIVE:The aim of our present study is to identify and fabricate new nanoparticles with high clinical translational potential for MASLD therapy. DESIGN:We systematically screened biocompatible nanoparticles for anti-MASLD capacities in vitro by evaluating their regulatory effects on perilipin-2 (PLIN2), the key molecule in lipid droplet (LD) formation and stability. The exact effects and molecular mechanisms of the identified nanoparticle on MASLD were explored in both cellular and animal models. RESULTS:We identified a carboxyl fullerene derivative, named four malonate groups-substituted C70 fullerene (QF70), as the most potent candidate for MASLD therapy. Notably, QF70 could facilitate lysosomal degradation of PLIN2. More importantly, oral administration of QF70 robustly blocked both diet-induced and leptin deficiency-induced MASLD development with significant improvement in obesity and insulin resistance. We further validated the clinical application potential of QF70 in MASLD-related metabolic disorders in a non-primate model. CONCLUSIONS:This study provides proof-of-concept supporting a nanoparticle-based agent as a LD homeostasis-targeted therapeutic to treat MASLD and related metabolic diseases.

Osteoblasts orchestrate the infiltration and crystallization of mineral precursors within collagen fibrils. Certain osteoblast-secreted mineralization-inducing proteins further stimulate bone formation. In this study, scRNA-seq analysis of murine skull and long bone revealed a striking expression pattern of carbonic anhydrase III (Car3) in osteoblasts. We uncovered a pivotal role for CAR3 in osteoblast lineage cells, revealing its critical function in skeletal development and homeostasis. Conditional ablation of Car3 in Prx1-lineage cells resulted in osteopenia and markedly impaired osteoblast activity, underscoring its functional role. Mechanistically, the primary transcription factor RUNX2 directly regulated Car3 expression, mediating its spatiotemporal expression during development. Notably, CAR3 promoted collagen intrafibrillar mineralization by forming a ternary complex with COL1A1 and bone sialoprotein (BSP), thereby facilitating mineral deposition. Furthermore, CAR3-functionalized scaffolds significantly improved bone repair and regeneration by promoting both matrix mineralization and recruitment of Prx1-lineage cells. These findings establish CAR3 as a critical coordinator of osteoblast differentiation and collagen interfibrillar mineralization, positioning it as a central mediator for maintaining skeletal integrity and enabling regeneration.

INTRODUCTION:The development of various autologous platelet concentrates (APCs) has garnered recent attention for various applications in tissue regeneration. The aim of this study was to investigate 3 protocols to produce APCs on the biological capacity of human dental pulp cells (hDPCs) cultured under both normal and inflammatory conditions (induced by LPS from E. coli) in vitro. METHODS:HDPCs were cultured in culture media from either (1) platelet-rich plasma (first centrifugation at 900 RCF for 5 minutes and second centrifugation at 2000 RCF for 15 minutes), (2) injectable-platelet-rich fibrin (700 RPM for 3 minutes), or (3) concentrated platelet-rich fibrin (C-PRF) (2000 RCF for 8 minutes) when cultured under normal and inflammatory conditions. Cell migration was assessed using a scratch and transwell assay. Cell proliferation was tested using EdU assay and Ki67 immunofluorescence. HDPCs differentiation was assessed via Alizarin Red Staining, DSPP staining and genes encoding dentin matrix protein 1, dentin sialophosphoprotein, and collagen type I alpha 1. Additionally, hDPCs conditioned under an inflammatory condition were further monitored for genes encoding P65 and interleukin 1 beta. RESULTS:All APC groups demonstrated the ability to promote migration and proliferation with C-PRF demonstrating significantly highest values. Platelet-rich plasma and injectable-platelet-rich fibrin moderately increased mineralized nodule formation and odontogenic marker expression, whereas C-PRF showed the strongest enhancement of Alizarin Red staining and the expression of dentin matrix protein 1, dentin sialophosphoprotein, and collagen type I alpha 1. While culture conditions under inflammatory conditions induced by LPS induced higher interleukin 1 beta, P65, and lower hDPCs differentiation, the use of APCs improved all outcomes and the C-PRF group showed the greatest reduction in negative effects caused by LPS/inflammation. CONCLUSIONS:Based on these findings, the use of APCs was able to improve hDPCs activity in vitro with the C-PRF group showing the best results. Noteworthy, while LPS conditioned media typically led to higher hDPCs inflammation, the use of each APC group, especially C-PRF, was able to attenuate some of this impact. Future large animal and clinical studies are needed to further validate these findings.

