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Search Results (371)

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Keywords = large bone defect

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24 pages, 1947 KB  
Systematic Review
Clinical Outcomes of Platelet-Rich Fibrin in Endodontic Microsurgery: A Systematic Review and Meta-Analysis
by Carlos Valdivieso del Pueblo, Paloma Montero-Miralles, María León-López, Juan J. Segura-Sampedro, Daniel Cabanillas-Balsera, Jenifer Martín-González and Juan J. Segura-Egea
J. Clin. Med. 2026, 15(16), 6392; https://doi.org/10.3390/jcm15166392 - 18 Aug 2026
Viewed by 278
Abstract
Background/Objectives: Platelet-rich fibrin (PRF) and its derivatives have been proposed as biological adjuncts to enhance tissue healing following endodontic microsurgery (EMS). However, current evidence regarding their effects on postoperative recovery and long-term bone regeneration remains inconsistent. This study aimed to evaluate the efficacy [...] Read more.
Background/Objectives: Platelet-rich fibrin (PRF) and its derivatives have been proposed as biological adjuncts to enhance tissue healing following endodontic microsurgery (EMS). However, current evidence regarding their effects on postoperative recovery and long-term bone regeneration remains inconsistent. This study aimed to evaluate the efficacy of PRF and its derivatives as adjuncts in endodontic microsurgery by separately assessing patient-centered postoperative outcomes and radiographic and volumetric bone-healing outcomes through a systematic review and meta-analysis. Methods: This systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420261400163). Randomized controlled trials and comparative clinical studies evaluating PRF or its derivatives as adjuncts to EMS were eligible. MEDLINE/PubMed, Embase, Scopus, Web of Science, Cochrane CENTRAL, and reference lists were searched from inception to April 2026. Outcomes included postoperative pain, edema, quality of life, clinical–radiographic healing, CBCT volumetric bone regeneration, bone density, and outcomes in complex defects. Risk of bias was assessed using RoB 2 and ROBINS-I. Random-effects meta-analyses were performed where appropriate, and certainty of evidence was evaluated using the GRADE approach. Results: Seventeen clinical reports corresponding to sixteen independent datasets were included. PRF and its derivatives improved early postoperative recovery, particularly postoperative pain during the first postoperative week. Meta-analysis demonstrated a significant reduction in early postoperative pain favoring PRF-based interventions (SMD/Hedges g = −0.62; 95% CI, −1.03 to −0.21; p = 0.003). Evidence regarding long-term bone regeneration and clinical–radiographic healing remained heterogeneous and inconclusive. CBCT-based studies suggested accelerated early bone healing, although no consistent superiority was demonstrated at 6–12 months. The certainty of evidence ranged from moderate for postoperative pain to very low for volumetric bone regeneration. Interpretation of the findings is limited by clinical and methodological heterogeneity and the small number of studies available for several outcomes. Conclusions: The available evidence suggests that PRF may improve early postoperative recovery and soft-tissue healing after endodontic microsurgery. However, current evidence does not support PRF as a predictable substitute for bone grafts or regenerative biomaterials in large or non-contained defects. Well-designed CBCT-based randomized clinical trials with standardized outcome measures are needed. Full article
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9 pages, 12376 KB  
Case Report
Large Schneiderian Membrane Perforation Repair During Sinus Lift Surgery: A Case Report
by Francisco Correia, Mafalda Azevedo, Marta Costa, Francisca Abreu and Ricardo Faria-Almeida
Complications 2026, 3(3), 14; https://doi.org/10.3390/complications3030014 - 17 Aug 2026
Viewed by 145
Abstract
Background: Maxillary sinus floor elevation is a predictable procedure for implant rehabilitation in the posterior maxilla with reduced residual bone height. Schneiderian membrane perforation is the most frequent intraoperative complication during sinus lift surgery and may compromise graft stability and treatment outcomes. Stabilized [...] Read more.
Background: Maxillary sinus floor elevation is a predictable procedure for implant rehabilitation in the posterior maxilla with reduced residual bone height. Schneiderian membrane perforation is the most frequent intraoperative complication during sinus lift surgery and may compromise graft stability and treatment outcomes. Stabilized collagen membrane techniques have been proposed to manage extensive perforations. Objective: The aim of this study was to describe the management of a large Schneiderian membrane perforation (>10 mm) using a stabilized collagen membrane technique and to evaluate the clinical outcome. Case Description: A 67-year-old male patient (ASA I, non-smoker) with insufficient posterior maxillary bone height underwent lateral window sinus augmentation. During membrane elevation, a large perforation (>10 mm) occurred. A resorbable collagen membrane was adapted and stabilized to isolate the defect and create a contained compartment for graft placement. A xenograft was inserted, and an additional collagen membrane was used to cover the lateral window and stabilized with fixation pins. Primary closure was achieved with tension-free sutures. Results: Healing was uneventful, without sinus pathology or postoperative complications. Radiographic evaluation confirmed graft stability and adequate volume maintenance. Implant placement was successfully performed after 6 months, achieving satisfactory primary stability and favorable clinical outcomes after one year of loading. Conclusion: In this case, the stabilized collagen membrane technique allowed successful management of a large Schneiderian membrane perforation, enabling continuation of sinus augmentation, successful graft containment, and favorable implant rehabilitation outcomes. Full article
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13 pages, 661 KB  
Article
Intraoperative PBM Modulates Osteogenic Activity in Human Jawbone Explants: A Comparative Ex Vivo Translational Study
by Ioan Vlad Grigore, Mariana Păcurar, Ovidiu Pop, Sorana Maria Bucur, Elina Teodorescu, Anca Oana Dragomirescu, Ștefan Milicescu and Alina Ormenișan
Oral 2026, 6(4), 102; https://doi.org/10.3390/oral6040102 - 6 Aug 2026
Viewed by 168
Abstract
Background: Surgical removal of jaw cysts may result in bone defects that compromise local structural integrity and delay spontaneous regeneration. Photobiomodulation (PBM) has been proposed as a minimally invasive intraoperative adjunct capable of modulating osteogenic activity; however, translational evidence derived from freshly harvested [...] Read more.
