Frank A. Schildberg

• Prof. Dr. rer. nat.
• Professor at University of Bonn

Osteoclasts (OCs) are important therapeutic targets in the treatment of osteoporosis. The aim of this study was to explore a novel therapeutic approach for osteoporosis using Arcyriaflavin A (ArcyA), a natural compound derived from the marine invertebrate Eudistoma sp. We systematically evaluated the effects of ArcyA on OC differentiation and funct...

Bacterial antibiotic resistance is an important challenge that the healthcare system is continually battling and a major problem in the treatment of musculoskeletal infections such as periprosthetic joint infections. Current methods to identify infectious microbes and define susceptibility to antibiotics require two to ten days from isolation to th...

Zusammenfassung Biofilmbildende Bakterien stellen im klinischen Alltag eine große Herausforderung dar. Dies gilt insbesondere für den bakteriellen Befall von Prothesen oder Osteosynthesematerial in der Orthopädie und Unfallchirurgie. Die Therapie mit Bakteriophagen bildet hierfür in der Zukunft, neben chirurgischem Débridement und Antibiotikagabe,...

Inflammation models with the proinflammatory cytokine interleukin-1β (IL-1β) are widely used in the in vitro investigation of new therapeutic approaches for osteoarthritis (OA). The aim of this study was to systematically analyze the influence of IL-1β in a 3D chondral pellet culture model. Bovine articular chondrocytes were cultured to passage 3 a...

Background Evidence states that persons with hemophilia are frequently affected by low bone mineral density (BMD). Data assessing the relationship between severity of hemophilia and occurrence of osteoporosis are lacking. Objectives This prospective cohort study aimed to assess the impact of hemophilia severity on BMD and to investigate trabecular...

Fragestellung: In den vergangenen Jahren hat uns das Thema Antibiotikaresistenz, Protheseninfektionen und steigende Revisionsraten Kopfschmerzen bereitet. Die Bakteriophagen stellen einen Hoffnungsschimmer in der Welt der Revisionsendoprothetik dar. Wir stellen uns deshalb in diesem Review die Frage: wie ist der aktuelle Kenntnisstand über die in v...

Tumor necrosis factor alpha (TNFα), as a key pro-inflammatory cytokine, plays a central role in joint diseases. In recent years, numerous models of TNFα-induced cartilage inflammation have been developed. However, due to the significant differences between these models and the lack of consensus in their construction, it becomes difficult to compare...

Inflammation models are widely used in the in vitro investigation of new therapeutic approaches for osteoarthritis. TNFα (tumor necrosis factor alpha) plays an important role in the inflammatory process. Current inflammation models lack uniformity and make comparisons difficult. Therefore, this study aimed to systematically investigate whether the...

Background: There is limited research on body composition in persons with hemophilia (PwH). The literature describes an increased body fat distribution and decreased lean mass in PwH compared to healthy controls using bioimpedance analysis. Using dual x-ray absorptiometry (DXA), which is known to be the most accurate method, this investigation aims...

Light sheet fluorescence microscopy (LSFM) is a transformative imaging method that enables the visualization of non-dissected specimen in real-time 3D. Optical clearing of tissues is essential for LSFM, typically employing toxic solvents. Here, we test the applicability of a non-hazardous alternative, ethyl cinnamate (ECi). We comprehensively chara...

Considering the fact that Toxoplasma is a common parasite of humans and Toxoplasma bradyzoites can reside in skeletal muscle, T. gondii-mediated immune responses may modulate the progression and pathophysiology of another musculoskeletal disorder, osteoporosis. In the current study, we investigated the association of bone health and Toxoplasma gond...

Simple Summary Bone marrow (myelo-) fibrosis in myeloproliferative neoplasms is associated with poor prognosis and treatment failure emphasizing the importance of investigating novel treatment approaches outside the JAK pathway. This study investigates the role of neuropilin 2 (NRP2) in myelofibrosis and bone formation, identifies the type of strom...

