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Background: The search for an ideal bone substitute in reconstructive surgery has led to the exploration of various materials, with hydroxyapatite (HaP) emerging as a promising candidate due to its biocompatibility, osteoconductive properties, and structural similarity to human bone. Despite its potential, there is a paucity of data on the long-term safety and efficacy of HaP in facial skeletal reconstruction and augmentation., Methods: We conducted a systematic review following PRISMA 2020 guidelines, searching PubMed/MEDLINE, Google Scholar, CENTRAL, and Web of Science databases for studies on hydroxyapatite facial implants in reconstruction and augmentation., Results: Our search yielded 12 studies that met our inclusion criteria, encompassing 74 patients treated with HaP implants for various indications including facial fractures/defects, aesthetic facial balancing, and after tumor resection. The studies reported on outcomes such as implant integration, complications, aesthetic results, and patient satisfaction, with a general trend indicating positive outcomes for the use of HaP in facial reconstruction., Conclusion: Hydroxyapatite appears to be a viable and effective material for facial skeletal reconstruction and augmentation, offering benefits in terms of biocompatibility, osteoconductivity, and patient outcomes. However, limitations such as low mechanical strength and the need for further research on long-term safety and efficacy were identified. This review underscores the potential of HaP in craniofacial surgery while highlighting areas for future investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Kauke-Navarro, Knoedler, Knoedler and Safi.)

The proper closure of the access cavity between appointments during endodontic treatment is paramount and relies on temporary fillings. This systematic review evaluates the effectiveness of zinc oxide-based materials and glass-ionomer cement (GIC) as temporary coronal sealers after root canal treatment in extracted human teeth. Three databases were searched to identify randomized clinical trials that examined the sealing properties of various temporary sealing materials using dyes or stains as indicators. A total of seven in vitro studies that fulfilled the eligibility criteria were critically analyzed. These indicated significant variations in the relative sealing ability of the coronal breach of endodontically treated teeth, either by zinc oxide or GIC-based materials. While GIC-based material (e.g., Fuji IX and Fuji II) exhibited superior sealing of single-rooted teeth, zinc oxide-based material (e.g., Cavit, Coltosol, Caviton) also showed promising attributes. Resin-modified GIC formulations displayed enhanced physical properties, yet challenges related to adhesive failure and shrinkage during polymerization were observed. Zinc oxide-based materials have demonstrated superior coronal sealing effectiveness over certain GIC in controlled settings. Their premixed nature ensures consistent application and hygroscopic properties improve cavity sealing. However, the focus on dye penetration tests for microleakage in vitro may not fully represent the risk of bacterial infiltration. Thus, in vivo studies are crucial for validating these findings in clinical contexts., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Malignancies represent a persisting worldwide health burden. Tumor treatment is commonly based on surgical and/or non-surgical therapies. In the recent decade, novel non-surgical treatment strategies involving monoclonal antibodies (mAB) and immune checkpoint inhibitors (ICI) have been successfully incorporated into standard treatment algorithms. Such emerging therapy concepts have demonstrated improved complete remission rates and prolonged progression-free survival compared to conventional chemotherapies. However, the in-toto surgical tumor resection followed by reconstructive surgery oftentimes remains the only curative therapy. Breast cancer (BC), skin cancer (SC), head and neck cancer (HNC), and sarcoma amongst other cancer entities commonly require reconstructive surgery to restore form, aesthetics, and functionality. Understanding the basic principles, strengths, and limitations of mAB and ICI as (neo-) adjuvant therapies and treatment alternatives for resectable or unresectable tumors is paramount for optimized surgical therapy planning. Yet, there is a scarcity of studies that condense the current body of literature on mAB and ICI for BC, SC, HNC, and sarcoma. This knowledge gap may result in suboptimal treatment planning, ultimately impairing patient outcomes. Herein, we aim to summarize the current translational endeavors focusing on mAB and ICI. This line of research may serve as an evidence-based fundament to guide targeted therapy and optimize interdisciplinary anti-cancer strategies., Competing Interests: MP received speaker’s honoraria and travel funds from Amgen, Kite, and Takeda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Knoedler, Huelsboemer, Hollmann, Alfertshofer, Herfeld, Hosseini, Boroumand, Stoegner, Safi, Perl, Knoedler, Pomahac and Kauke-Navarro.)