Background: Surgical removal of jaw cysts may result in bone defects that compromise local structural integrity and delay spontaneous regeneration. Photobiomodulation (PBM) has been proposed as a minimally invasive intraoperative adjunct capable of modulating osteogenic activity; however, translational evidence derived from freshly harvested human jawbone tissue remains limited. Objective: This study evaluated the effects of an intraoperative 980 nm PBM protocol on early osteogenic activity, osteoblast-like cell abundance, morphometric outcomes, and cell viability in primary human jawbone explants obtained during cystectomy. Materials and Methods: A comparative translational ex vivo study was conducted using cortical bone explants harvested from 40 patients undergoing surgical treatment of medium- to large-sized maxillary or mandibular cystic lesions. For each patient, one explant was exposed immediately after harvesting to pulsed 980 nm laser irradiation (20 J total energy; 40 J/cm2 fluence), whereas the paired explant served as an untreated control. Explants were cultured using a primary outgrowth technique and subjected to osteogenic induction for 14 days. Osteogenic activity was evaluated by immunofluorescence staining for alkaline phosphatase (ALPL) and osteocalcin (OCN), followed by confocal microscopy and quantitative morphometric analysis. Cell viability was assessed using a live/dead fluorescence assay. Results: Viable cultures were successfully established from 34 patients (85% experimental yield). PBM-treated explants exhibited significantly greater osteoblast-like cell counts than paired controls (median: 2820 vs. 1525 cells; p < 0.001), together with greater cumulative osteoblastic area (median: 537,028 vs. 325,166 relative units; p < 0.001) and higher osteoblastic area occupancy (median: 19.00% vs. 11.75%; p < 0.001). Immunofluorescence analysis demonstrated qualitatively stronger ALPL and OCN expression in PBM-treated cultures. Cell viability did not differ significantly between paired PBM-treated and control cultures (Wilcoxon signed-rank test, p = 0.18). Conclusions: In this comparative ex vivo model, intraoperative 980 nm PBM significantly enhanced early osteogenic activity and increased osteoblast-like cellular abundance in human jawbone explants while maintaining cellular viability. These findings provide translational support for further investigation of PBM as a biostimulatory adjunct to enhance bone regeneration following cyst surgery. Full article
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44 pages, 1847 KB  
Review
Biochemical and Physicomechanical Cues of Biomaterials Guide Osteogenic Differentiation of Mesenchymal Stem Cells
by Bofeng Pan, Adam Maalal and Dake Hao
Int. J. Mol. Sci. 2026, 27(15), 6753; https://doi.org/10.3390/ijms27156753 - 28 Jul 2026
Viewed by 444
Abstract
Bone regeneration remains a significant clinical challenge, particularly for large or critical-sized defects caused by trauma, disease, or congenital abnormalities. Mesenchymal stem cells (MSCs) have emerged as a promising cell source for bone tissue engineering, with their osteogenic differentiation playing a crucial role [...] Read more.
Bone regeneration remains a significant clinical challenge, particularly for large or critical-sized defects caused by trauma, disease, or congenital abnormalities. Mesenchymal stem cells (MSCs) have emerged as a promising cell source for bone tissue engineering, with their osteogenic differentiation playing a crucial role in bone repair. Biomaterials serve as scaffolds that facilitate MSC-mediated bone regeneration by providing structural support and mimicking the extracellular matrix (ECM). This review explores recent advancements in biomaterials designed to promote MSC osteogenesis through two primary approaches: biochemical and physicomechanical stimuli. Therapeutic agent-loaded scaffolds, incorporating growth factors, small molecules, gene materials, peptides, proteins, and extracellular vesicles (EVs), have been extensively studied for their ability to enhance osteogenic differentiation. However, concerns regarding toxicity, off-target effects, and regulatory limitations have led to increasing interest in biomaterials that utilize physicomechanical cues such as stiffness, viscoelasticity, topography, porosity, and dynamic forces (shear stress, compression, vibration) as alternative or complementary strategies. Furthermore, the synergistic effects of multiple physicomechanical cues are being explored to regulate MSC behavior for promoting bone regeneration. This review discusses current challenges, emerging trends, and future directions in the development of next-generation biomaterials that integrate biochemical and physicomechanical approaches for clinical applications in bone repair and regeneration. Full article
(This article belongs to the Special Issue Tissue Engineering Related Biomaterials: Progress and Challenges)
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22 pages, 3846 KB  
Review
Tissue Engineering for Massive Bone Defects: The Volumetric Scaling Problem and Strategies to Solve It
by Sedeek Mosaid, Yousif Jihad, Mostafa Jihad, Ashok Marudanayagam and Paul Lee
Bioengineering 2026, 13(7), 814; https://doi.org/10.3390/bioengineering13070814 - 16 Jul 2026
Viewed by 582
Abstract
Massive segmental bone defects present significant challenges in orthopaedic and maxillofacial reconstruction. As defect size increases, the disparity between tissue volume and diffusion-limited biological processes becomes more pronounced. This narrative review analyses distinctions between centimetre-scale defects and conventional fractures and evaluates current tissue-engineering [...] Read more.