Introduction Osteomyelitis (OMS) is a bone infection causing bone pain and severe complications. A balanced immune response is critical to eradicate infection without harming the host, yet pathogens manipulate immunity to establish a chronic infection. Understanding OMS-driven inflammation is essential for disease management, but comprehensive data...

The biological reconstruction of periprosthetic acetabular defects is essential for the success of revision total hip arthroplasty. However, a standardized in vivo defect model with good analogy to the human situation is still lacking, which has significantly limited the research and development of this highly important clinical entity. A defined a...

The current gold standard to treat large cartilage defects is autologous chondrocyte transplantation (ACT). As a new surgical method of cartilage regeneration, minced cartilage implantation (MCI) is increasingly coming into focus. The aim of this study is to investigate the influence of chondrogenesis between isolated and cultured chondrocytes comp...

Objective The best time for cranioplasty (CP) after decompressive craniectomy (DC) is controversial, and there are no authoritative guidelines yet. Both complications as well as outcome may depend on the timing of CP. The aim of this single-center study was to evaluate the impact of late CP on procedural safety as well as on patient outcome. Metho...

Fragestellung: Der sogenannte chirurgische Rauch entsteht intraoperativ bei der elektrischen Verbrennung von Gewebe, z.B. bei der Elektrokoagulation oder zum Durchtrennen von Gewebe im Rahmen der Präparation. Er besteht aus potentiel gesundheitsschädlichen Bestandteilen, wie Feinstaub, polycyclische aromatische Kohlenwasserstoffe und flüchtige orga...

Background Aortic valve stenosis (AVS) is the most prevalent heart valve disease worldwide and mainly affects the elderly. In observational clinical studies, postmenopausal osteoporosis, which affects 30 % of all women, is associated with increased aortic valve calcification and stenosis. However, there are no pathomechanistic investigations that l...

Themenzuordnung: 21) Osteoporose, Osteologie und seltene Erkrankungen Fragestellung: Die Prävalenz von Osteoporose bei Männern liegt in Europa bei 9,7%. Ursächlich dafür ist häufig ein Testosteronmangel. Mehrere Studien weisen allerdings auf einen Zusammenhang von Osteoporose und der seltenen Erkrankung Hämophilie hin. Die Hämophilie ist durch den...

Biological augmentation of bony defects in weight-bearing areas of both the acetabulum and the femur remains challenging. The calcium-silicate-based ceramic Baghdadite is a very interesting material to be used in the field of revision total hip arthroplasty for the treatment of bony defects in weight-bearing and non-weight-bearing areas alike. The...

Introduction: Extracorporeal shock wave therapy is a non-invasive and effective option for treating various musculoskeletal disorders. Recent literature indicates that the parameters for extracorporeal shock wave therapy, such as the optimal intensity, treatment frequency, and localization, are yet to be determined. Studies reporting on the effects...

Background: Osteoarthritis is a degenerative joint disease that is becoming increasingly common as the population ages. Conservative treatment for hip or knee osteoarthritis has been limited to pain control. Intra-articular injections for targeted local treatment have been widely used in clinical practice for many years. Methods: This review is...

Monolateral pin-to-bar-clamp fixators are commonly used to stabilize acute extremity injuries. Certain rules regarding frame geometry have been established that affect construct stability. The influence of sagittal pin angulation on construct stiffness and strength has not been investigated. The purpose of this biomechanical study was to demonstrat...

Introduction Osteoarthritis (OA) affects a large percentage of the population worldwide. Current surgical and nonsurgical concepts for treating OA only result in symptom-modifying effects. However, there is no disease-modifying therapy available. Extracellular vesicles released by mesenchymal stem/stromal cells (MSC-EV) are promising agents to posi...

The biological enhancement of tissue regeneration and healing is an appealing perspective in orthopedics. We aimed to conduct a systematic review to describe the global distribution of studies investigating the use of adipose tissue derivates in orthopedics and to provide information on their quality and on the products available. The quality of th...