Balancing the immune response after solid organ transplantation (SOT) and vascularized composite allotransplantation (VCA) remains an ongoing clinical challenge. While immunosuppressants can effectively reduce acute rejection rates following transplant surgery, some patients still experience recurrent acute rejection episodes, which in turn may progress to chronic rejection. Furthermore, these immunosuppressive regimens are associated with an increased risk of malignancies and metabolic disorders. Despite significant advancements in the field, these IS related side effects persist as clinical hurdles, emphasizing the need for innovative therapeutic strategies to improve transplant survival and longevity. Cellular therapy, a novel therapeutic approach, has emerged as a potential pathway to promote immune tolerance while minimizing systemic side-effects of standard IS regiments. Various cell types, including chimeric antigen receptor T cells (CAR-T), mesenchymal stromal cells (MSCs), regulatory myeloid cells (RMCs) and regulatory T cells (T regs ), offer unique immunomodulatory properties that may help achieve improved outcomes in transplant patients. This review aims to elucidate the role of cellular therapies, particularly MSCs, T cells, T regs , RMCs, macrophages, and dendritic cells in SOT and VCA. We explore the immunological features of each cell type, their capacity for immune regulation, and the prospective advantages and obstacles linked to their application in transplant patients. An in-depth outline of the current state of the technology may help SOT and VCA providers refine their perioperative treatment strategies while laying the foundation for further trials that investigate cellular therapeutics in transplantation surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer GM declared a shared affiliation, though no other collaboration, with one of the authors JI at the time of the review., (Copyright © 2024 Knoedler, Dean, Diatta, Thompson, Knoedler, Rhys, Sherwani, Ettl, Mayer, Falkner, Kilian, Panayi, Iske, Safi, Tullius, Haykal, Pomahac and Kauke-Navarro.)

Facial implantology, a crucial facet of plastic and reconstructive surgery, focuses on optimizing implant materials for facial augmentation and reconstruction. This manuscript explores the use of Polyetheretherketone (PEEK) implants in craniofacial surgery, highlighting the challenges and advancements in this field. While PEEK offers mechanical resilience, durability, and compatibility with imaging modalities, its biologically inert nature hinders integration with the host tissue, which may lead to complications. In this systematic review, our aim was to assess the current state of knowledge regarding the clinical evaluation of Polyetheretherketone (PEEK) implants in facial implantology, with a focus on craniofacial augmentation and reconstruction in human studies. Additionally, we explore and discuss surface and structural modifications that may enhance bioreactivity and reduce complications in PEEK implants. A systematic review identified 32 articles detailing the use of PEEK Patient-Specific Implants (PSIs) in 194 patients for both reconstructive and aesthetic purposes. Complications, including infections and implant failures, were reported in 18% of cases, suggesting the need for improved implant materials. The discussion delves into the limitations of PEEK, prompting the exploration of surface and structural modifications to enhance its bioreactivity. Strategies, such as hydroxyapatite coating, titanium coating, and porous structures show promise in improving osseointegration and reducing complications. However, the literature review did not reveal reports of coated or modified PEEK in facial reconstructive or aesthetic surgery. In conclusion, although PEEK implants have been successfully used in craniofacial reconstruction, their biological inertness poses challenges. Surface modifications, particularly hydroxyapatite coatings, provide opportunities to promote osseointegration. Future research should focus on prospective long-term studies, especially in craniofacial surgery, to investigate the stability of uncoated PEEK implants and the potential benefits of surface modifications in clinical applications. Patient-specific PEEK implants hold promise for achieving durable craniofacial reconstruction and augmentation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kauke-Navarro, Knoedler, Knoedler, Deniz and Safi.)

