Micro-patterned cell populations as advanced pharmaceutical drugs with precise functional control.

Human cells are both advanced pharmaceutical drugs and 'drug deliverers'. However, functional control prior to or after cell implantation remains challenging. Micro-patterning cells through geometrically defined adhesion sites allows controlling morphogenesis, polarity, cellular mechanics, proliferation, migration, differentiation, stemness, cell-cell interactions, collective cell behavior, and likely immuno-modulatory properties.

Rebalance of the Polyamine Metabolism Suppresses Oxidative Stress and Delays Senescence in Nucleus Pulposus Cells.

Intervertebral disk degeneration (IDD) is a major cause of low back pain that becomes a prevalent age-related disease. However, the pathophysiological processes behind IDD are rarely known. Here, we used bioinformatics analysis based on the microarray datasets (GSE34095) to identify the differentially expressed genes (DEGs) as biomarkers and therapeutic targets in degenerated discs.

Mechanical Analysis and Corrosion Analysis of Zinc Alloys for Bioabsorbable Implants for Osteosynthesis.

Zinc alloys have recently been researched intensely for their great properties as bioabsorbable implants for osteosynthesis. Pure zinc (Zn) itself has relatively poor strength, which makes it insufficient for most clinical use. Research has already proven that the mechanical strength of zinc can be enhanced significantly by alloying it with silver.

Regenerative Potential of Platelet Concentrate Lysate in Mechanically Injured Cartilage and Matrix-Associated Chondrocyte Implantation In Vitro.

Adjuvant therapy in autologous chondrocyte implantation (ACI) can control the post-traumatic environment and guide graft maturation to support cartilage repair. To investigate both aspects, we examined potential chondro-regenerative effects of lysed platelet concentrate (PC) and supplementary interleukin 10 (IL-10) on mechanically injured cartilage and on clinically used ACI scaffolds. ACI remnants and human cartilage explants, which were applied to an uniaxial unconfined compression as injury model, were treated with human IL-10 and/or PC from thrombocyte concentrates.

Trauma patients with SARS-CoV-2 in German ICUs during the 2nd wave of the COVID-19 pandemic.

Purpose: In January and February 2021, about 4000 severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) positive patients were treated daily in German intensive care units (ICUs). The number of SARS-CoV-2-positive ICU patients with trauma, however, is not known and neither whether the trauma itself or COVID-19 causes the critical illness.

Methods: A total of 173 German ICUs, representing 3068 ICU beds, participated in a survey developed by the Trauma Section of the German Interdisciplinary Association of Intensive Care Medicine (DIVI).

Integrins, cadherins and channels in cartilage mechanotransduction: perspectives for future regeneration strategies.

Articular cartilage consists of hyaline cartilage, is a major constituent of the human musculoskeletal system and has critical functions in frictionless joint movement and articular homoeostasis. Osteoarthritis (OA) is an inflammatory disease of articular cartilage, which promotes joint degeneration. Although it affects millions of people, there are no satisfying therapies that address this disease at the molecular level.

Thromboembolic complications among multiple injured patients with pelvic injuries: identifying risk factors for possible patient-tailored prophylaxis.

Background: Patients with pelvic and/or acetabular fractures are at high risk of developing thromboembolic (TE) complications. In our study we investigate TE complications and the potential negative effects of concomitant pelvic or acetabular injuries in multiple injured patients according to pelvic/acetabular injury severity and fracture classification.

Methods: The TraumaRegister DGU® was analyzed between 2010 and 2019.

A Method for the Evaluation of Early Osseointegration of Implant Materials Ex Vivo: Human Bone Organ Model.

In the present work, an ex vivo organ model using human bone (explant) was developed for the evaluation of the initial osseointegration behavior of implant materials. The model was tested with additive manufactured Ti6Al4V test substrates with different 3D geometries. Explants were obtained from patients who underwent total knee replacement surgery.

Effect of expansion media and fibronectin coating on growth and chondrogenic differentiation of human bone marrow-derived mesenchymal stromal cells.

In the field of regenerative medicine, considerable advances have been made from the technological and biological point of view. However, there are still large gaps to be filled regarding translation and application of mesenchymal stromal cell (MSC)-based therapies into clinical practice. Indeed, variables such as cell type, unpredictable donor variation, and expansion/differentiation methods lead to inconsistencies.

The future of basic science in orthopaedics and traumatology: Cassandra or Prometheus?

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. Reflecting the complex and intertwined underlying mechanisms, cooperative research in this field has discovered important mechanisms on the molecular, cellular and organ levels, which subsequently led to innovative diagnostic and therapeutic strategies that reduced individual suffering as well as the burden on the society.

Architecture-Promoted Biomechanical Performance-Tuning of Tissue-Engineered Constructs for Biological Intervertebral Disc Replacement.

Background: Biological approaches to intervertebral disc (IVD) restoration and/or regeneration have become of increasing interest. However, the IVD comprises a viscoelastic system whose biological replacement remains challenging. The present study sought to design load-sharing two-component model systems of circular, nested, concentric elements reflecting the nucleus pulposus and annulus fibrosus.

Exploration of changes in spatial chondrocyte organisation in human osteoarthritic cartilage by means of 3D imaging.

Using two-dimensional top-down view microscopy, researchers have recently described chondrocytes as being spatially arranged in distinct patterns such as strings, double strings, and small and large clusters. Because of the seeming association of these changes with tissue degeneration, they have been proposed as an image-based biomarker for early osteoarthritis (OA) staging. The aim of our study was to investigate the spatial arrangement of chondrocytes in human articular cartilage in a 3D fashion and to evaluate the 3D changes of these patterns in the context of local tissue destruction.