OBJECTIVE:To compare the effect of deproteinized bovine bone matrix (DBBM) and horizontal platelet rich fibrin bone block (H-PRF-BB) in transcrestal sinus floor elevation (TSFE). MATERIALS AND METHODS:This retrospective study included 65 patients receiving 73 implants placed simultaneously with TSFE. Patients were divided into two groups: (1) the H-PRF-BB group (23 patients, 24 implants) and (2) the DBBM group (42 patients, 49 implants). Cone beam computed tomography (CBCT) was obtained pre-, immediate post-surgery and at the follow-up time. Residual bone height (RBH), height of the augmented bone above the apex of the implant (AH), and height of the elevated sinus floor (EH) were measured. The differences between the groups were analyzed using Welch's t-test or Mann-Whitney U test. The correlations between RBH0 and whether the implant apex was covered with bone were evaluated through Fisher's exact probability test. RESULTS:RBH preoperative (RBH0) and immediate postoperative (RBH1) exhibited no statistically significant difference between the two groups. The RBH at the follow up time (RBH2) in the H-PRF-BB group (11.46 ± 0.32 mm) was higher than that of the DBBM group (10.31 ± 0.30 mm), but without statistical significance. The bone height gained immediately after TSFE (EH1) was 6.39 ± 0.43 mm in the H-PRF-BB group and 5.65 ± 0.28 mm in the DBBM group (no statistical difference). Nevertheless, the bone height gained at the follow up time (EH2) was higher in the H-PRF-BB (5.39 ± 0.41 mm) group when compared to the DBBM group (4.04 ± 0.24 mm). The bone height change (ΔH) was minimal in the H-PRF-BB group (-1.02 ± 0.18 mm) compared to that in the DBBM group (-1.80 ± 0.23 mm). The mean AH immediately after surgery (AH1) was comparable in both groups, but was higher above the implant apex in the H-PRF-BB group (2.18 ± 0.28 mm) at the follow up time (AH2) when compared to the DBBM group (1.36 ± 0.16 mm). Lastly, the apex exposure rate was also lower in the H-PRF-BB group (12.5%) compared to the DBBM group (29.8%). CONCLUSION:H-PRF-BB showed better radiographic outcomes in TSFE compared to DBBM, with an elevated EH2 and AH2. The use of H-PRF-BB was found to reduce the height decrease over time and lessen implant exposure at the apex.

The amphiphilic balance between cationic and hydrophobic segmentsis a critical determinant of the trade-off between antibacterial activity and biocompatibility of membranolytic polymers. In tertiary amine-based systems, this balance is dynamic and exquisitely sensitive to the pH of the tissue microenvironment. To elucidate the relationship between polymer composition and antibacterial efficacy across a physiological pH range, we developed a library of polymeric proton-gated membranolytic switches (PPGMSs) composed of butyl methacrylate and various tertiary amines. These switches achieve precise, pH-activated antibacterial activity, which is governed by the equilibrium between cationic (protonated amine) and hydrophobic butyl methacrylate and deprotonated amine domains. The switching pH of these switches increases with a higher proportion of tertiary amine or a decrease in higher amine hydrophobicity. From this library, P(E60/B) emerged as a lead compound, demonstrating potent activity againstE. coliandP. aeruginosaunder acidic conditions, and minimal cytotoxicity toward mammalian cells at neutral pH (7.4). Mechanistic studies confirmed bacterial membrane disruption as the mode of action. Crucially, P(E60/B) exhibited significant efficacy in a murine peritonitis model, reducing bacterial loads in a dose-dependent manner. This work establishes PPGMSs as a versatile platform for designing precision antimicrobials that leverage microenvironmental cues for selective therapy.