Denitsa Docheva

• Prof. Dr.
• Head of Department at University of Wuerzburg & Orthopaedic Hospital König-Ludwig-Haus

Tendon regeneration has been one of the most challenging issues in orthopedics. Despite various surgical techniques and rehabilitation methods, tendon tears or ruptures cannot wholly regenerate and gain the load-bearing capacity the tendon tissue had before the injury. The enhancement of tendon regeneration mostly requires grafting or an artificial...

Fluoroquinolones (FQs) are an important class of potent broad‐spectrum antibiotics. However, their general use is more and more limited by adverse side effects. While general mechanisms for the fluoroquinolone‐associated disability (FQAD) have been identified, the underlying molecular targets of toxicity remain elusive. In this study, focusing on t...

Proper connections between cartilaginous and muscular primordia through tendinous/ligamentous primordia are essential for musculoskeletal integration. Herein, we report a novel double-reporter mouse model for investigating this process via fluorescently visualising scleraxis (Scx) and SRY-box containing gene 9 (Sox9) expression. We generated ScxTom...

Fluoroquinolones (FQs) are an important class of potent broad‐spectrum antibiotics. However, their general use is more and more limited by adverse side effects. While general mechanisms for the fluoroquinolone‐associated disability (FQAD) have been identified, the underlying molecular targets of toxicity remain elusive. In this study, focusing on t...

The fluoroquinolone (FQ) class of antibiotics includes the world’s most prescribed antibiotics such as ciprofloxacin, levofloxacin, and ofloxacin that are known for their low bacterial resistance. This is despite their potential to trigger severe side effects, such as myopathy, hearing loss, tendinopathy, and tendon rupture. Thus, healthcare organi...

Backgroud Intervertebral disc degeneration (IDD) is one of the common degenerative diseases. Due to ethical constraints, it is difficult to obtain sufficient research on humans, so the use of an animal model of IDD is very important to clarify the pathogenesis and treatment mechanism of the disease. Methods In this study, thirty 2‐month‐old mice w...

Background: The aim of our study was to examine the combined effects of tranexamic acid (TXA) and vancomycin powder (VP) on chondrocytes in vitro. Despite the use of TXA and VP being linked to a reduced risk of extensive postoperative blood loss and periprosthetic joint infections (PJIs) in TKA, the possible cytotoxic side effects on periarticular...

Fluoroquinolones (FQs) are an important class of potent broad-spectrum antibiotics. However, their general use is more and more limited by adverse side effects. While general mechanisms for the fluoroquinolone-associated disability (FQAD) have been identified, the underlying molecular targets of toxicity remain elusive. In this study, focusing on t...

Fluoroquinolones (FQs) are an important class of potent broad-spectrum antibiotics. However, their general use is more and more limited by adverse side effects. While general mechanisms for the fluoroquinolone-associated disability (FQAD) have been identified, the underlying molecular targets of toxicity remain elusive. In this study, focusing on t...

Introduction: Circulating precursor cell populations of various lineages have been identified with putative functions in tissue regeneration, which may have potential for cell based individual regenerative strategies. We previously demonstrated the enrichment of an angiogenic precursor cell population from peripheral blood mononuclear cells by CYR6...

Background The health-care sector and particularly the surgical sector are major contributors to the exacerbation of the global climate crisis. Little is known about the carbon emissions caused by surgical procedures. Therefore, the aim of this study was to estimate the carbon footprint associated with common orthopaedic surgical procedures. Metho...

Irisin, an exercise-induced myokine, is known to be able to regulate bone metabolism. However, the underlying mechanisms regarding the effects of irisin on senile osteoporosis have not been fully elucidated. Here, we demonstrated that irisin can inhibit bone mass loss and bone microarchitecture alteration in senile osteoporosis mouse model. In addi...

Tendons and ligaments (T/L) are strong hierarchically organized structures uniting the musculoskeletal system. These tissues have a strictly arranged collagen type I-rich extracellular matrix (ECM) and T/L-lineage cells mainly positioned in parallel rows. After injury, T/L require a long time for rehabilitation with high failure risk and often unsa...