Facial reconstruction and augmentation, integral in facial plastic surgery, address defects related to trauma, tumors infections, and congenital skeletal deficiencies. Aesthetic considerations, including age-related facial changes, involve volume loss and diminished projection, often associated with predictable changes in the facial skeleton. Autologous, allogeneic, and alloplastic implants are used to address these concerns. Autologous materials such as bone, cartilage, and fat, while longstanding options, have limitations, including unpredictability and resorption rates. Alloplastic materials, including metals, polymers, and ceramics, offer alternatives. Metals like titanium are biocompatible and used primarily in fracture fixation. Polymers, such as silicone and polyethylene, are widely used, with silicone presenting migration, bony resorption, and visibility issues. Polyethylene, particularly porous polyethylene (MedPor), was reported to have one of the lowest infection rates while it becomes incorporated into the host. Polyether-ether-ketone (PEEK) exhibits mechanical strength and compatibility with imaging modalities, with custom PEEK implants providing stable results. Acrylic materials, like poly-methylmethacrylate (PMMA), offer strength and is thus mostly used in the case of cranioplasty. Bioceramics, notably hydroxyapatite (HaP), offer osteoconductive and inductive properties, and HaP granules demonstrate stable volume retention in facial aesthetic augmentation. Combining HaP with other materials, such as PLA, may enhance mechanical stability. 3D bioprinting with HaP-based bioinks presents a promising avenue for customizable and biocompatible implants. In conclusion, various materials have been used for craniofacial augmentation, but none have definitively demonstrated superiority. Larger randomized controlled trials are essential to evaluate short- and long-term complications comprehensively, potentially revolutionizing facial balancing surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kauke-Navarro, Knoedler, Knoedler, Deniz, Stucki and Safi.)

Facial vascularized composite allotransplantation (FVCA) is an emerging field of reconstructive surgery that represents a dogmatic shift in the surgical treatment of patients with severe facial disfigurements. While conventional reconstructive strategies were previously considered the goldstandard for patients with devastating facial trauma, FVCA has demonstrated promising short- and long-term outcomes. Yet, there remain several obstacles that complicate the integration of FVCA procedures into the standard workflow for facial trauma patients. Artificial intelligence (AI) has been shown to provide targeted and resource-effective solutions for persisting clinical challenges in various specialties. However, there is a paucity of studies elucidating the combination of FVCA and AI to overcome such hurdles. Here, we delineate the application possibilities of AI in the field of FVCA and discuss the use of AI technology for FVCA outcome simulation, diagnosis and prediction of rejection episodes, and malignancy screening. This line of research may serve as a fundament for future studies linking these two revolutionary biotechnologies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Knoedler, Knoedler, Allam, Remy, Miragall, Safi, Alfertshofer, Pomahac and Kauke-Navarro.)

Artificial intelligence (AI) has emerged as a versatile health-technology tool revolutionizing medical services through the implementation of predictive, preventative, individualized, and participatory approaches. AI encompasses different computational concepts such as machine learning, deep learning techniques, and neural networks. AI also presents a broad platform for improving preoperative planning, intraoperative workflow, and postoperative patient outcomes in the field of oral and maxillofacial surgery (OMFS). The purpose of this review is to present a comprehensive summary of the existing scientific knowledge. The authors thoroughly reviewed English-language PubMed/MEDLINE and Embase papers from their establishment to 1 December 2022. The search terms were (1) "OMFS" OR "oral and maxillofacial" OR "oral and maxillofacial surgery" OR "oral surgery" AND (2) "AI" OR "artificial intelligence". The search format was tailored to each database's syntax. To find pertinent material, each retrieved article and systematic review's reference list was thoroughly examined. According to the literature, AI is already being used in certain areas of OMFS, such as radiographic image quality improvement, diagnosis of cysts and tumors, and localization of cephalometric landmarks. Through additional research, it may be possible to provide practitioners in numerous disciplines with additional assistance to enhance preoperative planning, intraoperative screening, and postoperative monitoring. Overall, AI carries promising potential to advance the field of OMFS and generate novel solution possibilities for persisting clinical challenges. Herein, this review provides a comprehensive summary of AI in OMFS and sheds light on future research efforts. Further, the advanced analysis of complex medical imaging data can support surgeons in preoperative assessments, virtual surgical simulations, and individualized treatment strategies. AI also assists surgeons during intraoperative decision-making by offering immediate feedback and guidance to enhance surgical accuracy and reduce complication rates, for instance by predicting the risk of bleeding.