Massive segmental bone defects present significant challenges in orthopaedic and maxillofacial reconstruction. As defect size increases, the disparity between tissue volume and diffusion-limited biological processes becomes more pronounced. This narrative review analyses distinctions between centimetre-scale defects and conventional fractures and evaluates current tissue-engineering strategies in relation to vascularisation, osteogenesis, mechanical stability, immune response, neural integration, and manufacturability. This review synthesises evidence from scaffold design, cell-based approaches, growth factor delivery, type-H vessel biology, NGF–TrkA signalling, large-animal models, and early clinical translation. Current findings indicate that no single scaffold, cell source, or growth factor can reliably reproduce the coordinated biological and mechanical environment required for durable regeneration of human long bones. The strongest preclinical evidence is derived from ovine tibial models employing medical-grade polycaprolactone/β-tricalcium phosphate composites or mechanobiologically optimised titanium lattices. Human data remain limited to case reports and small early clinical series, including hybrid vascularised flap–scaffold reconstructions. Successful clinical translation will require patient-specific constructs that integrate rapid vascularisation, appropriate load sharing, immune-compatible degradation, infection control, and scalable manufacturing. Until robust comparative clinical evidence emerges, established reconstructive methods will remain the standard of care. Hybrid vascularised scaffold-guided strategies should be regarded as promising translational approaches rather than definitive solutions. Full article
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10 pages, 2186 KB  
Case Report
Accordion Maneuver for Delayed Regenerate Formation Following Pediatric Osteosarcoma Resection: A Case Report and Literature Review
by Abdullah Addar, Mishari Alanezi, Nouf Alabdulkarim, Razan Alshatwi, Fahad Alshayhan and Fahad Alhuzaimi
Reports 2026, 9(3), 217; https://doi.org/10.3390/reports9030217 - 9 Jul 2026
Viewed by 364
Abstract
Background and Clinical Significance: Reconstruction of large segmental bone defects following oncologic resection in pediatric patients remains a major challenge. Although distraction osteogenesis with bone transport is a well-established biological reconstructive option, regenerate formation may be compromised in patients receiving chemotherapy. The [...] Read more.
Background and Clinical Significance: Reconstruction of large segmental bone defects following oncologic resection in pediatric patients remains a major challenge. Although distraction osteogenesis with bone transport is a well-established biological reconstructive option, regenerate formation may be compromised in patients receiving chemotherapy. The accordion maneuver, consisting of alternating cycles of compression and distraction, has been described as a method to stimulate bone regeneration, primarily in association with external fixation systems. However, its use in internal bone transport systems using intramedullary lengthening nails following oncologic resection, particularly in the setting of perioperative chemotherapy, remains rarely reported. Case Presentation: We report a case of a 12-year-old boy with high-grade telangiectatic osteosarcoma of the distal femur who underwent neoadjuvant chemotherapy followed by limb-salvage surgery, resulting in a 14 cm segmental bone defect. Reconstruction was performed using plate-assisted bone transport with a motorized intramedullary magnetic nail. During distraction osteogenesis, delayed and asymmetric regenerate formation developed. An accordion maneuver was subsequently initiated, resulting in progressive improvement in regenerate density and corticalization without the need for revision surgery. Conclusions: This case highlights the successful application of the accordion maneuver using internal bone transport following oncologic resection. It represents a minimally invasive technique to stimulate bone healing and may reduce the need for revision surgery; however, larger series are needed to confirm this potential benefit, particularly in biologically compromised patients receiving chemotherapy. Full article
(This article belongs to the Section Orthopaedics/Rehabilitation/Physical Therapy)
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11 pages, 600 KB  
Article
Impact of Metal Artifact Reduction on the Diagnosis of Peri-Implant Defects Around Zirconia and Titanium Implants: A CBCT Pilot Study
by Mahsa Moannaei, Mojdeh Mehdizadeh, Farnaz Mirrashidi, Mohammad Hossein Manouchehri, Sepehr Naghdi, Amirhossein Moaddabi, Nima Malek Hosseini, Gianrico Spagnuolo, Francesco Giordano and Parisa Soltani
Oral 2026, 6(4), 83; https://doi.org/10.3390/oral6040083 - 3 Jul 2026
Viewed by 457
Abstract
Background/Objectives: Metal artifacts from dental implants degrade CBCT image quality and may impair detection of peri-implant bone defects. Zirconia implants produce stronger artifacts than titanium due to its higher atomic number. This study evaluated the impact of a native MAR algorithm (SMARF) [...] Read more.
