Search Results (292)

For decades, regeneration of alveolar bone defects has depended on traditional grafting options, such as autogenous/allogenic grafts or allografts. Recently, extracted teeth was introduced as an alternative graft source. Tooth autografts are being used and have gained significant attention due to their biocompatibility, osteoconductivity, osteoinductivity, and osteogenic properties. Furthermore, tooth allografts have potential to act as natural biocomposites for oral regeneration procedures and might be advantageous options in near future. Recent advances in tooth banking, including cryopreservation, can serve to maintain bioactivity and to improve the safety, viability, and regenerative potential of teeth. They might be revolutionary in oral surgery, offering a more sustainable solution to the growing demand for bone regeneration procedures. Nevertheless, challenges such as immunogenic responses, ethical issues, and regulatory constraints persist. Ongoing research and technological innovation continue to address these problems. To date, the success rates of tooth autografts are promising, and they are regarded as a reliable option in clinical practice, with predictable outcomes in alveolar ridge preservation, sinus augmentation, periodontal regeneration, guided bone regeneration (GBR), and endodontic surgery by providing natural scaffolds for cell integration and bone remodeling. However, the scientific literature on tooth allografts is lacking. Therefore, this review aimed to comprehensively evaluate the scientific literature for comparing the properties of tooth grafts with other grafting options, in terms of processing techniques, and various clinical applications, positioning them as versatile biocomposites for the future, bridging material science and regenerative dentistry. Furthermore, possible applications of allogenic tooth grafts and overcoming current limitations are also discussed. Full article

Background and Clinical Significance: Common Variable Immunodeficiency (CVID) is a prevalent manifestation of primary immunodeficiency disorder. The current mainstay of treatment is immunoglobulin replacement therapy; however, in patients with severe complications or refractory disease, hematopoietic stem cell transplant (HSCT) is indicated. Despite this, there has been little research regarding HSCT as a treatment for CVID, with few case reports demonstrating clinical benefit. Case presentation: We present a unique case of common variable immunodeficiency Type XII (CVID12) with rare NFKB mutation and its management. A 20-year-old female with autoimmune alopecia, eczema, and a congenital atrophic right kidney presented to the emergency department with a three-month history of intermittent fever, malaise, lymphadenopathy, mouth sores, diarrhea, and odynophagia, accompanied by a 5 lb. unintentional weight loss and night sweats. Previously, she received multiple steroid prescriptions for these symptoms, providing only temporary relief with each course. Lab findings revealed severe neutropenia and imaging demonstrated hepatosplenomegaly and lymphadenopathy. Flow cytometry revealed a slightly atypical CD8-positive T-cell population and bone marrow biopsy revealed variable cellular marrow with trilineage hematopoiesis. Genetic testing confirmed the diagnosis of Autosomal Dominant Common Variable Immunodeficiency Type XII with an NFKB1 mutation. Pre-transplant treatments included monthly IVIG, weekly rituximab, and daily filgrastim, all of which failed to improve her autoimmune neutropenia and hypogammaglobulinemia and failed to reduce her symptomatic burden. Given the patient’s young age and refractory autoimmune neutropenia, it was decided to manage them definitively with hematopoietic stem cell transplantation (HSCT). She ultimately underwent allogenic stem cell transplantation (haploidentical, donor was the mother) with 3.96 × 10⁸/kg TNC without immediate post-transplant complications. Conclusions: This article demonstrates a rare case of NFKB1-positive CVID that was successfully treated with HSCT and highlights the importance of considering transplant therapy in younger patients with clinically significant, refractory autoimmune cytopenia. Full article

