Osthole ameliorates wear particle-induced osteogenic impairment by mitigating endoplasmic reticulum stress via PERK signaling cascade.

Background: Periprosthetic osteolysis and subsequent aseptic loosening are the leading causes of failure following total joint arthroplasty. Osteogenic impairment induced by wear particles is regarded as a crucial contributing factor in the development of osteolysis, with endoplasmic reticulum (ER) stress identified as a key underlying mechanism. Therefore, identifying potential therapeutic targets and agents that can regulate ER stress adaption in osteoblasts is necessary for arresting aseptic loosening.

Golgi pH elevation due to loss of V-ATPase subunit V0a2 function correlates with tissue-specific glycosylation changes and globozoospermia.

Loss-of-function variants in ATP6V0A2, encoding the trans Golgi V-ATPase subunit V0a2, cause wrinkly skin syndrome (WSS), a connective tissue disorder with glycosylation defects and aberrant cortical neuron migration. We used knock-out (Atp6v0a2) and knock-in (Atp6v0a2) mice harboring the R755Q missense mutation selectively abolishing V0a2-mediated proton transport to investigate the WSS pathomechanism. Homozygous mutants from both strains displayed a reduction of growth, dermis thickness, and elastic fiber formation compatible with WSS.

Incorporation of metal-doped silicate microparticles into collagen scaffolds combines chemical and architectural cues for endochondral bone healing.

Regeneration of large bone defects remains a clinical challenge until today. While existing biomaterials are predominantly addressing bone healing via direct, intramembranous ossification (IO), bone tissue formation via a cartilage phase, so-called endochondral ossification (EO) has been shown to be a promising alternative strategy. However, pure biomaterial approaches for EO induction are sparse and the knowledge how material components can have bioactive contribution to the required cartilage formation is limited.

Quality of lumbar paraspinal muscles in patients with chronic low back pain and its relationship to pain duration, pain intensity, and quality of life.

Objectives: To examine the relationship between the quality of paraspinal muscles and pain intensity, duration, and quality of life in patients with chronic low back pain (cLBP).

Methods: Between January 2022 and December 2023, 119 individuals with no-back pain (no-BP) and 136 cLBP patients were enrolled. Both groups underwent health surveys and magnetic resonance imaging.

Meta-analysis of proteomics data from osteoblasts, bone, and blood: Insights into druggable targets, active factors, and potential biomarkers for bone biomaterial design.

Non-healing bone defects are a pressing public health concern accounting for one main cause for decreased life expectancy and quality. An aging population accompanied with increasing incidence of comorbidities, foreshadows a worsening of this socio-economic problem. Conventional treatments for non-healing bone defects prove ineffective for 5%-10% of fractures.

Prognostic implications of a CD8 T to CD4T imbalance in mandibular fracture healing: a prospective analysis of immune profiles.

Introduction: Open reduction and fixation are the standard of care for treating mandibular fractures and usually lead to successful healing. However, complications such as delayed healing, non-union, and infection can compromise patient outcomes and increase healthcare costs. The initial inflammatory response, particularly the response involving specific CD8 T cell subpopulations, is thought to play a critical role in healing long bone fractures.

Risk-Adapted Use of Vancomycin in Secondary Scoliosis Surgery May Normalize SSI Risk in Surgical Correction of High-Risk Patients.

Intrawound application of vancomycin is becoming increasingly controversial for the prevention of surgical site infection (SSI). As children undergoing spinal fusion for secondary scoliosis are at high risk for SSIs, evidence regarding the impact of intraoperative vancomycin installation on SSI rates in these patients is of utmost importance. A single surgeon cohort of patients under 18 years of age undergoing surgery for secondary scoliosis in 2017 was analyzed with regard to the development of SSIs requiring surgical revision and adverse events.

Noninvasive bracing of acromioclavicular joint dislocations is not superior to early functional rehabilitation and not inferior to surgical stabilization in Rockwood type III and V injuries.

Background: Treatment of acromioclavicular joint (ACJ) separations remains controversial. Yet, conservative treatment has become more common even for high-grade injuries. Available conservative treatment does currently however not address the loss of anatomical joint integrity in Rockwood (RW) III and V injuries.

OMIBONE: Omics-driven computer model of bone regeneration for personalized treatment.

Treatment of bone fractures are standardized according to the AO classification, which mainly refers to the mechanical stabilization required in a given situation but neglect individual differences due to patient's healing potential or accompanying diseases. Specially in elderly or immune-compromised patients, the complexity of individual constrains on a biological as well as mechanical level are hard to account for. Here, we introduce a novel framework that allows to predict bone regeneration outcome using combined proteomic and mechanical analyses in a computer model.

Optimized intravital three-photon imaging of intact mouse tibia links plasma cell motility to functional states.