Background/Objectives: Metal artifacts from dental implants degrade CBCT image quality and may impair detection of peri-implant bone defects. Zirconia implants produce stronger artifacts than titanium due to its higher atomic number. This study evaluated the impact of a native MAR algorithm (SMARF) on CBCT detection of buccal fenestration and dehiscence of varying sizes adjacent to zirconia versus titanium implants. Methods: In this ex vivo pilot study, two 4 mm × 12 mm implants (one titanium and one zirconia) were implanted in a dry human mandible. Artificial fenestration and dehiscence defects were created at the buccal surface of right and left premolar regions, in three sizes (small 2 mm × 2 mm× 1 mm; medium 2 mm × 4 mm× 1 mm; large 2 mm × 6 mm× 1 mm). Scans were acquired with a Papaya 3D (Genoray) CBCT using a single-tooth FOV (4 cm× 4 cm × 5 cm), 83 kVp, 10 mA, 0.1 mm voxel; each condition was imaged with MAR on and off (six repeats each). Two trained observers scored defect presence on a five-point Likert scale. Sensitivity, specificity, inter- and intraobserver agreement (Cohen’s kappa), and comparisons across conditions were calculated. Results: Interobserver κ = 0.65 (substantial); intraobserver κ = 0.87–1.00 (excellent). For titanium implants, sensitivity and specificity were 100% across all defect types, sizes, and MAR settings. For zirconia implants, fenestration sensitivity with MAR off increased with size (small 50%, medium 75%, large 100%); MAR on raised sensitivity to 100% for all sizes, with a significant improvement for small fenestrations (p = 0.005). Dehiscence sensitivity for zirconia was 100% across sizes and MAR conditions. Specificity for zirconia defects was 83.3% with MAR off and decreased to 66.6% with MAR on (p = 0.07). Conclusions: With the Papaya 3D system used in this pilot study, MAR was unnecessary for defect detection adjacent to titanium implants but affected performance for zirconia implants: MAR increased sensitivity for small fenestrations while reducing specificity (although not statistically significant). Clinicians should weigh the sensitivity–specificity trade off when applying MAR around zirconia implants. Full article
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55 pages, 1756 KB  
Review
Patient-Specific Subperiosteal Implants for Oral and Maxillofacial Rehabilitation: A Scoping Review Across Indications, from Established Full-Arch Use to Emerging Single-Tooth and Oncologic Applications
by Luigi Angelo Vaira, Hareem Qadeer, Andrea Biglio, Sebastiano Stellino, Jerome R. Lechien, Antonino Maniaci, Fabio Maglitto, Giuseppe Consorti, Giulio Cirignaco, Carlos Navarro-Cuéllar, Giovanni Salzano, Valentino Vellone, Marco Roy, Javier Herce-López, Marshall M. Freilich, Álvaro Tofé-Povedano, Casper van den Borre, Maurice Y. Mommaerts and Giacomo De Riu
J. Clin. Med. 2026, 15(13), 5220; https://doi.org/10.3390/jcm15135220 - 3 Jul 2026
Cited by 1 | Viewed by 475
Abstract
Background/Objectives: Contemporary patient-specific subperiosteal implants have re-emerged as graftless solutions for oral and maxillofacial rehabilitation, driven by advances in digital planning, CAD/CAM workflows, additive manufacturing, and biomaterial engineering. Their indications have progressively expanded from severely atrophic edentulous jaws to segmental defects, single-tooth replacement, [...] Read more.