Background: Sarcina ventriculi is a bacterium predominantly reported in the stomach and associated with emphysematous gastritis, delayed gastric emptying, gastroparesis, or gastric outlet obstruction. Its prevalence is increasing among patients with a history of organ transplants, immunosuppression, and graft-versus-host disease (GVHD). This bacterium can be detected on histology with characteristic tetrad packet morphology; however, confirmation requires PCR and molecular studies. The role of Sarcina ventriculi in human diseases is not fully understood and has unclear clinical significance. While certain studies point to a possible pathogenic role, others regard its detection as incidental with no clear clinical consequence. Case presentation: Herein, we report a case of a 39-year-old male patient with primary refractory cHL, stage IVb, who underwent an autologous bone marrow transplant (BMT) and an allogeneic stem cell infusion. His post-transplant course was complicated by chronic kidney disease (CKD), malnutrition, depression, myopathy, skin, and colon GVHD. He eventually developed sepsis, was admitted to the ICU and developed multiorgan failure and passed away. The patient developed diarrhea, and the gastrointestinal specialist was consulted and revealed ulcerated ileitis and colitis. Biopsies were taken to evaluate for CMV infection and GVHD. The terminal ileum biopsy mainly revealed ulceration with granulation tissue formation and abundant microorganisms arranged in distinctive tetrads, characteristic of Sarcina ventriculi. The colonic biopsies were consistent with GVHD grade II. Conclusions: The significance of Sarcina microorganisms and their mechanisms of injury remain poorly understood. The identification of Sarcina ventriculi in the terminal ileum, which is an unusual and previously unreported finding, adds a new perspective to our understanding of its pathogenic potential and anatomical distribution. While the patient’s clinical decline was influenced by multiple factors, including GVHD, recurrent sepsis, and multiorgan failure, the role of Sarcina ventriculi as a potential exacerbating factor remains unclear. Full article

Extracellular vesicles (EVs) derived from bacteria are emerging as potent bioactive carriers that affect host immunity. Deinococcus radiodurans, an extremophilic bacterium with strong antioxidant capacity, produces EVs enriched in deinoxanthin (DX), a carotenoid with a reactive oxygen species–scavenging activity. Here, we assessed the antioxidant activity of D. radiodurans-derived EVs (R1-EVs) in biochemical assays and their immunomodulatory effects on dendritic cells (DCs). R1-EVs exhibited significantly higher antioxidant activity than EVs from a DX-deficient mutant strain (ΔcrtI-EVs), consistent with DX enrichment. Bone marrow-derived DCs treated with R1-EVs in the presence of lipopolysaccharide displayed reduced expression of surface maturation markers and pro-inflammatory cytokines, while interleukin-10 (IL-10) production and antigen uptake were preserved, indicating a tolerogenic phenotype. This tolerogenic program led to decreased proliferation and cytokine production in allogeneic CD4⁺ and CD8⁺ T cells. Mechanistically, R1-EVs inhibited mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways, key regulators of the DC activation. Importantly, IL-10 neutralization reversed these effects, restoring DC and T cell activation. Notably, ΔcrtI-EVs showed weaker antioxidant and immunoregulatory activities. Together, our findings identify R1-EVs as dual-functions, DX- and IL-10-dependent nanoplatform that integrates antioxidant and tolerogenic properties, with potential applications in inflammatory and autoimmune disease control. Full article

Background/Objectives: Hematogones, B cell precursors, are considered a clock of bone marrow reconstitution after chemotherapy and hematopoietic stem cell transplantation (HSCT). Methods: In this retrospective observational monocentric study, we investigated the prognostic role of hematogone expansion after allogeneic HSCT and its association with clinical and molecular features. Results: Using a cut-off value of 0.1%, hematogones were detected in 60% of patients at the first re-evaluation after HSCT (median, 2.4%; range, 0.2–9.0%) and in 63% of subjects at the most recent evaluation (MRR) (median, 1.4%; range, 0.1–5.1%). In particular, prolonged hematogone expansion was associated with longer overall survival (p = 0.0043) and relapse-free survival (p = 0.0002). No associations were described between hematogone frequency and stem cell sources or acute or chronic graft versus host disease incidence. Conclusions: In conclusion, our results confirmed that hematogones mirrored bone marrow fitness and reconstitution ability; thus, they could be used as a prognostic marker of HSCT outcomes. Full article

