A Human Progenitor Cell-Based Tissue Engineered Intervertebral Disc.

Cell and tissue engineering therapies provide promise for regenerating damaged intervertebral disc (IVD) tissue and resolving the low back pain that often accompanies it. However, these treatments remain experimental and unavailable for patients. Furthermore, the large body of work characterizing and utilizing mesenchymal stromal cells (MSCs) for these applications has, unfortunately, not resulted in any FDA-approved spinal therapies.

Synovial changes in osteoarthritis: symptom or disease driver?

Osteoarthritis (OA), long regarded as simply a disease of articular cartilage degeneration, has increasingly been recognized as a complex disorder involving multiple joint tissues, including the synovium. This review explores the emerging evidence that synovial changes seen in OA are not merely secondary to cartilage breakdown but may actively drive OA progression. We detail the physiological role of the synovium in joint homeostasis and highlight pathological remodeling processes, such as synovial hyperplasia, immune cell infiltration, and fibroblast activation, that contribute to joint degeneration.

Revealing the biophysics of lamina-associated domain formation by integrating theoretical modeling and high-resolution imaging.

Chromatin-lamina interactions regulate gene activity by forming lamina-associated domains (LADs), which contribute to cellular identity through gene repression. However, the strength of these interactions and their responsiveness to environmental cues remain unclear. Here, we develop a theoretical framework to predict LAD morphology in human mesenchymal stem cells (MSCs), whose differentiation potential depends on the stiffness of the microenvironment.

Engineering kidney developmental trajectory using culture boundary conditions.

Kidney explants are traditionally cultured at air-liquid interfaces, which disrupts 3D tissue structure and limits interpretation of developmental data. Here we develop a 3D culture technique using hydrogel embedding to capture kidney morphogenesis in real time. 3D culture better approximates in vivo-like niche spacing and tubule dynamics, as well as branching defects under control conditions and GDNF-RET signaling perturbations.

O-SNAP: A comprehensive pipeline for spatial profiling of chromatin architecture.

We present O-SNAP (Objective Single-Molecule Nuclear Architecture Profiler), a comprehensive pipeline for the automated extraction, comparison, and classification of nuclear features from single-molecule localization microscopy (SMLM) data. O-SNAP quantifies 144 interpretable, biologically grounded spatial features describing chromatin organization or histone mark distributions at nanoscale resolution. The pipeline includes modules for pairwise comparison of features using volcano plots, feature set enrichment analysis, robust feature selection and classification of cell states, and pseudotime trajectory inference.

Therapeutic Implants: Mechanobiologic Enhancement of Osteogenic, Angiogenic, and Myogenic Responses in Human Mesenchymal Stem Cells on 3D-Printed Titanium Truss.

This study investigates the effect of mechanotransduction on human mesenchymal stem cells (hMSCs) attached to structural elements of an implant, specifically a titanium truss element. It is found that surface features generated by 3D printing technology promote osteogenic activity, comparable to conventional treatments such as acid etching. Cell morphology and differentiation are evaluated using test coupons with either smooth or rough surface features.

CD14 plays a critical role in pain and inflammation across multiple models of post-traumatic osteoarthritis.

Unlabelled: Inflammation is a primary driver of osteoarthritis (OA), and no therapies exist to halt or delay disease progression or substantially ameliorate the chronic pain, inflammation and disability that are characteristic of disease. Soluble CD14 (sCD14), a co-factor that enhances inflammatory toll-like receptor signaling, is present in synovial fluid in patients with OA and positively associates with joint space narrowing, synovial macrophage content, and pain. In this study, we show that increased sCD14 within human synovial fluid correlates with joint effusion volume and increased knee hyperalgesia.

Multi-Scale Analysis of Regional Pathology in the Human Trapezium During Osteoarthritis Progression.

Trapeziometacarpal (TMC) osteoarthritis (OA) is a prevalent condition that significantly impacts hand function and quality of life. In this study we sought to close gaps in knowledge related to the initiation and progression of TMC OA on the tissue scale by evaluating the morphology and gross appearance, wear patterns, mechanical properties, subchondral bone morphology, and histological characteristics of the tissue across a spectrum of disease severity and by correlating each of these properties to the clinically assessed radiographic grade. Thirty-two cadaveric hand specimens were first assigned a radiographic grade by three hand surgeons.

In Vivo Measurements Reveal Increased Nucleus Pulposus Lactate and Oxygen Concentrations in a Goat Model of Intervertebral Disc Degeneration.

Introduction: Intervertebral disc degeneration is strongly implicated as a cause of low back pain. Although the precise pathophysiological mechanisms remain elusive, perturbations in nutrition that adversely impact the cellular microenvironment of the central nucleus pulposus (NP) may be contributing factors. A comprehensive understanding of this microenvironment, including changes in nutrient availability as a function of degeneration, is critical for the development of effective cell-based treatments.

Structure, Mechanics, and Mechanobiology of Fibrocartilage Pericellular Matrix Mediated by Type V Collagen.

The pericellular matrix (PCM) is the immediate microniche surrounding cells in various tissues, regulating matrix turnover, cell-matrix interactions, and disease. This study elucidates the structure-mechanical properties and mechanobiology of the PCM in fibrocartilage, using the murine meniscus as the model. The fibrocartilage PCM is comprised of thin, randomly oriented collagen fibrils that entrap proteoglycans, contrasting with the densely packed, highly aligned collagen fibers in the bulk extracellular matrix (ECM).

Degradable poly-lactic-co-glycolic acid and non-degradable polymer implants result in similar fracture healing at early timepoints.

Background: Although rigid interfragmentary fixation is required for fracture repair, overly stiff implants are known to cause stress shielding which ultimately inhibits healing. While gradual dynamization of the fracture site both accelerates and improves osteogenesis, this approach requires external fixators or secondary surgeries. This study leverages biodegradable implants as mechanisms of gradual, passive dynamization during fracture healing.