Background/Objectives: Contemporary patient-specific subperiosteal implants have re-emerged as graftless solutions for oral and maxillofacial rehabilitation, driven by advances in digital planning, CAD/CAM workflows, additive manufacturing, and biomaterial engineering. Their indications have progressively expanded from severely atrophic edentulous jaws to segmental defects, single-tooth replacement, congenital craniofacial anomalies, salvage situations, and oncologic reconstruction. This scoping review aimed to map the current evidence on modern patient-specific subperiosteal implants, focusing on indications, workflow, design principles, materials, outcomes, complications, and maintenance. Methods: A scoping review was conducted according to PRISMA-ScR principles to identify clinical studies, case series, case reports, systematic and scoping reviews, technical notes, finite element analyses, in vitro studies, and relevant translational investigations dealing with contemporary custom-made or CAD/CAM subperiosteal implants. The evidence was narratively synthesized according to clinical indication and thematic domains, including full-arch rehabilitation, sectional and single-tooth applications, congenital and post-oncologic defects, rescue indications, biomechanics, material selection, surface response, prosthetic protocols, and complication management. No quantitative meta-analysis was performed because of the scoping design and the substantial heterogeneity of study types, indications, implant systems, outcome definitions, and follow-up durations. Results: The final evidence map included 116 records, of which 56 were unique human clinical records with extractable denominators and 60 were biomechanical, in vitro, surface-biology, review, consensus, historical, or conceptual records. Of the 56 unique clinical records, 49 were mapped within the six indication-level clinical sections, while seven were retained as cross-cutting clinical evidence addressing patient-reported outcomes, design-related complications, bone apposition, anchorage strategy, comparative graftless rehabilitation, or reconstructive/prosthetic principles. The six indication-level sections included 52 clinical-record assignments: 15 for full-arch rehabilitation, 13 for segmental or sectional rehabilitation, one for single-tooth rehabilitation, four for congenital or craniofacial indications, 13 for post-oncologic or post-ablative reconstruction, and six for rescue or salvage indications. Because three records addressed more than one indication, these counts represent indication-level assignments rather than mutually exclusive clinical records. Reported survival in most short- to mid-term clinical series was generally high, commonly ranging from 90% to 100%, although lower values of 70–80% were reported in selected longer-term cohorts and survival clearly overestimated clinical success in some studies. Expanding applications include posterior mandibular and maxillary defects, lateral incisor agenesis, cleft-related or syndromic deformities, maxillectomy reconstruction, obturator support, and hybrid rehabilitation with endosseous implants; however, evidence for the indications at the extremes of this spectrum—single-tooth replacement and primary oncologic reconstruction—remains limited to small, largely single-group case series and reports. Soft-tissue events, including dehiscence, mucositis, recession, and framework exposure, were the dominant complications and showed wide variability, with reported recession/exposure rates ranging from approximately 10% in some sectional and full-arch series to as high as 65% in bilateral maxillary cohorts; their clinical significance varied from asymptomatic stable findings to progressive inflammatory complications requiring revision. Conclusions: Patient-specific subperiosteal implants represent a promising and increasingly versatile reconstructive option; however, the present findings should be interpreted as evidence mapping rather than as definitive comparative evidence. Their clinical use should remain highly selective, prosthetically driven, and supported by meticulous planning, rigid fixation, soft-tissue management, and structured maintenance. Standardized success criteria, longer follow-up, and comparative prospective studies are required. Full article
(This article belongs to the Special Issue New Perspective of Oral and Maxillo-Facial Surgery: 2nd Edition)
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15 pages, 1363 KB  
Review
Enhancing Bone Repair Process: Application and Perspective on Photothermal Materials
by Xuchen Yan, Chuanpeng Zhou, Hanyue Mao, Kunlu Lin, Ying Yang, Haoming Liu, Long Liu and Xiaoyan Wang
Molecules 2026, 31(13), 2299; https://doi.org/10.3390/molecules31132299 - 1 Jul 2026
Viewed by 439
Abstract
Repairing large bone defects remains a clinical challenge in orthopedics. Near-infrared (NIR) photothermal therapy (PTT) has recently expanded from high-temperature tumor ablation to the field of mild bone regeneration. Maintaining temperatures within a mild window of 40–42 °C accelerates bone healing by activating [...] Read more.
Repairing large bone defects remains a clinical challenge in orthopedics. Near-infrared (NIR) photothermal therapy (PTT) has recently expanded from high-temperature tumor ablation to the field of mild bone regeneration. Maintaining temperatures within a mild window of 40–42 °C accelerates bone healing by activating osteogenic signals, modulating the immune microenvironment, and providing antibacterial effects. It is important to note that the therapeutic efficacy is highly dependent on the precise control of both temperature and exposure duration: temperatures exceeding 42–43 °C can induce cell apoptosis, while temperatures above 45 °C typically cause necrosis. The reviewed studies employed controlled exposure times (typically 5–15 min per session) to maintain cell viability above 85%, with functional assessments confirming preserved osteogenic differentiation capacity of bone marrow-derived mesenchymal stem cells (BMSCs) and maintained macrophage plasticity after mild photothermal treatment. This performance depends on photothermal conversion materials. This paper reviews the applications of MXene, black phosphorus (BP), polydopamine/graphene oxide (PDA/GO), and metal-based nanomaterials in bone repair. We also analyze photothermal-based immune regulation, sequential repair strategies, and tumor theranostics. Finally, we discuss current challenges and future trends to guide the design of next-generation smart bone repair materials. Full article
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22 pages, 3283 KB  
Review
Integrin Signaling Imbalance in Periodontitis: A Stage-Dependent Link Between Inflammation, Bone Resorption and Regenerative Failure
by Fredy Mardiyantoro, Meircurius Dwi Condro Surboyo, Andari Sarasati and Tetsuya Matsuguchi
Biomolecules 2026, 16(7), 967; https://doi.org/10.3390/biom16070967 - 30 Jun 2026
Viewed by 458
Abstract
Periodontitis is a chronic inflammatory disease driven largely by dysregulated host responses that lead to destruction of periodontal tissues. Integrins are heterodimeric transmembrane receptors that regulate cell adhesion and bidirectional signaling in epithelial cells, immune cells, periodontal ligament fibroblasts, and osteoclasts. During disease [...] Read more.