Recent decades have been characterized by increasing numbers of bone tissue injuries and diseases resulting in the formation of bone defects. The number of such bone defects has also grown due to active surgical approaches implemented after surgical interventions for oncological, infectious, and dystrophic bone lesions. To repair such bone defects requires the use of bone tissue substitutes. Nowadays, constructs based on matrices of various compositions and structures, supplemented with the addition of biologically active components (including growth factors and cells), are the most promising approaches used in bone tissue engineering. The properties of the matrices are of the utmost importance in construct formation. This work presents the results of a comprehensive study of matrices of various natures intended for the formation of complex constructs for bone tissue engineering. Using a set of methods for studying the physical, mechanical, and biological characteristics, the total and associated porosity of the studied matrices, the structure, the mechanical parameters, and the level of cytotoxicity and cytocompatibility were determined. It was shown that all the studied materials were not cytotoxic (cytotoxicity rank of all matrices = 0–1). All matrices were porous, but samples of materials of biological origin had large pores ranging in size from 100 to 1000 μm, and pores of the hybrid polymer were sized from 0.1 to 100 μm. Total and open porosity ranged from 89% and 79% for the allogeneic matrix up to 67% and 48% for the hybrid polymer, respectively, while the σ values (compressive stress at break) of samples of all studied materials were close to each other. When human test culture MSCs interact with samples of these materials, it was shown that the cells adhere to the surface and structure of all materials and retain typical morphology, while also demonstrating the ability to proliferate and migrate along the surface and into the matrix structure, i.e., all materials are cytocompatible. Based on the data obtained, it can be assumed that all the studied matrices can be used for model biomedical studies and as a basis for constructs for bone tissue engineering. An adequate choice of research method at the earliest stages of the development of each material will ensure the most effective approaches for further work and subsequent use of this product. Full article

Successful non-union therapy consists of a combination of optimizing mechanical stability and activating biological factors. The conventional method for treating non-union is debridement and stabilization with metal hardware. The human allogeneic cortical bone screw (Shark Screw^®) merges human cortical bone properties with screw stability, addressing non-union surgery principles by integrating mechanical and biological aspects. The objective of this retrospective study was to compare the clinical and radiological outcomes of the conventional method with those of the new method using the Shark Screw^®. This retrospective, multicentre, level III study included 41 patients with non-unions in upper extremities, 11 treated with the conventional method (metal hardware ± graft), and 30 patients with the Shark Screw^® (±graft). Patient demographics, non-union location, autograft and/or allograft use, follow-up time, complications, union rate, time to union, and time to return to work were recorded. Follow-up was 18 months in the conventional group and 10 months in the Shark Screw^® group. The union rate was 72.7% in the conventional group and 96.7% in the Shark Screw^® group. Time to union was significantly shorter in the Shark Screw^® group. In the conventional group, the complication rate was 36%, and it was 3.4% in the Shark Screw^® group. Hardware removal in the conventional group was 64%, and it was 0% in the Shark Screw^® group. The Shark Screw^® presents a reliable option for treating non-unions in the shoulder, forearm, hand, and fingers. Full article