Precision repair of zone-specific meniscal injuries using a tunable extracellular matrix-based hydrogel system.

Meniscus injuries present significant therapeutic challenges due to their limited self-healing capacity and the diverse biological and mechanical properties across the tissue. Conventional repair strategies do not replicate the complex zonal characteristics within the meniscus, resulting in suboptimal outcomes. In this study, we introduce an innovative fetal/adult and stiffness-tunable meniscus decellularized extracellular matrix (DEM)-based hydrogel system designed for precision repair of heterogeneous, zonal-dependent meniscus injuries.

Annulus Fibrosus Repair via Interpenetration of a Non-Woven Scaffold Supports Tissue Integration and Prevents Re-Herniation.

Background: Current surgical management of intervertebral disc herniation often fails to adequately address the risk of recurrence, primarily due to the disc's limited regenerative capacity. Regenerative, biomaterial-based approaches for tissue augmentation, while showing preclinical promise, have consistently failed to meet the extreme mechanical demands of the intervertebral disc, impeding their clinical translation.

Methods: In this study, we introduce a novel annulus repair strategy that employs the mechanical interpenetration of a non-woven PET scaffold into intervertebral disc tissue to resist reherniation.

Arthroscopic synovitis severity scoring in canine stifles with cranial cruciate ligament disease.

Objective: To investigate the occurrence, degree, and risk factors associated with arthroscopic stifle joint synovitis in dogs with cranial cruciate ligament (CCL) disease.

Study Design: Retrospective, observational study.

Sample Population: Canine CCL disease (n = 163) from 149 dogs and their arthroscopic video recordings.

Engineering kidney developmental trajectory using culture boundary conditions.

Kidney explant cultures are traditionally carried out at air-liquid interfaces, which disrupts 3D tissue structure and limits interpretation of developmental data. To overcome this limitation, we developed a 3D culture technique using hydrogel embedding to capture morphogenesis in real time. We show that 3D culture better approximates -like niche spacing and dynamic tubule tip rearrangement, as well as -like presentation of branching defects under perturbations to glial cell-derived neurotrophic factor (GDNF)- RE arranged during T ransfection (RET) tyrosine kinase signaling.

Restoration of physiologic loading after engineered disc implantation mitigates immobilization-induced facet joint and paraspinal muscle degeneration.

Intervertebral disc degeneration is commonly associated with back and neck pain, and standard surgical treatments do not restore spine function. Replacement of the degenerative disc with a living, tissue-engineered construct has the potential to restore normal structure and function to the spine. Toward this goal, our group developed endplate-modified disc-like angle-ply structures (eDAPS) that recapitulate the native structure and function of the disc.

Learning on a Limb: An outreach module to engage high school students in orthopaedics.

Orthopaedic researchers need new strategies for engaging underrepresented minority (URM) students. Our field has demonstrated noticeable gaps in racial, ethnic, and gender diversity, which inhibit our ability to innovate and combat the severe socioeconomic burden of musculoskeletal disorders. Towards this goal, we designed, implemented, and evaluated Learning on a Limb (LoaL), an orthopaedic research outreach module to teach URM high school students about orthopaedic research.

Learning on a Limb: An outreach module to engage high school students in orthopaedics.

Orthopaedic researchers need new strategies for engaging diverse students. Our field has demonstrated noticeable gaps in racial, ethnic, and gender diversity, which inhibit our ability to innovate and combat the severe socioeconomic burden of musculoskeletal disorders. Towards this goal, we designed, implemented, and evaluated Learning on a Limb, an orthopaedic research outreach module to teach diverse high school students about orthopaedic research.

Interleukin receptor therapeutics attenuate inflammation in canine synovium following cruciate ligament injury.

Objective: In the knee, synovial fibrosis after ligamentous injury is linked to progressive joint pain and stiffness. The objective of this study was to evaluate changes in synovial architecture, mechanical properties, and transcriptional profiles following naturally occurring cruciate ligament injury in canines and to test potential therapeutics that target drivers of synovial inflammation and fibrosis.

Design: Synovia from canines with spontaneous cruciate ligament tears and from healthy knees were assessed via histology (n = 10/group) and micromechanical testing (n = 5/group) to identify changes in tissue architecture and stiffness.

Structure-Mechanics Principles and Mechanobiology of Fibrocartilage Pericellular Matrix: A Pivotal Role of Type V Collagen.

The pericellular matrix (PCM) is the immediate microniche surrounding resident cells in various tissue types, regulating matrix turnover, cell-matrix cross-talk and disease initiation. This study elucidated the structure-mechanical properties and mechanobiological functions of the PCM in fibrocartilage, a family of connective tissues that sustain complex tensile and compressive loads in vivo. Studying the murine meniscus as the model tissue, we showed that fibrocartilage PCM contains thinner, random collagen fibrillar networks that entrap proteoglycans, a structure distinct from the densely packed, highly aligned collagen fibers in the bulk extracellular matrix (ECM).

Revealing the Biophysics of Lamina-Associated Domain Formation by Integrating Theoretical Modeling and High-Resolution Imaging.

The interactions between chromatin and the nuclear lamina orchestrate cell type-specific gene activity by forming lamina-associated domains (LADs) which preserve cellular characteristics through gene repression. However, unlike the interactions between chromatin segments, the strength of chromatin-lamina interactions and their dependence on cellular environment are not well understood. Here, we develop a theory to predict the size and shape of peripheral heterochromatin domains by considering the energetics of chromatin-chromatin interactions, the affinity between chromatin and the nuclear lamina and the kinetics of methylation and acetylation9in human mesenchymal stem cells (hMSCs).