Periodontitis is a chronic inflammatory disease driven largely by dysregulated host responses that lead to destruction of periodontal tissues. Integrins are heterodimeric transmembrane receptors that regulate cell adhesion and bidirectional signaling in epithelial cells, immune cells, periodontal ligament fibroblasts, and osteoclasts. During disease progression, integrin-related responses may shift across overlapping molecular phases. Epithelial integrins such as α3β1 and α6β4 support barrier integrity, whereas α5β1 may facilitate microbial interaction and inflammatory signaling. β2 integrins and α4β1 contribute to leukocyte recruitment and inflammatory amplification, whereas increased α9β1-associated signaling and reduced αvβ6-mediated regulation of transforming growth factor β (TGF-β) may promote inflammatory persistence. Matrix-associated integrins, including α2β1 and α11β1, support extracellular matrix (ECM) organization and mechanotransduction, whereas αvβ3 cooperates with Receptor activator of nuclear factor kappa B ligand (RANKL) to promote osteoclast activity and alveolar bone resorption. Impaired β1 integrin-dependent signaling and potentially reduced αvβ5-associated efferocytosis may contribute to defective resolution and regeneration. Importantly, integrin expression, activation, and downstream signaling are distinct, and the strength of evidence varies among integrin subtypes. This review proposes a conceptual framework in which periodontitis reflects a dynamic imbalance in integrin-mediated processes that link inflammation, bone resorption, and regenerative failure, rather than being a direct equivalent of clinical periodontal stages or grades. Full article
(This article belongs to the Special Issue New Insights into Integrins: 2nd Edition)
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14 pages, 536 KB  
Review
Advancing Pediatric Radiology Through Artificial Intelligence: Global Progress and Implications for Middle- and Low-Income Countries
by Sana Amreen, Ahmed Khairy, Fakeha Masood, Ngan Chu, Anju Paudel, Abdelrahman Aly Mohamed, Ayantoyinbo Oluwabusayomi and Yossef Alnasser
AI 2026, 7(6), 222; https://doi.org/10.3390/ai7060222 - 16 Jun 2026
Viewed by 860
Abstract
Background: Radiology underpins diagnosis and treatment across pediatrics, yet most artificial intelligence (AI) tools are developed for adults and validated on adult datasets only. Of more than 200 AI systems cleared by the United States (U.S.) Food and Drug Administration (FDA), only about [...] Read more.
Background: Radiology underpins diagnosis and treatment across pediatrics, yet most artificial intelligence (AI) tools are developed for adults and validated on adult datasets only. Of more than 200 AI systems cleared by the United States (U.S.) Food and Drug Administration (FDA), only about 3% include pediatric validation. Because children differ from adults in anatomy, physiology, pathology, epidemiology, and imaging protocols, adult-trained models often perform sub-optimally in pediatric settings. Methods: A narrative review of peer-reviewed literature from 2000 to 2025 was conducted using PubMed, MEDLINE, Google Scholar, and Scopus. Studies involving AI applications in pediatric X-ray, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), echocardiography, and point-of-care ultrasound with quantitative performance metrics were included. Findings were synthesized by imaging modality, clinical task, and differences between high-income countries (HICs) and low- and middle-income countries (LMICs). Results: AI demonstrated strong performance across multiple pediatric imaging tasks. In X-ray interpretation, AI detected fractures with area under the curve (AUC) values up to 0.96 (sensitivity, 90.8%; specificity, 88.7%). Pneumonia classification achieved 76.5% accuracy, and foreign body aspiration detection showed 95.3% specificity in HICs. In ultrasound, AI improved junior sonographers’ detection of intussusception (AUC 0.857 to 0.966) and reduced scan time by more than 50%. AI-assisted bone age estimation achieved a mean error of 0.39 years. In echocardiography, AI-derived ejection fraction showed excellent agreement with experts’ interclass correlation coefficient (ICC 0.983), and AI support improved atrioventricular septal defect detection (84.4% to 86.5%). In MRI, the use of AI enhanced lesion detection and supported quantitative analysis. Deep-learning models trained on routine T1- and T2-weighted sequences predicted liver stiffness across multi-site datasets, while advanced neuroimaging pipelines improved the identification of subtle epileptogenic lesions that are often missed on conventional pediatric MRI. However, adult-trained models showed limited generalizability to children. Still, excluding children under the age of two years improved the reading accuracy of pediatric chest X-rays (CXRs) by adult-trained models from 88% to 97%. AI faces challenges beyond the development of age-specific models. Substantial heterogeneity, limited pediatric-specific datasets, and unresolved medicolegal responsibility further restrict adoption worldwide. Challenges are amplified in LMICs, where unstable electricity, limited radiology resources, weak digital infrastructure, and scarce pediatric providers limit implementation. Additionally, many large language models underperform and lack inclusive algorithms suitable for pediatric radiology in many LMICs. Conclusions: AI can enhance diagnostic accuracy, efficiency, and access to pediatric imaging, particularly in resource-limited settings, through task-shifting and decision support. However, it cannot replace pediatric radiologists as of today. Safe adoption requires pediatric-specific model development, standardized validation metrics, diverse datasets that include LMIC populations, stronger digital infrastructure, robust radiologist training in AI capabilities, and the establishment of clear guidelines and medicolegal policies. Full article
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39 pages, 2710 KB  
Review
Smart Hydrogels for Craniofacial Regeneration
by Hossein Omidian, Erma J. Gill and Umadevi Kandalam
Cells 2026, 15(12), 1054; https://doi.org/10.3390/cells15121054 - 9 Jun 2026
Viewed by 778
Abstract
Hydrogel scaffolds have emerged as instructive microenvironments for craniofacial tissue regeneration, moving beyond passive cell carriers toward platforms that regulate cell fate, vascularization, immune remodeling, and tissue-specific architecture. This review synthesizes hydrogel-associated strategies across dental pulp, periodontal ligament, gingival, bone marrow, jawbone, endothelial, [...] Read more.