Background: The growing demand for effective methods of bone tissue regeneration highlights the relevance of studying modern bone substitutes and their applications in regenerative medicine. The aim of this work was to conduct a comprehensive analysis of the biological, mechanical, and clinical characteristics of various types of bone substitutes to determine their potential in regenerative medicine. Methods: The study was performed as a systematic literature review in accordance with PRISMA guidelines, analyzing 68 high-quality scientific sources from 2019 to May 2025, using the PubMed, Scopus, Web of Science, and Google Scholar databases. Results: It was established that autogenous grafts exhibit the highest osteogenic properties due to the presence of growth factors BMP-2, BMP-7, and concentrated growth factors; however, their use is limited by donor site morbidity in 20–30% of patients and the requirement to treat 6% of fractures complicated by non-union. Allogeneic and xenogeneic substitutes provide structural support for large defects but require intensive processing in accordance with European Directives 2004/23/EC and 2006/86/EC to minimize the risk of infection transmission. Synthetic substitutes based on calcium phosphate ceramics with pore sizes ranging from 23 to 210 micrometres demonstrate excellent biocompatibility and controlled degradation, with β-tricalcium phosphate exhibiting optimal characteristics for long-term applications compared to calcium sulphate. Conclusions: The findings of the study highlight the necessity of a personalized approach in selecting bone substitutes, considering the specific requirements of medical specialities, and support the development of hybrid biomaterials to combine structural strength with biological activity. Full article

Background: Donor lymphocyte infusion (DLI) is employed to enhance the graft-versus-leukemia (GvL) effect and improve remission rates following allogeneic hematopoietic cell transplantation (alloHCT). However, graft-versus-host disease (GvHD) remains a significant complication of both alloHCT and DLI. Regular exercise has been shown to reduce cancer risk, enhance treatment responses, and mitigate therapy-related toxicities. This study investigated the effects of voluntary wheel running on GvL and GvHD following DLI in a xenogeneic mouse model. Methods: Immunodeficient NSG-IL15 mice were challenged with a luciferase-expressing chronic myelogenous leukemia cell line (K562), and then they received DLI with peripheral blood mononuclear cells (PBMCs) from healthy volunteers (GvL model). Non-tumor bearing mice received DLI to model GvHD. Half of the mice in each group were then given free access to a running wheel. Tumor growth (bioluminescence), GvHD, and body weight were monitored biweekly for ~40 days. Results: In the GvHD model, exercise extended overall survival by 60% and reduced GvHD severity. In the GvL model, exercise significantly lowered tumor burden and extended tumor-free survival in both DLI and vehicle control groups by 44.5% and 37.5%, respectively, suggesting both immune-dependent and immune-independent mechanisms. RNA sequencing of bone marrow from saline-injected mice revealed that genes associated with mitochondrial function, protein synthesis, and metabolic processes were downregulated in tumors from exercised mice. Conclusions: In summary, voluntary wheel running improved DLI outcomes by enhancing GvL and reducing GvHD. These benefits may be mediated, in part, through exercise-induced metabolic reprogramming of leukemia cells. Full article

This scoping review aimed to systematically map the literature on digital workflows for the design and fabrication of customized bone grafts in oral and maxillofacial surgery. The review focused on the integration of cone-beam computed tomography (CBCT), computer-aided design (CAD), and computer-aided manufacturing (CAM) techniques for the production of personalized bone blocks. A systematic search of PubMed, Web of Science, and Ovid MEDLINE identified 151 records published between 2015 and 2025; after duplicate removal, screening, and full-text assessment, 16 articles were included. Six additional seminal studies published before 2015 were considered through manual search to provide historical background. The included studies consisted of case reports, case series, prospective clinical investigations, and preclinical experiments. Customization strategies involved synthetic hydroxyapatite scaffolds, CAD/CAM-milled allogeneic blocks, xenogeneic blocks, and digitally guided autogenous grafts. Four studies provided direct clinical documentation of customized CAD/CAM bone blocks, while the others offered complementary evidence on digital design, scaffold adaptation, or preclinical validation. Outcomes included graft adaptation, volumetric stability, implant survival, and limited histological analyses. Despite promising short-term results, no study has yet described the complete clinical workflow from CBCT acquisition to milling and implantation of a biological autologous or xenogeneic block in humans. This review underscores both the feasibility and the limitations of current approaches, highlighting the absence of fully validated digital-to-biological protocols as the main gap to be addressed in future research. Full article

