Bekir Karabucak’s research while affiliated with University of Pennsylvania and other places

Bacterial biofilms are pervasive and recalcitrant to current antimicrobials, causing numerous infections. Iron oxide-nanozymes, including an FDA-approved formulation (ferumoxytol, FMX), show potential against biofilm infections via catalytic activation of hydrogen peroxide (H2O2). However, clinical evidence on its efficacy and therapeutic mechanisms is lacking. Here, we investigate whether FMX-nanozymes can treat chronic biofilm infections and compare their bioactivity to gold-standard sodium hypochlorite (NaOCl), a potent but caustic disinfectant. Clinical performance was assessed in patients with apical periodontitis, an intractable endodontic infection affecting half of the global adult population. Data show robust antibiofilm activity by a single application of FMX with H2O2 achieving results comparable to NaOCl without adverse effects. FMX binds efficiently to bacterial pathogens Enterococcus faecalis and Fusobacterium nucleatum and remains catalytically active without being affected by dental tissues. This allows for effective eradication of endodontic biofilms via on-site free-radical generation without inducing cytotoxicity. Unexpectedly, FMX promotes growth of stem cells of apical papilla (SCAP), with transcriptomic analyses revealing upregulation of proliferation-associated pathways and downregulation of cell-cycle suppressor genes. Notably, FMX activates SCAP pluripotency and WNT/NOTCH signaling that induces its osteogenic capacity. Together, we show FMX nanozymes are clinically effective against severe chronic biofilm infection with pathogen targeting and unique stem cell-stimulatory properties, offering a regenerative approach to antimicrobial therapy.

Bacterial infections in irregular and branched confinements pose significant therapeutic challenges. Despite their high antimicrobial efficacy, enzyme‐mimicking nanoparticles (nanozymes) face difficulties in achieving localized catalysis at distant infection sites within confined spaces. Incorporating nanozymes into microrobots enables the delivery of catalytic agents to hard‐to‐reach areas, but poor nanoparticle dispersibility and distribution during fabrication hinder their catalytic performance. To address these challenges, a nanozyme‐shelled microrobotic platform is introduced using magnetic microcapsules with collective and adaptive mobility for automated navigation and localized catalysis within complex confinements. Using double emulsions produced from microfluidics as templates, iron oxide and silica nanoparticles are assembled into 100‐µm microcapsules, which self‐organize into multi‐unit, millimeter‐size assemblies under rotating magnetic fields. These microcapsules exhibit high peroxidase‐like activity, efficiently catalyzing hydrogen peroxide to generate reactive oxygen species (ROS). Notably, microcapsule assemblies display remarkable collective navigation within arched and branched confinements, reaching the targeted apical regions of the tooth canal with high accuracy. Furthermore, these nanozyme‐shelled microrobots perform rapid catalysis in situ and effectively kill biofilms on contact via ROS generation, enabling localized antibiofilm action. This study demonstrates a facile method of integrating nanozymes onto a versatile microrobotic platform to address current needs for targeted therapeutic catalysis in complex and confined microenvironments.

Microorganisms are the primary aetiological factor of apical periodontitis. The goal of endodontic treatment is to prevent and eliminate the infection by removing the microorganisms. However, microbial biofilms and the complex root canal anatomy impair the disinfection process. Effective and precise endodontic therapy could potentially be achieved using advanced multifunctional technologies that have the ability to access hard‐to‐reach surfaces and perform simultaneous biofilm killing, removal, and detection of microorganisms. Advances in microrobotics are providing novel therapeutic and diagnostic opportunities with high precision and efficacy to address current biofilm‐related challenges in biomedicine. Concurrently, multifunctional magnetic microrobots have been developed to overcome the disinfection challenges of current approaches to disrupt, kill, and retrieve biofilms with the goal of enhancing the efficacy and precision of endodontic therapy. This article reviews the recent advances of microrobotics in healthcare and particularly advances to overcome disinfection challenges in endodontics, and provides perspectives for future research in the field.