Osteomyelitis (OM) remains one of the most feared complications in bone surgery and trauma. Its diagnosis remains a major challenge due to lack of guidelines. The aim of this study was to prospectively analyze the value of the most common and available diagnostic tools and to establish an OM score to derive treatment recommendations. All patients w...

The subjective analysis of conventional radiography represents the principal method for bone diagnostics in endoprosthetics. Alternative objective quantitative methods are described but not commonly used. Therefore, semi-quantitative methods are tested using digital computation and artificial intelligence to standardize, simplify, and ultimately im...

Background: Surgical treatment of patients with osteoarthritis of the hip and persisting symptoms under conservative therapy has become increasingly important against the background of an aging population. Objectives: What are the physiological reactions in the interface between cementless implants and bone? Methods: The literature is reviewed...

Introduction Immune checkpoint inhibitors are used in the treatment of various cancers and have been extensively researched with regard to inflammatory and autoimmune diseases. However, this revolutionary therapeutic strategy often provokes critical auto-inflammatory adverse events, such as inflammatory reactions affecting the cardiovascular, gastr...

Motion capture analysis (MCA) has the advantage of providing a static and dynamic leg axis analysis without radiation. Nevertheless, there is a lack of evidence regarding the accuracy of this technique. To test whether mechanical femorotibial axis angle (MAA) measurement recorded with a non-invasive MCA system is equal to the gold standard static l...

Cartilage tissue has a very limited ability to regenerate. Symptomatic cartilage lesions are currently treated by various cartilage repair techniques. Multiple treatment techniques have been proposed in the last 30 years. Nevertheless, no single technique is accepted as a gold standard. Minced cartilage implantation is a newer technique that has ga...

A major complication of hemophilia A therapy is the development of alloantibodies (inhibitors) that neutralize intravenously administered coagulation factor VIII (FVIII). Immune tolerance induction therapy (ITI) by repetitive FVIII injection can eradicate inhibitors, and thereby reduce morbidity and treatment costs. However, ITI success is difficul...

Zusammenfassung Einführung Im Jahr 2020 erforderte die SARS-CoV-2-Pandemie eine Anpassung der Versorgungsstruktur in allen medizinischen Einrichtungen in Deutschland. Diese Studie analysierte die Auswirkungen der SARS-CoV-2-Pandemie im Fachbereich Orthopädie und Unfallchirurgie anhand der Jahresbilanz einer Universitätsklinik. Methoden Es wurde ein...

Immune checkpoint inhibitors have revolutionized immunotherapy against various cancers over the last decade. The use of checkpoint inhibitors results in remarkable re-activation of patients’ immune system, but is also associated with significant adverse events. In this review, we emphasize the importance of cell-type specificity in the context of i...

Knee joint osteoarthritis is a complex immunological and degenerative disease. Current treatment strategies fail to alter its progression. Mesenchymal stromal cell (MSC) therapy for osteoarthritis has been object of research for more than 30 years. The aim of MSC therapy is intended to be holistic, with regeneration of all affected knee joint struc...

Background and Aims Myeloid cells are key regulators of cirrhosis, a major cause of mortality worldwide. Because stromal cells can modulate the functionality of myeloid cells in vitro, targeting stromal-myeloid interactions has become an attractive potential therapeutic strategy. We aimed to investigate how human liver stromal cells impact myeloid...

Background Patients with severe haemophilia suffer from bleeding-related joint changes in which the ankle joint is most frequently affected. In the resulting gait changes, the forefoot is involved by reducing the foot pressure. However, it is unclear which changes in foot pressure are present in the individual's foot zones. Research question The a...

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences b...

Objective In the course of the corona pandemic, resource conservation and the protection of further infections have made it necessary to break new ground in the organisation of orthopaedic and trauma surgery consultations. One solution is consistent digitisation and the offer of video consultation hours. In this study, non-contact examination of pa...