Fibrocartilaginous entheses consist of tendons, unmineralized and mineralized fibrocartilage, and subchondral bone, each exhibiting varying stiffness. Here we examined the functional role of sclerostin, expressed in mature mineralized fibrochondrocytes. Following rapid mineralization of unmineralized fibrocartilage and concurrent replacement of epi...

Articular cartilage is crucial for joint function but its avascularity limits intrinsic repair, leading to conditions like osteoarthritis (OA). Chondromodulin-I (Cnmd) has emerged as a key molecule in cartilage biology, with potential implications for OA therapy. Cnmd is primarily expressed in cartilage and plays an important role in chondrocyte pr...

Multiple myeloma involves early dissemination of malignant plasma cells across the bone marrow; however, the initial steps of dissemination remain unclear. Human bone marrow–derived mesenchymal stromal cells (hMSC) stimulate myeloma cell expansion (e.g., IL6) and simultaneously retain myeloma cells via chemokines (e.g., CXCL12) and adhesion factors...

Background In our current study, we investigated the impact of tranexamic acid (TXA) and vancomycin powder (VP) on osteogenic differentiated human bone-marrow derived mesenchymal stromal cells (hBMSCs) in vitro. Although topical application of TXA and VP is widely used to prevent post-operative blood loss and perioperative joint infection (PJI) in...

Worldwide, tendon disorders are one of the main causes of disability that decrease the quality of life of individuals and represent a substantial economic burden on society. Currently, the main therapies used for tendon injuries are not able to restore tendon functionality, and due to tendons' hypovascular and hypocellular nature, they present a re...

The most prevalent extracellular matrix (ECM) protein in the meniscus is collagen, which controls cell activity and aids in preserving the biological and structural integrity of the ECM. To create stable and high-precision 3D printed collagen scaffolds, ink formulations must possess good printability and cytocompatibility. This study aims to overla...

Fibrocartilaginous entheses consist of four graded tissue layers including tendon, the unmineralized and mineralized fibrocartilage, and subchondral bone with varying degrees of stiffness. Here we examined the functional role of sclerostin that is expressed in mature mineralized fibrochondrocytes. Following rapid mineralization of the unmineralized...

Tendons are mechanosensitive connective tissues responsible for the connection between muscles and bones by transmitting forces that allow the movement of the body, yet, with advancing age, tendons become more prone to degeneration followed by injuries. Tendon diseases are one of the main causes of incapacity worldwide, leading to changes in tendon...

In the present study, we investigated the dynamics of a femtosecond (fs) laser induced bio-printing with cell-free and cell-laden jets under the variation of laser pulse energy and focus depth, by using time-resolved imaging. By increasing the laser pulse energy or decreasing the focus depth thresholds for a first and second jet are exceeded and mo...

Meniscus tears have been treated using partial meniscectomy to relieve pain in patients, although this leads to the onset of early osteoarthritis (OA). Cell-based therapies can help preserve the meniscus, although the presence of inflammatory cytokines compromises clinical outcomes. Anti-inflammatory drugs (e.g. celecoxib), can help to reduce pain...

Partial meniscectomy patients have a greater likelihood for the development of early osteoarthritis (OA). To prevent the onset of early OA, patient-specific treatment algorithms need to be created that predict patient risk to early OA after meniscectomy. The aim of this work was to identify patient-specific risk factors in partial meniscectomy pati...

Self-assembling three-dimensional organoids that do not rely on an exogenous scaffold but maintain their native cell-to-cell and cell-to-matrix interactions represent a promising model in the field of tendon tissue engineering. We have identified dermal fibroblasts (DFs) as a potential cell type for generating functional tendon-like tissue. The glu...

Background and Objective: Translational large animal models are inevitable to transfer cartilage repair methods into clinical practice. Guidelines for these trials have been published by guiding agencies (FDA, ASTM, EMEA) including recommendations for study descriptors and study outcomes. However, practical adherence to these recommendations is not...