Fibula free flaps (FFF) represent a working horse for different reconstructive scenarios in facial surgery. While FFF were initially established for mandible reconstruction, advancements in planning for microsurgical techniques have paved the way toward a broader spectrum of indications, including maxillary defects. Essential factors to improve patient outcomes following FFF include minimal donor site morbidity, adequate bone length, and dual blood supply. Yet, persisting clinical and translational challenges hamper the effectiveness of FFF. In the preoperative phase, virtual surgical planning and artificial intelligence tools carry untapped potential, while the intraoperative role of individualized surgical templates and bioprinted prostheses remains to be summarized. Further, the integration of novel flap monitoring technologies into postoperative patient management has been subject to translational and clinical research efforts. Overall, there is a paucity of studies condensing the body of knowledge on emerging technologies and techniques in FFF surgery. Herein, we aim to review current challenges and solution possibilities in FFF. This line of research may serve as a pocket guide on cutting-edge developments and facilitate future targeted research in FFF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Baecher, Hoch, Knoedler, Maheta, Kauke-Navarro, Safi, Alfertshofer and Knoedler.)

Oral squamous cell carcinoma (OSCC) is a complex disease with a high potential for lymph node metastasis and poor survival rates. Accurate nodal staging is crucial for prognostic assessment and treatment planning in OSCC. Recent research has suggested that nodal tumor volume (NTV) may be a more accurate indicator of nodal disease burden than traditional staging methods. However, the prognostic significance of NTV in OSCC remains unclear. This systematic review aims to evaluate the existing evidence on the relationship between NTV and prognosis in OSCC. A comprehensive search of electronic databases was conducted, and studies meeting inclusion criteria were critically appraised and synthesized. Our review identified 23 studies that investigated the prognostic significance of NTV in OSCC. The majority of studies reported that larger NTV was associated with poorer survival outcomes, although the strength of the association varied. The review also identified several areas for future research, including the standardization of NTV measurement and the integration of NTV into the broader landscape of OSCC management. In conclusion, our review suggests that NTV holds promise as a novel prognostic factor in OSCC, but more research is needed to fully elucidate its potential and inform clinical decision-making., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Bernasconi, Bilic, Kauke-Navarro and Safi.)

Supplemental Digital Content is available in the text., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: There is unmet need for non-invasive immunomonitoring to improve diagnosis and treatment of acute rejection in vascularized composite allotransplantation (VCA). Circulating matrix metalloproteinase 3 (MMP3) was described as a candidate non-invasive biomarker to predict treatment response to acute rejection in clinical VCA. However, larger validation studies are yet to be reported to allow for more definitive conclusions. Methods: We retrospectively measured MMP3 levels using ELISA in a total of 140 longitudinal serum samples from six internal and three external face transplant recipients, as well as three internal and seven external upper extremity transplant recipients. The control groups comprised serum samples from 36 kidney transplant recipients, 14 healthy controls, and 38 patients with autoimmune skin disease. A linear mixed model was used to study the effect of rejection state (pre-transplant, no-rejection, non-severe rejection (NSR), and severe rejection) on MMP3 levels. Results: In VCA, MMP3 levels increased significantly ( p < 0.001) between pre- and post-transplant no-rejection states. A further increase occurred during severe rejection ( p < 0.001), while there was no difference in MMP3 levels between non-severe and no-rejection episodes. A threshold of 5-fold increase from pre-transplant levels could discriminate severe from NSR with 76% sensitivity and 81% specificity (AUC = 0.79, 95% CI = 0.65-0.92, p < 0.001). In kidney transplantation, the MMP3 levels were significantly ( p < 0.001) elevated during antibody-mediated rejection but not during T-cell mediated rejection (TCMR) ( p = 0.547). MMP3 levels in healthy controls and autoimmune skin disease patients were comparable with either pre-transplant or no-rejection/NSR episodes of VCA patients. Conclusion: The results of this study suggest that serum MMP3 protein is a promising marker for stratifying patients according to severity of rejection, complementary to biopsy findings., (Copyright © 2019 Kollar, Uffing, Borges, Shubin, Aoyama, Dagot, Haug, Kauke, Safi, Talbot, Morelon, Dakpe, Pomahac and Riella.)