The goal of this study is to evaluate the primary stability of a cementless augment-and-modular-cage system with and without the addition of cranial straps in a standardized in vitro setting. As the surrogate parameter for the evaluation of primary stability, the measurement of relative motion between the implant components themselves and the bone...

Mesenchymal stem cells (MSCs) are multipotent and considered to be of great potential for regenerative medicine. We could show recently (Breitbach, Kimura et al. 2018) that a subpopulation of MSCs as well as sinusoidal endothelial cells (sECs) in the bone marrow (BM) of CD73-EGFP reporter mice could be labeled in vivo. We took advantage of this mod...

Aseptic prosthetic loosening and periprosthetic joint infections (PJI) are among the most frequent complications after total knee/hip joint arthroplasty (TJA). Current research efforts focus on understanding the involvement of the immune system in these frequent complications. Different immune cell types have already been implicated in aseptic pros...

Simple Summary This up-to-date and in-depth review describes fibroblast-derived cells and their role within the tumor microenvironment for tumor progression. Moreover, targets for future antitumor therapies are summarized and potential aspects for future translational research are outlined. Furthermore, this review discusses the challenges and poss...

Background Video consultations could support patient care in hand surgery during social distancing in the COVID-19 era. According to the literature, images of hand and fingers can support telediagnosis in hand emergencies. We present this feasibility study on online video consultation in hand surgery. Methods A structured examination was designed t...

The incidence of musculoskeletal diseases is steadily increasing with aging of the population. In the past years, extracellular vesicles (EVs) have gained attention in musculoskeletal research. EVs have been associated with various musculoskeletal pathologies as well as suggested as treatment option. EVs play a pivotal role in communication between...

Tantalum (Ta) is gaining attention as a biomaterial in bone tissue engineering. Although the clinical advantage of Ta-based implants for primary and revision total joint replacement (TJA) has been well documented, few studies investigated the effect of wear products of Ta implants on peri-implant cells, and their potential contribution to aseptic i...

IntroductionDiagnosing a (low-grade) periprosthetic joint infection (PJI) after hip or knee arthroplasty remains a diagnostic challenge. The aim of this study was to evaluate the utility of using a novel multiplex protein microarray system for synovial biomarkers in determining PJI in patients undergoing revision knee or hip arthroplasty.Materials...

Osteoporosis is a disease characterized by low bone mass and an increased risk of fractures. Although several cellular players leading to osteoporosis have been identified, the role of mesenchymal stromal cells (MSC) is still not fully elaborated. The aim of this study was, therefore, to isolate and characterize MSCs from vertebral body of healthy...

Cartilage regeneration with cell-free matrices has developed from matrix-associated autologous cartilage cell transplantation (MACT) over ten years ago. Adjustments to the legal framework and higher hurdles for cell therapy have led to the procedures being established as an independent alternative to MACT. These procedures, which can be classified...

Background: Minimally invasive total knee arthroplasty (TKA) has been actively advertised by the orthopedic industry. The purpose of this network meta-analysis was to comprehensively compare the effectiveness of four minimally invasive surgery (MIS) approaches and the medial parapatellar (MPP) approach to improve the American Knee Society Score (KS...

Accurate diagnosis of periprosthetic joint infections (PJI) is one of the most widely researched areas in modern orthopedic endoprosthesis. However, our understanding of the immunological basis of this severe complication is still limited. In this study, we developed a flow cytometric approach to precisely characterize the immune cell composition i...

Over the last decades, joint arthroplasty has become a successful treatment for joint disease. Nowadays, with a growing demand and increasingly younger and active patients accepting these approaches, orthopedic surgeons are seeking implants with improved mechanical behavior and longer life span. However, aseptic loosening as a result of wear debris...

Infection is one of the most challenging complications after total joint arthroplasties affecting up to 30,000 patients in the US per year. This study investigates the psycho-social burden induced by the two-stage intervention in infected hip or knee replacements. All patients were treated with a two-stage exchange and were assessed at three differ...