Cartilage resides under a low oxygen tension within articulating joints. The oxygen tension within cartilage of the knee joint has been measured to be between 2% and 5% oxygen. Although the literature has historically termed this level of oxygen as hypoxia, particularly when doing experiments in vitro in this range, this is actually the physiologic...

Since ancient times, reduction and internal fixation has been applied to restore skeletal integrity. Despite advances in the understanding of fracture healing, the risk of complication such as implant loosening or implant-related infection still depicts a challenging complication. Nowadays, a great deal of research is devoted to unreveal the impact...

Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiolog...

This study characterized laser-deposited CaTiO3 coats on several substrates by electron microscopy, X-ray diffraction, and Raman spectra. The hydrolytic stability of such coats exposed to ambient air and immersed into culture and osteogenic media has been respectively assessed by X-ray photoelectron spectra and energy dispersive X-ray analysis. It...

Introduction: In chronic bone infection, marginal bone resection avoids large and difficult to reconstruct bone defects. However, there is still a lack of knowledge on bone regeneration during chronic bone infection and bone healing capability after marginal bone resection. Therefore, the purpose of this study was to investigate the clinical and hi...

Clinically relevant in vitro models of human tissue's health and disease are urgently needed for a better understanding of biological mechanisms essential for the development of novel therapies. Herein, physiological (healthy) and pathological (disease) tendon states are bioengineered by coupling the biological signaling of platelet lysate componen...

Aims Bone regeneration during treatment of staphylococcal bone infection is challenging due to the ability of Staphylococcus aureus to invade and persist within osteoblasts. Here, we sought to determine whether the metabolic and extracellular organic matrix formation and mineralization ability of S. aureus-infected human osteoblasts can be restored...

The meniscus is composed of an avascular inner region and vascular outer region. The vascular region has been shown to contain a progenitor population with multilineage differentiation capacity. Strategies facilitating the isolation and propagation of these progenitors can be used to develop cell-based meniscal therapies. Differential adhesion to f...

Heterotopic ossification (HO) represents a common problem after tendon injury with no effective treatment yet being developed. Tenomodulin (Tnmd), the best-known mature marker for tendon lineage cells, has important effects in tendon tissue aging and function. We have reported that loss of Tnmd leads to inferior early tendon repair characterized by...

Femtosecond laser pulses have been successfully used for film-free single-cell bioprinting, enabling precise and efficient selection and positioning of individual mammalian cells from a complex cell mixture (based on morphology or fluorescence) onto a 2D target substrate or a 3D pre-processed scaffold. In order to evaluate the effects of higher pul...

Objective The underlying mechanisms and molecular factors influencing intervertebral disc (IVD) homeostasis and degeneration remain clinically relevant. Tenomodulin (Tnmd) and chondromodulin (Chm1) are antiangiogenic transmembrane glycoproteins, with cleavable C-terminus, expressed by IVD cells that are implicated in the onset of degenerative proce...

This article reviews synthetic approaches, properties and potential use of nano and micron sized forms of particles and coats of calcium titanate CaTiO3 and its composites. Our aim is to classify these forms according to the way of their fabrication and provide a brief outline of synthetic methods, properties and potential applications of these for...

Titanium is commonly and successfully used in dental and orthopedic implants. However, patients still have to face the risk of implant failure due to various reasons, such as implant loosening or infection. The risk of implant loosening can be countered by optimizing the osteointegration capacity of implant materials. Implant surface modifications...

Novel types of titanium oxidic surfaces were fabricated by a shifted Laser Surface Texturing of titanium in air, producing porous micro/nanostructured topography, and by a subsequent Nd:YAG laser-induced reactive deposition of Ti5Si3 titanium silicide in vacuum, coating this topography with scattered sub-micron particles of silicon monoxide. Both s...

Orthopaedic and trauma research is a gateway to better health and mobility, reflecting the ever-increasing and complex burden of musculoskeletal diseases and injuries in Germany, Europe and worldwide. Basic science in orthopaedics and traumatology addresses the complete organism down to the molecule among an entire life of musculoskeletal mobility....