Hydrogel scaffolds have emerged as instructive microenvironments for craniofacial tissue regeneration, moving beyond passive cell carriers toward platforms that regulate cell fate, vascularization, immune remodeling, and tissue-specific architecture. This review synthesizes hydrogel-associated strategies across dental pulp, periodontal ligament, gingival, bone marrow, jawbone, endothelial, oral mucosal, induced pluripotent stem cell (iPSC), extracellular vesicle (EV), exosome, secretome, and acellular systems. The evidence indicates that craniofacial hydrogel performance is governed by reciprocal interactions among biological source, scaffold composition, matrix mechanics, spatial architecture, mineral or ionic signaling, growth factor delivery, vesicle-mediated communication, and inflammatory niche modulation. Mineralized and ion-releasing hydrogels most consistently supported osteogenesis and bone repair, whereas extracellular matrix (ECM)-mimetic, peptide, collagen, fibrin, gelatin methacryloyl (GelMA), alginate, hyaluronic acid (HA), and chitosan-based systems enabled pulp–dentin, periodontal, peri-implant, oral mucosal, and soft-tissue reconstruction. Responsive, antimicrobial, antioxidant, conductive, and immunomodulatory hydrogels further expanded the field by targeting diseased microenvironments rather than regeneration alone. Despite strong preclinical evidence, translation remains limited by heterogeneity in scaffold formulations, biological sources, analytical endpoints, defect models, and long-term functional validation. Future progress will require standardized characterization, tissue-specific design criteria, clinically relevant large-animal models, scalable cell-free technologies, and integrated assessment of regeneration, immunity, vascularization, innervation, mechanics, and safety. Full article
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19 pages, 1106 KB  
Review
Vascularized Flaps as Living Bioreactors in Bone Tissue Engineering: From Biological Principles to Translational Strategies—A Narrative Review
by Fabiana Battaglia, Michele Rosario Colonna, Emanuele Cigna, Michele Maruccia and Gabriele Delia
J. Funct. Biomater. 2026, 17(6), 270; https://doi.org/10.3390/jfb17060270 - 1 Jun 2026
Viewed by 549
Abstract
Background: Large segmental bone defects remain a major challenge in reconstructive surgery, particularly in the presence of impaired vascularization. Despite advances in scaffold design and biomaterials, insufficient vascular supply continues to represent the primary limitation in bone tissue engineering, often leading to impaired [...] Read more.
Background: Large segmental bone defects remain a major challenge in reconstructive surgery, particularly in the presence of impaired vascularization. Despite advances in scaffold design and biomaterials, insufficient vascular supply continues to represent the primary limitation in bone tissue engineering, often leading to impaired osteogenesis and graft failure. Objective: This review aims to analyze the role of vascularized flaps as “living bioreactors” in bone tissue engineering, focusing on their capacity to enhance scaffold vascularization, support osteogenesis, and facilitate clinical translation. Methods: A narrative review was conducted through a structured search of PubMed, Scopus, and Web of Science using combinations of the following keywords: “bone tissue engineering”, “vascularized flaps”, “arteriovenous loop”, and “in vivo bioreactor”. Relevant preclinical and clinical studies were selected based on their contribution to vascularization strategies in scaffold-based bone regeneration, with the aim of illustrating the evolution and integration of these approaches. Results: Vascularized flaps provide an established vascular network and a biologically active microenvironment that promote scaffold integration and tissue regeneration. Periosteal flaps demonstrate strong osteogenic potential, whereas muscle and omental flaps primarily act as vascular carriers and adaptable regenerative environments. AV loop-based strategies enable intrinsic axial vascularization, ensuring rapid and homogeneous perfusion of large constructs. Hybrid approaches, including regenerative matching axial vascularization (RMAV), integrate vascularized tissues with advanced biomaterials and show promising translational outcomes. Conclusions: Vascularization-driven strategies represent a paradigm shift in bone tissue engineering, moving from passive scaffold implantation to actively engineered, vascularized constructs. The integration of microsurgical techniques with advanced biomaterials offers significant potential for the development of personalized and clinically applicable bone regeneration strategies. Full article
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26 pages, 4408 KB  
Review
Minimally Invasive Bone Regeneration in Implant Dentistry: From Biological Principles to Indication-Driven Clinical Decision-Making—A Narrative Review
by Paweł Porczyk and Bartłomiej Górski
J. Clin. Med. 2026, 15(11), 4208; https://doi.org/10.3390/jcm15114208 - 29 May 2026
Viewed by 929
Abstract
Background/Objectives: Contemporary implant dentistry is increasingly oriented toward minimally invasive regenerative strategies designed to reduce surgical morbidity while preserving or improving clinical outcomes. Conventional bone augmentation procedures remain effective and biologically well established, but they may be associated with greater patient burden, [...] Read more.