Intravital deep bone marrow imaging is crucial to studying cellular dynamics and functions but remains challenging, and minimally invasive methods are needed. We employed a high pulse-energy 1650 nm laser to perform three-photon microscopy , reaching ≈400 μm depth in intact mouse tibia. Repetition rates of 3 and 4 MHz allowed us to analyze motility patterns of fast and rare cells within unperturbed marrow and to identify a bi-modal migratory behavior for plasma cells.

Comparative study of CAD/CAM reconstruction and miniplates for patient-specific fixation in LCL-type mandibular reconstruction.

Objective: Miniplates offer superior clinical handling and facilitate postoperative removal after mandibular reconstruction but unfavorable load distribution under high stress has been shown. This study aimed to compare the clinical outcome of patient-specific 3D-printed (PS-3D) titanium miniplate with reconstruction plate fixation in three-segmental LCL-type reconstructions for the first time.

Methods: Patients undergoing three-segmental LCL-type mandibular reconstruction after malignant tumor resection between April 2017 and July 2023 were analyzed in a retrospective single-center study.

Increased cancellous bone mass accompanies decreased cortical bone mineral density and higher axial deformation in femurs of leptin-deficient obese mice.

Introduction: Leptin is a pleiotropic hormone that regulates food intake and energy homeostasis with enigmatic effects on bone development. It is unclear if leptin promotes or inhibits bone growth. The aim of this study was to characterize the micro-architecture and mechanical competence of femur bones of leptin-deficient mice.

Age-dependent flexion relaxation phenomenon in chronic low back pain patients.

Background: The flexion relaxation phenomenon (FRP) is characterized by suddenly reduced paraspinal muscle activity during full flexion. Previous studies showed significant differences in FRP and flexion angles in chronic low back pain (cLBP) patients compared to individuals without back pain (no-BP). However, the relationship between FRP and flexion angles remains insufficiently understood in older populations.

Targeting TGF-β signaling, oxidative stress, and cellular senescence rescues osteoporosis in gerodermia osteodysplastica.

GORAB is a key regulator of Golgi vesicle transport and protein glycanation. Loss of GORAB function in gerodermia osteodysplastica (GO) causes shortening of glycosaminoglycan chains, leading to extracellular matrix disorganization that results in wrinkled skin, osteoporosis and elevated TGF-β signaling. In this study, we investigated the role of TGF-β-signaling, oxidative stress, and resulting cellular senescence in the osteoporosis phenotype of GO.

The global evolution and impact of systems biology and artificial intelligence in stem cell research and therapeutics development: a scoping review.

Advanced bioinformatics analysis, such as systems biology (SysBio) and artificial intelligence (AI) approaches, including machine learning (ML) and deep learning (DL), is increasingly present in stem cell (SC) research. An approximate timeline on these developments and their global impact is still lacking. We conducted a scoping review on the contribution of SysBio and AI analysis to SC research and therapy development based on literature published in PubMed between 2000 and 2024.

Advanced therapies in orthopaedics.

Advanced therapies are expected to play a crucial role in supporting repair after injury, halting the degeneration of musculoskeletal tissue to enable and promote physical activity. Despite advancements, the progress in developing advanced therapies in orthopaedics lags behind specialties like oncology, since innovative regenerative treatment strategies fall short of their expectations in musculoskeletal clinical trials. Researchers should focus on understanding the mechanism of action behind the investigated target before conducting clinical trials.

Temporal regulation of BMP2 growth factor signaling in response to mechanical loading is linked to cytoskeletal and focal adhesion remodeling.

Biophysical cues have the ability to enhance cellular signaling response to Bone Morphogenetic Proteins, an essential growth factor during bone development and regeneration. Yet, therapeutic application of Bone Morphogenetic Protein 2 (BMP2) is restricted due to uncontrolled side effects. An understanding of the temporal characteristics of mechanically regulated signaling events and underlying mechanism is lacking.

Better clinical outcomes and lower triggering of inflammatory cytokines for allogeneic hematopoietic cell transplant recipients treated in home care versus hospital isolation - the Karolinska experience.

After allogeneic hematopoietic cell transplantation (Allo-HCT) and conditioning, patients are typically placed in isolated hospital rooms to prevent neutropenic infections. Since 1998, we've offered an alternative: home care for patients living within a one to two-hour drive of the hospital. In Sweden this approach includes daily visits by an experienced nurse and daily phone consultations with a unit physician.

Titanium vs PEO Surface-Modified Magnesium Plate Fixation in a Mandible Bone Healing Model in Sheep.

Titanium plates are the current gold standard for fracture fixation of the mandible. Magnesium alloys such as WE43 are suitable biodegradable alternatives due to their high biocompatibility and elasticity modulus close to those of cortical bone. By surface modification, the reagibility of magnesium and thus hydrogen gas accumulation per time are further reduced, bringing plate fixation with magnesium closer to clinical application.