A correction to this paper has been published: https://doi.org/10.1007/s00167-021-06622-8

The unexplored effect of chemical treatment of laser micro/nanostructured titanium surfaces deserves attention due to broadening our knowledge of surface enhancement of biomimetic synthesis of hydroxyapatite and osseointegration of titanium implants. In this study, NaOH–CaCl2-heat-water treatment of titanium is revisited and used to modify porous l...

Tissue engineering requires the precise positioning of mammalian cells and biomaterials on substrate surfaces or in preprocessed scaffolds. Although the development of 2D and 3D bioprinting technologies has made substantial progress in recent years, precise, cell‐friendly, easy to use, and fast technologies for selecting and positioning mammalian c...

PurposeThis article provides an update on the current therapeutic options for cell-based regenerative treatment of the knee with a critical review of the present literature including a future perspective on the use of regenerative cell-based approaches. Special emphasis has been given on the requirement of a whole joint approach with treatment of c...

An anisotropic magnetically-responsive collagen hydrogel loaded with iron oxide nanoparticles augments aligned cell row formation and tenogenic gene expression of tendon stem/progenitor cells.

The periodontal ligament (PDL) is exposed to different kinds of mechanical stresses such as bite force or orthodontic tooth movement. A simple and efficient model to study molecular responses to mechanical stress is the application of compressive force onto primary human periodontal ligament fibroblasts via glass disks. Yet, this model suffers from...

In Greek mythology, Achilles, the Greek hero, is almost invulnerable—except for his Achilles heel, whose injury resulted in his death[...]

The sol–gel derived porous bioactive glasses have drawn worldwide attention by virtue of the convenience and flexibility of this versatile synthesis method. In this review, the recent advances in sol–gel processed porous bioactive glasses in biomedical fields, especially for bone tissue regeneration applications have been comprehensively reviewed....

Tendons are vital to joint movement by connecting muscles to bones. Along with an increasing incidence of tendon injuries, tendon disorders can burden the quality of life of patients or the career of athletes. Current treatments involve surgical reconstruction and conservative therapy. Especially in the elderly population, tendon recovery requires...

Bone metastases are a frequent complication in prostate cancer, and several studies have shown that vitamin D deficiency promotes bone metastases. However, while many studies focus on vitamin D’s role in cell metabolism, the effect of chronically low vitamin D levels on bone tissue, i.e. insufficient mineralization of the tissue, has largely been i...

Focal early osteoarthritis (OA) or degenerative lesions account for 60% of treated cartilage defects each year. The current cell-based regenerative treatments have an increased failure rate for treating degenerative lesions compared to traumatic defects. Mesenchymal stem cells (MSCs) are an alternative cell source for treating early OA defects, due...

Objectives The aim was to investigate the impact of static compressive force (CF) application on human PDL-derived fibroblasts (HPDF) in vitro for up to 6 days on the expression of specific genes and to monitor cell growth and cell viability. Materials and methods CF of 2 g/cm² was applied on HPDFs for 1–6 days. On each day, gene expression (cFOS,...

So far unexplored corrosion of titanium silicide (Ti5Si3) surface with acidified hydrogen peroxide is of interest due to its potential use in improving osseointegration of titanium implants coated by titanium silicides. Detailed examination of corrosion products by FTIR, Raman and XP spectroscopy, electron microscopy, XRD, BET and light scattering...

Therapy options for ruptured Achilles tendons need to take into account the right balance of timing, amount and intensity of loading to ensure a sufficient biomechanical resilience of the healing tendon on the one hand, and to enable an adequate tensile stimulus on the other hand. However, biomechanical data of human Achilles tendons after rupture...

Tendons are dense connective tissues, which are critical for the integrity and function of our musculoskeletal system. During tendon aging and degeneration, tendon stem/progenitor cells (TSPCs) experience profound phenotypic changes with declined cellular functions that can be linked to the known increase in complications during tendon healing proc...

The poor healing capacity of tendons is known to worsen in the elderly. During tendon aging and degeneration, endogenous human tendon stem/progenitor cells (hTSPCs) experience profound pathological changes. Here, we explored a rejuvenation strategy for hTSPCs derived from aged/degenerated Achilles tendons (A-TSPCs) by providing three-dimensional (3...