Cartilage regeneration with cell-free matrices has developed from matrix-associated autologous cartilage cell transplantation (MACT) over ten years ago. Adjustments to the legal framework and higher hurdles for cell therapy have led to the procedures being established as an independent alternative to MACT. These procedures, which can be classified...

As the percentage of overweight individuals in the population rises, diseases associated with excess weight resulting from poor nutrition are becoming more and more widespread. So far, the influence of weight or nutrition on bone health has shown conflicting results. In the literature, the existing studies disagree about the effect of diet on bones...

Mesenchymal stromal cells (MSC) harvested in different tissues from the same donor exhibit different phenotypes. Each phenotype is not only characterized by a certain pattern of cell surface markers, but also different cellular functionalities. Only recently were different harvesting and processing techniques found to contribute to this phenomenon...

Aseptic loosening subsequent to periprosthetic osteolysis is the leading cause for the revision of arthroplasty failure. The biological response of macrophages to wear debris has been well established, however, the equilibrium of bone remodeling is not only dictated by osteoclastic bone resorption but also by osteoblast-mediated bone formation. Inc...

IntroductionThe treatment of severe acetabular bone loss remains a difficult challenge. No classification system is available that combines intuitive use, structured design and offers a therapeutic recommendation according to the current literature and modern state of the art treatment options. The goal of this study is to introduce an intuitive, r...

Periprosthetic joint infection (PJI) is a feared complication after arthroplasty. Our hypothesis was that PJI caused by difficult-to-treat (DTT) pathogens has a worse outcome compared with non-DTT PJI. Routine clinical data on 77 consecutive patients with confirmed PJI treated with two-stage exchange arthroplasty were placed in DTT and non-DTT PJI...

Background and Objectives: There are currently no data available regarding pediatric scoliosis surgery in Latvia. The aim of this article is to present treatment specific variables, investigate their interrelation, and identify predictors for the length of stay after surgical pediatric scoliosis correction. Materials and Methods: This retrospective...

Currently, there is an increasing focus on mesenchymal stromal cells (MSC) as therapeutic option in bone pathologies as well as in general regenerative medicine. Although human MSCs have been extensively characterized and standardized, ovine MSCs are poorly understood. This limitation hampers clinical progress, as sheep are an excellent large anima...

PD-1 as an immune checkpoint molecule down-regulates T cell activity during immune responses in order to prevent autoimmune tissue damage. In chronic infections or tumors, lasting antigen-exposure leads to permanent PD-1 expression that can limit immune-mediated clearance of pathogens or degenerated cells. Blocking PD-1 can enhance T cell function;...

Extracellular vesicles (EVs) comprise an as yet insufficiently investigated intercellular communication pathway in the field of revision total joint arthroplasty (RTJA). This study examined whether periprosthetic joint synovial fluid contains EVs, developed a protocol for their isolation and characterized them with respect to quantity, size, surfac...

Immunology, already a discipline in its own right, has become a major part of many different medical fields. However, its relationship to orthopedics and trauma surgery has unfortunately, and perhaps unjustly, been developing rather slowly. Discoveries in recent years have emphasized the immense breadth of communication and connection between both...

Background and objective: Musculature affected during spondylodesis surgery may benefit and recover faster if supported by spine orthosis postoperatively. Methods: This prospective study included 50 consecutive patients undergoing one- or two-level spondylodesis. The intervention group received a lumbar spine orthosis (n= 23), while the control...

Periprosthetic joint infection is among the most common and severe complications in total joint arthroplasty. Today, a combination of different methods is used for diagnosis because no single method with sufficient sensitivity and specificity is available. In this study, we explored the usability of single-molecule microscopy to characterize synovi...

: Microcirculatory integrity and proper function are the cornerstones to tissue nourishment and viability. In the clinical environment extended immobility, injuries, and inflammatory reactions demand local microcirculatory adaption to provide adequate supply. Assessment of endothelial adjustment capability and microcirculatory perfusion status, as...