Cannabinoid receptor 1 (CB1) has been implicated in multiple inflammatory diseases by regulating pro-inflammatory mediators or altering immune cell polarization. However, the expression and direct functional role of CB1 in T cells remain largely unexplored. Here, we demonstrate that primary murine T cells express CB1 and that its novel agonist, BI-5756, directly increases the frequencies of regulatory T cells (Tregs) in primary murine pan T cells after activation. In addition, BI-5756 exhibits an in vivo protective effect against graft-versus-host disease (GvHD), an allogeneic T cell-mediated inflammatory complication after allogeneic hematopoietic cell transplantation (allo-HCT), resulting in an improved overall survival with enhanced platelet recovery and reconstitution of bone marrow-derived B and T cells. BI-5756 also directly suppresses tumor cell growth and upregulates MHC I, MHC II, and CD80 on tumor cells, which may subsequently enhance T cell-mediated anti-tumor responses in mixed lymphocyte reaction with A20 cells. The ability of BI-5756 to increase Tregs was significantly abrogated by rimonabant, a potent and selective CB1 antagonist, suggesting that the immunomodulatory effect of BI-5756 is mediated via CB1. In summary, BI-5756, a potent CB1 agonist, increases Tregs while preserving anti-tumor responses in vitro and effectively reduces GvHD in vivo. Full article

Cranial bone defects caused by trauma present significant clinical challenges but also difficulties in their forensic analysis. The complexity of cranial anatomy, limited vascularization, and proximity to neural structures complicate natural bone regeneration, often requiring surgical intervention and the use of complex materials and techniques. This review aims to identify relevant data for forensic analysis regarding bone regeneration after trauma, with an emphasis on the materials used and their interpretation in medico-legal contexts. It moves beyond a simple clinical perspective, providing a detailed medico-legal analysis of cranial bone repair and regeneration after trauma. This review aims to give a comprehensive analysis of the forensic and medico-legal consequences associated with cranial reconstruction using autogenic, allogenic, xenogenic, and synthetic materials. It gives a pioneering focus regarding an understudied but critical aspect of forensic and legal medicine, both to postmortem and to clinical elements. By detailing the unique radiographic signatures and physical characteristics of various reconstruction materials, we provide the specialists with a go-to material for the interpretation of these materials in forensic contexts. Furthermore, we will provide a detailed analysis of medico-legal risks, mainly those associated with malpractice claims, focusing our attention on the process of informed consent but also the management and interpretation of surgery-related complications. Full article

Introduction: Acute Myeloid Leukemia (AML) is a hematologic malignancy characterized by the clonal expansion of myeloid progenitors. While it primarily affects the bone marrow, extramedullary relapse occurs in 3–5% of cases, and it is linked to poor prognosis. Central nervous system (CNS) involvement presents diagnostic challenges due to nonspecific symptoms. CNS manifestations include leptomeningeal dissemination, nerve infiltration, parenchymal lesions, and myeloid sarcoma, occurring at any disease stage and frequently asymptomatic. Methods: A 62-year-old man with a recent history of AML in remission presented with diplopia and aching paresthesias in the left periorbital region spreading to the left frontal area. The diagnostic workup included neurological and hematological evaluation, lumbar puncture, brain CT, brain magnetic resonance imaging (MRI) with contrast, and dermatological evaluation with skin biopsy due to the appearance of nodular skin lesions on the abdomen and thorax. Results: Neurological evaluation showed hypoesthesia in the left mandibular region, consistent with left trigeminal nerve involvement, extending to the periorbital and frontal areas, and impaired adduction of the left eye with divergent strabismus in the primary position due to left oculomotor nerve palsy. Brain MRI showed an equivocal thickening of the left oculomotor nerve without enhancement. Cerebrospinal fluid (CSF) analysis initially showed elevated protein (47 mg/dL) with negative cytology; a repeat lumbar puncture one week later detected leukemic cells. Skin biopsy revealed cutaneous AML localization. A diagnosis of AML relapse with CNS and cutaneous localization was made. Salvage therapy with FLAG-IDA-VEN (fludarabine, cytarabine, idarubicin, venetoclax) and intrathecal methotrexate, cytarabine, and dexamethasone was started. Subsequent lumbar punctures were negative for leukemic cells. Due to high-risk status and extramedullary disease, the patient underwent allogeneic hematopoietic stem cell transplantation. Post-transplant aplasia was complicated by septic shock; the patient succumbed to an invasive fungal infection. Conclusions: This case illustrates the diagnostic complexity and poor prognosis of extramedullary AML relapse involving the CNS. Early recognition of neurological signs, including cranial nerve dysfunction, is crucial for timely diagnosis and management. Although initial investigations were negative, further analyses—including repeated CSF examinations and skin biopsy—led to the identification of leukemic involvement. Although neuroleukemiosis cannot be confirmed without nerve biopsy, the combination of clinical presentation, neuroimaging, and CSF data strongly supports the diagnosis of extramedullary relapse of AML. Multidisciplinary evaluation remains essential for detecting extramedullary relapse. Despite treatment achieving CSF clearance, the prognosis remains unfavorable, underscoring the need for vigilant clinical suspicion in hematologic patients presenting with neurological symptoms. Full article