In recent years, the sol-gel synthesis of porous glasses has drawn widespread attention owing to the convenience and versatility of the sol-gel method. The sol-gel synthesis process mainly involves hydrolysis and condensation of precursors followed by drying and stabilization. In the present study, silica-titania (Si-Ti) based porous glasses with d...

Integrity of the musculoskeletal system is essential for the transfer of muscular contraction force to the associated bones. Tendons and skeletal muscles intertwine, but on a cellular level, the myotendinous junctions (MTJs) display a sharp transition zone with a highly specific molecular adaption. The function of MTJs could go beyond a mere struct...

The purpose of this study was to evaluate the quality of surface contouring of chondromalacic cartilage by bipolar radio frequency energy using different treatment patterns in an animal model, as well as examining the impact of the treatment onto chondrocyte viability by two different methods. Our experiments were conducted on 36 fresh osteochondra...

The intervertebral disc (IVD) degeneration is thought to be closely related to ingrowth of new blood vessels. However, the impact of anti-angiogenic factors in the maintenance of IVD avascularity remains unknown. Tenomodulin (Tnmd) is a tendon/ligament-specific marker and anti-angiogenic factor with abundant expression in the IVD. It is still uncle...

In vitro chondrogenically differentiated mesenchymal stem cells (MSCs) have a tendency to undergo hypertrophy, mirroring the fate of transient “chondrocytes” in the growth plate. As hypertrophy would result in ossification, this fact limits their use in cartilage tissue engineering applications. During limb development, retinoic acid receptor (RAR)...

The biggest compartment of the musculoskeletal system is the tendons and ligaments. In particular, tendons are dense tissues connecting muscle to bone that are critical for the integrity, function and locomotion of this system. Due to the increasing age of our society and the overall rise in engagement in extreme and overuse sports, there is a grow...

Background: The anterior-cruciate-ligament (ACL) contains mesenchymal stem cells (ACL-MSCs), suggesting the feasibility of regenerative treatments of this tissue. The immortalization of isolated cells results in cell-lines applicable to develop cell-based therapies. Immortal cell lines eliminate the need for frequent cell isolation from donor tiss...

Osteoarthritis (OA) is a degenerative condition that involves the production of inflammatory cytokines (e.g., interleukin-1β (IL-1β), tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)) that stimulate degradative enzymes, matrix metalloproteinases (MMPs) and aggrecanases (ADAMTS) resulting in articular cartilage breakdown. The presence o...

Early osteoarthritis (OA), characterised by cartilage defects, is a degenerative disease that greatly affects the adult population. Cell-based tissue engineering methods are being explored as a solution for the treatment of these chondral defects. Chondrocytes are already in clinical use but other cell types with chondrogenic properties, such as me...

Tenomodulin (Tnmd) is predominantly expressed in tendon and ligament tissues. Loss of Tnmd in mice leads to a profound phenotype in vitro, characterized by reduced self-renewal but increased senescence of mouse tendon stem/progenitor cells (mTSPCs), as well as in vivo, by significantly impaired early tendon healing. Interestingly, injuried Achilles...

Articular cartilage covers the surface of synovial joints and enables joint movement. However, it is susceptible to progressive degeneration with age that can be accelerated by either previous joint injury or meniscectomy. This degenerative disease is known as osteoarthritis (OA) and it greatly affects the adult population. Cell-based tissue engine...

Tendon stem/progenitor cells (TSPC) are potential targets for regenerative medicine and the treatment of tendon injuries. The frequency of such injuries increases in elderly patients while the proportion of functional TSPCs in tendon tissue decreases, protracting tendon repair. Using atomic force microscopy (AFM), we show that cell stiffness and si...

The poor and slow healing capacity of tendons requires novel strategies to speed up the tendon repair process. Hence, new and promising developments in tendon tissue engineering have become increasingly relevant. Previously, we have established a tendon progenitor cell line via ectopic expression of the tendon-related basic helix-loop-helix (bHLH)...