Background/Objectives: Contemporary implant dentistry is increasingly oriented toward minimally invasive regenerative strategies designed to reduce surgical morbidity while preserving or improving clinical outcomes. Conventional bone augmentation procedures remain effective and biologically well established, but they may be associated with greater patient burden, increased risk of complications, and higher technical demands in selected clinical scenarios. This narrative review critically examines minimally invasive bone regeneration approaches in implant dentistry, with particular focus on the Bone Core Technique, the Sub-Periosteal Peri-implant Augmented Layer (SPAL) technique, and Immediate Dentoalveolar Restoration (IDR), emphasizing their biological rationale, clinical indications, surgical workflows, limitations, and reported outcomes. Methods: A structured, non-systematic literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science to identify publications relevant to minimally invasive bone regeneration in implant dentistry. Priority was given to clinical studies, prospective cohorts, case series, technical descriptions, and biologically oriented conceptual papers addressing vascular preservation, flap limitation, donor-site morbidity, and peri-implant hard- and soft-tissue integration. Results: Available evidence suggests that minimally invasive regenerative protocols may offer favorable clinical and patient-centered outcomes only in carefully selected indications and when performed by experienced operators. The strength of support is uneven across techniques: the Bone Core Technique currently has the strongest dedicated prospective follow-up for localized peri-implant defects, SPAL is supported by limited retrospective and emerging histologic evidence, and IDR remains largely based on case reports, technique-driven descriptions, and broader immediate implant literature. Conclusions: Minimally invasive bone regeneration reflects a shift toward biologically guided and patient-centered treatment concepts in implant dentistry, but it should not be interpreted as a universal substitute for conventional augmentation. Its successful application depends on careful case selection, sound knowledge of wound healing and defect morphology, and advanced surgical and prosthetic expertise. Further research should prioritize standardized outcome measures, longer follow-up, and comparative prospective studies. Full article
(This article belongs to the Special Issue Dental Implantology: Clinical Updates and Perspectives—2nd Edition)
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15 pages, 737 KB  
Systematic Review
Surgical Techniques and Materials Used in the Treatment of Complicated Otomastoiditis: A Systematic Review
by Maria Denisa Zica, Catalina Voiosu, Andreea Rusescu, Irina Ionita, Luana Maria Gherasie, Oana Ruxandra Alius, Alexandra Bizdu Branovici, Razvan Hainarosie and Viorel Zainea
J. Clin. Med. 2026, 15(10), 3911; https://doi.org/10.3390/jcm15103911 - 19 May 2026
Viewed by 597
Abstract
Background and Objectives: Complicated cholesteatomatous otomastoiditis includes a spectrum of inflammatory, suppurative, and destructive lesions affecting the temporal bone and surrounding critical structures, including the dura mater, labyrinth, facial nerve, sigmoid sinus, and skull base. The selection of appropriate surgical techniques and closure [...] Read more.
Background and Objectives: Complicated cholesteatomatous otomastoiditis includes a spectrum of inflammatory, suppurative, and destructive lesions affecting the temporal bone and surrounding critical structures, including the dura mater, labyrinth, facial nerve, sigmoid sinus, and skull base. The selection of appropriate surgical techniques and closure materials is decisive for long-term outcomes, functional preservation, and prevention of life-threatening complications. This systematic review and meta-analysis evaluates the evidence base for surgical approaches, intraoperative technologies, and autologous and synthetic closure materials used in the management of iatrogenic and disease-related fistulas in otomastoid surgery. Materials and Methods: A PRISMA 2020-compliant search was conducted across PubMed, Cochrane Library, Embase, and Scopus (2000–2024). The review was registered in PROSPERO (CRD420261370406). After the systematic screening process, 56 eligible studies involving 4218 patients were selected for inclusion. The primary outcome measures analysed were infection rates, fistula recurrence, preservation of function, and long-term integrity of the closure. Limitations include the predominance of observational studies and the absence of prospective registration prior to data extraction. Results: Autologous materials demonstrated consistently low infection rates (<10%) in contaminated operative fields and therefore remain the preferred first-line option for the reconstruction of small to moderate defects. In contrast, synthetic materials exhibited superior mechanical durability in large sterile defects, achieving closure integrity rates of 85–92% at two-year follow-up. Hybrid reconstructive constructs provided the most favourable overall outcomes, with pooled closure integrity reaching 91.6%, suggesting a synergistic advantage when combining biologic and synthetic components. Furthermore, the adjunctive use of combined microscopic–endoscopic surgical techniques was associated with a significant reduction in residual cholesteatoma rates (OR 0.56, 95% CI 0.38–0.82), supporting the growing role of endoscopic assistance in middle ear and mastoid surgery. When biologic closure strategies were appropriately selected according to defect characteristics and contamination status, functional preservation rates exceeded 90–95%, underscoring the importance of tailored reconstructive approaches. Conclusions: The durability of long-term outcomes is most strongly influenced by complete pathological clearance and by the strategic alignment of biomaterial properties with defect dimensions, contamination status, and surrounding anatomical structures. In response to these findings, an evidence-based algorithmic framework is proposed to facilitate rational intraoperative material selection. Full article
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