Background: The impact of donor graft cell composition on post-HCT outcomes in AML remains controversial. Furthermore, it is unknown whether this interacts with pre-HCT MRD status. We evaluated the impact of CD34+ and CD3+ cell doses on outcomes of myeloablative conditioning (MAC) HCT in patients with myelodysplastic neoplasm (MDS)/AML or AML with and without detectable MRD in pre-HCT bone marrow specimens. Methods: We utilized an electronic database to identify all adults ≥18 years with MDS/AML or AML who underwent MAC and received 10/10 HLA-matched sibling or unrelated donor mobilized PBSC allografts in first morphologic remission between 2006 and 2023 at the University of Washington/Fred Hutchinson Cancer Center. Results: Among 385 adults, we found a progressive decrease in relapse incidence and improved survival with increasing CD34+ doses up to a threshold of 5.61 × 10⁶/kg, above which the relapse risk no longer decreased. After multivariable adjustment, a low CD34+ dose was associated with increased risk of relapse as well as lower overall and relapse-free survival. Similar results were obtained for patients with and without pre-HCT MRD. Higher CD3+ doses were linearly associated with an increased incidence of moderate–severe chronic GVHD. Conclusions: Our data identify a non-linear relationship between CD34+ cell dose and relapse risk in AML patients undergoing myeloablative allogeneic HCT, with no apparent added benefit beyond a CD34+ dose threshold. Our findings suggest that donor graft composition impacts outcomes in adults with AML undergoing allogeneic HCT after MAC, independent of pre-HCT MRD status; however, additional studies are needed for other donor cell scenarios. Full article

Alveolar bone loss due to trauma, extraction, or periodontal disease often requires bone grafting prior to implant placement. Although human allograft bone is widely used as an alternative to autograft, it has limited osteoinductive potential and a prolonged healing time. Mesenchymal stem cell–conditioned media (MSC-CM), rich in paracrine factors, has emerged as a promising adjunct to enhance bone regeneration. This study evaluated the regenerative effect of MSC-CM combined with human allograft bone in a rabbit calvarial defect model. Bilateral 8 mm defects were created in eight rabbits. Each animal received a human allograft alone (HB group) on one side and an allograft mixed with MSC-CM (HB+GF group) on the other. Histological and histomorphometric analyses were performed at 2 and 8 weeks postoperatively. Both groups showed new bone formation, but the HB+GF group demonstrated significantly greater bone regeneration at both time points (p < 0.05). New bone extended into the defect center in the HB+GF group. Additionally, greater graft resorption and marrow formation were observed in this group at 8 weeks. These findings suggest that MSC-CM enhances the osteogenic performance of human allograft bone and may serve as a biologically active adjunct for bone regeneration. Full article