Aim: To evaluate two- and three-dimensionally the effect of resorbable collagen-based bone-filling material on periapical healing of endodontic lesions with four-wall defects following endodontic microsurgery (EMS). Methodology: This parallel, randomized controlled superiority clinical trial involved 86 lesions with the strictly endodontic origin and four-wall defect morphology. EMS procedures were performed by calibrated postgraduate residents. Before flap closure, osteotomies were randomized to the control or treatment group. In the control group, the flap was repositioned with no material added. In the treatment group, a collagen-based bone-filling augmentation material was placed into the osteotomy. Clinical and radiographic examinations were completed after 12 months. Periapical healing was evaluated by blinded evaluators using periapical (PA) radiographs according to Molven's criteria and cone beam computed tomography (CBCT) scans according to PENN's 3D criteria. Cortical plate healing was scored according to the RAC/B index. The data were analysed using Fisher's exact test, Logistic regression models and Chi-squared test. The significance level was predetermined at p < .05. Results: Sixty-six cases were evaluated at the 12-month follow-up, with 30 and 36 cases in the control and treatment groups, respectively. Only the asymptomatic cases (control = 26, treatment = 32) were included in the radiographic evaluation. Twenty-three cases (88.5%) in the control and 28 (87.5%) cases in the treatment group demonstrated complete healing on PA radiographs (p = 1.000). On CBCT, 10 (38.4%) and 21 (65.6%) cases had completely healed in the control and treatment groups, respectively (p = .095). The re-establishment of the buccal cortical plate was detected in 12 (46.2%) and 22 (68.8%) cases in the control and treatment groups, respectively (p = .243). Conclusion: Within the limitations of the present study, the use of collagen-based bone-filling material had no statistically significant effect on the periapical healing of endodontic lesions with four-wall defect following EMS at the 12-month follow-up when evaluated by PA radiographs or CBCT scans. However, the observed higher percentage of a re-established cortical plate in the treatment group could suggest a clinical benefit that is of interest after surgical endodontic treatment.

Introduction: Currently, there are no studies evaluating the impact of 3D printed models on endodontic surgical treatment planning. The aims of this study were: 1) to determine if 3D models could influence treatment planning; and 2) to assess the effect of 3D supported planning on operator confidence. Materials: Endodontic practitioners (n=25) were asked to analyze a pre-selected CBCT scan of an endodontic surgical case and answer a questionnaire that elucidated their surgical approach. After 30 days, the same participants were asked to analyze the same CBCT scan. Additionally, participants were asked to study and to perform a mock osteotomy on a 3D printed model. The participants responded to the same questionnaire along with a new set of questions. Responses were statistically analyzed using Chi square test followed by either logistic or ordered regression analysis. Adjustment for multiple comparison analysis was done using a Bonferroni correction. Statistical significance was set at ≤0.005. Results: The availability of both the 3D printed model and the CBCT scan resulted in statistically significant differences in the participants' responses to their ability to detect bone landmarks, predict the location of osteotomy, and to determine the following: size of osteotomy, angle of instrumentation, involvement of critical structures in flap reflection and involvement of vital structures during curettage. In addition, the participants' confidence in performing surgery was found to be significantly higher. Conclusions: The availability of 3D printed models did not alter the participants' surgical approach but it significantly improved their confidence for endodontic microsurgery.

Backgroud/purpose The prevalence of carious lesions and traumatic injury in individuals between ages 6 and 12 is high. This study aimed to characterize pediatric patients aged 6–12 treated in the endodontic clinic and investigate the prevalence and patterns of their provided endodontic treatments. Materials and methods Clinical and radiographic records of patients (ages 6–12) referred to the postgraduate Endodontics clinic from June 2017 to June 2020 were reviewed. Demographics, pre-and post-operative conditions, type of endodontic treatment, and behavioral management were collected. Results A total of 6350 teeth from 6089 patients were treated in this period, and 425 teeth (6.7%) from 405 patients were included. Ages 9–11 were the most commonly treated age group. Significantly more lower molars (41.9%) and upper anterior teeth (36.7%) were treated (P < 0.05). The majority of teeth were diagnosed with pulp necrosis (39.5%), and the most common periapical diagnosis was normal apical tissues (39.8%), then symptomatic apical periodontitis (38.8%). The most common etiological factor was caries (63.5%). Two hundred six teeth (48.5%) were treated with root canal therapy, 161 teeth (37.9%) with vital pulp therapy, 46 teeth (10.8%) with apexification or regenerative endodontic procedure, 12 teeth (2.8%) with non-surgical retreatment. A statistically high number of patients (87.8%) tolerated the endodontic procedures without any sedation (P < 0.0001). Conclusion Pediatric patients aged 6–12 compose around 7% of the population treated at the postgraduate Endodontics clinic, reflecting the high demand for endodontic treatment in a pediatric mixed dentition population.