Lymph node fibroblastic reticular cells (FRCs) respond to signals from activated T cells by releasing nitric oxide, which inhibits T cell proliferation and restricts the size of the expanding T cell pool. Whether interactions with FRCs also support the function or differentiation of activated CD8⁺ T cells is not known. Here we report that encounter...

The differentiation between aseptic loosening and periprosthetic joint infection is still one of the most challenging tasks of revision arthroplasty. Research on infection-associated cell communication has given rise to today's routine laboratory investigations. Within the field of arthroplasty synovial extracellular vesicles (EVs), com-prise a yet...

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell ty...

Background Patient expectations are an issue which is attracting increased interest in outcome research for knee surgery procedures. So far, research into patient expectations has mainly focused on the procedure and postoperative functional improvements. The purpose of this study was to identify patient expectations in the perioperative setting. Ma...

Background Variations in the temperature of body and skin are symptoms of many pathological changes. Although joint replacement surgery of hip and knee has been very successful in recent decades, periprosthetic infection is a growing problem and the number one reason for revision. While many studies have investigated changes in blood levels, invest...

Historically pediatric scoliosis represents a condition deeply rooted within the origins of orthopedic surgery. Today only a few subspecialized surgeons treat pediatric scoliosis patients. In severe cases surgery can hold progression of and correct pathologic spinal curvature. The goal of this article is to provide an overview of the current state...

Background: Several studies showed encouraging results after total disc replacement (TDR) in patients with cervical-brachial syndrome (CBS). Objective: The aim of this study was to supplement the existing documentation of results after total disc replacement and to underline the importance of the correct indication. Methods: The clinical and r...

Introduction Cartilage regeneration and restoration is a major topic in orthopedic research as cartilaginous degeneration and damage is associated with osteoarthritis and joint destruction. This systematic review aims to summarize current research strategies in cartilage regeneration research. Materials and methods A Pubmed search for models inves...

Background: Conventional radiography (CR) is the imaging method of choice in monitoring bone remodelling and other stability parameters after total hip arthroplasty (THA). Quantitative roentgen- or computed-tomography-based methods to determine bone density are prone to metal artifacts and often very costly, which is why they are not used as stand...

Chronic low-back pain (CLBP) has an increasing incidence and yields a tremendous health economic burden. There are different anatomic structures that may be responsible for CLBP, such as lumbar intervertebral discs, sacroiliac joints, nerve root dura, fascia, ligaments, and muscles. However, to a large extent, CLBP is associated with structural cha...

Purpose Patellar resurfacing (PR) in total knee arthroplasty (TKA) is still one of the major controversies in orthopaedic surgery today. The aim of the present retrospective case-control study was to identify predictors for secondary patellar resurfacing (SPR) after initial TKA to create a rationale for surgeons to decide which patients to resurfac...

Zusammenfassung Hintergrund Dreidimensionale (3-D) endoskopische Optiken können durch 2 Kameras die unterschiedliche Perspektive des rechten und linken Auges simulieren und somit die Illusion einer räumlichen Tiefe erzeugen. Im laparoskopischen Einsatz konnte eine optimierte Orientierung und ein exakteres Handling gegenüber 2-D-Optiken nachgewiesen...

Selenof (15-kDa selenoprotein; Sep15) is an endoplasmic reticulum (ER)-resident thioredoxin-like oxidoreductase that occurs in a complex with UDP-glucose:glycoprotein glucosyltransferase. We found that Selenof deficiency in mice leads to elevated levels of non-functional circulating plasma immunoglobulins and increased secretion of IgM during in vi...

The programmed death (PD)-1 coinhibitory receptor regulates the balance between T cell activation and tolerance. Although the PD-1 ligands, PD-L1 and PD-L2, are expressed on a variety of cell types, the cell type-specific functions of PD-1 ligands in inducing signals through PD-1 are unknown. In this study, we use PD-L1 conditional knockout mice to...