Dexamethasone Induces Changes in Osteogenic Differentiation of Human Mesenchymal Stromal Cells via and , but Not .

Despite the huge body of research on osteogenic differentiation and bone tissue engineering, the translation potential of in vitro results still does not match the effort employed. One reason might be that the protocols used for in vitro research have inherent pitfalls. The synthetic glucocorticoid dexamethasone is commonly used in protocols for trilineage differentiation of human bone marrow mesenchymal stromal cells (hBMSCs).

Identification of a clinical signature predictive of differentiation fate of human bone marrow stromal cells.

Background: Transplantation of human bone marrow stromal cells (hBMSCs) is a promising therapy for bone regeneration due to their ability to differentiate into bone forming osteoblastic cells. However, transplanted hBMSCs exhibit variable capacity for bone formation resulting in inconsistent clinical outcome. The aim of the study was to identify a set of donor- and cell-related characteristics that detect hBMSCs with optimal osteoblastic differentiation capacity.

Inverse 3D Printing with Variations of the Strand Width of the Resulting Scaffolds for Bone Replacement.

The objective of this study was to vary the wall thicknesses and pore sizes of inversely printed 3D molded bodies. Wall thicknesses were varied from 1500 to 2000 to 2500 µm. The pores had sizes of 500, 750 and 1000 µm.

The intervertebral disc from embryonic development to disc degeneration: insights into spatial cellular organization.

Background Context: Low back pain is commonly attributed to intervertebral disc (IVD) degeneration. IVD resembles articular cartilage in its biochemical and cellular composition in many ways. For articular cartilage, degeneration stage-specific characteristic spatial chondrocyte patterns have recently been described.

Articular Chondrocyte Phenotype Regulation through the Cytoskeleton and the Signaling Processes That Originate from or Converge on the Cytoskeleton: Towards a Novel Understanding of the Intersection between Actin Dynamics and Chondrogenic Function.

Numerous studies have assembled a complex picture, in which extracellular stimuli and intracellular signaling pathways modulate the chondrocyte phenotype. Because many diseases are mechanobiology-related, this review asked to what extent phenotype regulators control chondrocyte function through the cytoskeleton and cytoskeleton-regulating signaling processes. Such information would generate leverage for advanced articular cartilage repair.

Mechanical Properties of the Composite Material consisting of β-TCP and Alginate-Di-Aldehyde-Gelatin Hydrogel and Its Degradation Behavior.

This work aimed to determine the influence of two hydrogels (alginate, alginate-di-aldehyde (ADA)/gelatin) on the mechanical strength of microporous ceramics, which have been loaded with these hydrogels. For this purpose, the compressive strength was determined using a Zwick Z005 universal testing machine. In addition, the degradation behavior according to ISO EN 10993-14 in TRIS buffer pH 5.

An Evidence-Based Systematic Review of Human Knee Post-Traumatic Osteoarthritis (PTOA): Timeline of Clinical Presentation and Disease Markers, Comparison of Knee Joint PTOA Models and Early Disease Implications.

Understanding the causality of the post-traumatic osteoarthritis (PTOA) disease process of the knee joint is important for diagnosing early disease and developing new and effective preventions or treatments. The aim of this review was to provide detailed clinical data on inflammatory and other biomarkers obtained from patients after acute knee trauma in order to (i) present a timeline of events that occur in the acute, subacute, and chronic post-traumatic phases and in PTOA, and (ii) to identify key factors present in the synovial fluid, serum/plasma and urine, leading to PTOA of the knee in 23-50% of individuals who had acute knee trauma. In this context, we additionally discuss methods of simulating knee trauma and inflammation in in vivo, ex vivo articular cartilage explant and in vitro chondrocyte models, and answer whether these models are representative of the clinical inflammatory stages following knee trauma.

Proof-of-concept for the detection of early osteoarthritis pathology by clinically applicable endomicroscopy and quantitative AI-supported optical biopsy.

Objective: Clinical trials for osteoarthritis (OA), the leading cause of global disability, are unable to pinpoint the early, potentially reversible disease with clinical technology. Hence, disease-modifying drug candidates cannot be tested early in the disease. To overcome this obstacle, we asked whether early OA-pathology detection is possible with current clinical technology.

The variance of clavicular surface morphology is predictable: an analysis of dependent and independent metadata variables.

Background: The anatomy of the clavicle is specific and varied in reference to its topography and shape. These anatomic characteristics play an important role in the open treatment of clavicle fractures. The complex and variable topography creates challenges for implant placement, contouring, and position.

Mechanotransduction and Stiffness-Sensing: Mechanisms and Opportunities to Control Multiple Molecular Aspects of Cell Phenotype as a Design Cornerstone of Cell-Instructive Biomaterials for Articular Cartilage Repair.

Since material stiffness controls many cell functions, we reviewed the currently available knowledge on stiffness sensing and elucidated what is known in the context of clinical and experimental articular cartilage (AC) repair. Remarkably, no stiffness information on the various biomaterials for clinical AC repair was accessible. Using mRNA expression profiles and morphology as surrogate markers of stiffness-related effects, we deduced that the various clinically available biomaterials control chondrocyte (CH) phenotype well, but not to equal extents, and only in non-degenerative settings.