Myoblast-derived ADAMTS-like 2 promotes skeletal muscle regeneration after injury.

Skeletal muscle regeneration and functional recovery after minor injuries requires the activation of muscle-resident myogenic muscle stem cells (i.e. satellite cells) and their subsequent differentiation into myoblasts, myocytes, and ultimately myofibers.

Regenerative potential of mouse neonatal intervertebral disc depends on collagen crosslink density.

Intervertebral disc (IVD) defects heal poorly and can cause back pain and disability. We identified that IVD herniation injury heals regeneratively in neonatal mice until postnatal day 14 (p14) and shifts to fibrotic healing by p28. This age coincides with the shift in expansive IVD growth from cell proliferation to matrix elaboration, implicating collagen crosslinking.

TNFR1-mediated senescence and lack of TNFR2-signaling limit human intervertebral disc cell repair in back pain conditions.

Poor intervertebral disc (IVD) healing causes IVD degeneration (IVDD) and progression to herniation and back pain. This study identified distinct roles of TNFα-receptors (TNFRs) in contributing to poor healing in painful IVDD. We first isolated IVDD tissue of back pain subjects and determined the complex pro-inflammatory mixture contained many chemokines for recruiting inflammatory cells.

The role of the complement system in disc degeneration and Modic changes.

Disc degeneration and vertebral endplate bone marrow lesions called Modic changes are prevalent spinal pathologies found in chronic low back pain patients. Their pathomechanisms are complex and not fully understood. Recent studies have revealed that complement system proteins and interactors are dysregulated in disc degeneration and Modic changes.

Combining adhesive and nonadhesive injectable hydrogels for intervertebral disc repair in an ovine discectomy model.

Background: Intervertebral disc (IVD) disorders (e.g., herniation) directly contribute to back pain, which is a leading cause of global disability.

Galectin-3 and RAGE differentially control advanced glycation endproduct-induced collagen damage in murine intervertebral disc organ culture.

Background: Back and neck pain are leading causes of global disability that are associated with intervertebral disc (IVD) degeneration. Causes of IVD degeneration are multifactorial, and diet, age, and diabetes have all been linked to IVD degeneration. Advanced glycation endproducts (AGEs) accumulate in the IVD as a result of aging, diet, and diabetes, and AGE accumulation in the IVD has been shown to induce oxidative stress and catabolic activity that result in collagen damage.

Teaching Tissue Repair Through an Inquiry-Based Learning Bioadhesives Module.

Bioadhesives are an important class of biomaterials for wound healing, hemostasis, and tissue repair. To develop the next generation of bioadhesives, there is a societal need to teach trainees about their design, engineering, and testing. This study designed, implemented, and evaluated a hands-on, inquiry-based learning (IBL) module to teach bioadhesives to undergraduate, master's, and PhD/postdoctoral trainees.

Lumbar endplate microfracture injury induces Modic-like changes, intervertebral disc degeneration and spinal cord sensitization - an in vivo rat model.

Background Context: Endplate (EP) injury plays critical roles in painful IVD degeneration since Modic changes (MCs) are highly associated with pain. Models of EP microfracture that progress to painful conditions are needed to better understand pathophysiological mechanisms and screen therapeutics.

Purpose: Establish in vivo rat lumbar EP microfracture model and assess crosstalk between IVD, vertebra and spinal cord.

Harmonization and standardization of nucleus pulposus cell extraction and culture methods.

Background: In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab-to-lab variability jeopardizes the much-needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources.

Orthogonal plating of distal femur fractures: A biomechanical comparison with plate-nail and parallel plating constructs.

Purpose: This study compared the biomechanical properties of orthogonal plating with plate-nail and parallel plating constructs for supracondylar distal femur fractures.

Methods: A supracondylar distal femur fracture was simulated using 15 synthetic osteoporotic femurs. Constructs included: (1) plate-nail (lateral locked distal femoral plate + retrograde intramedullary nail); (2) parallel plating (lateral locked distal femoral plate + medial 4.

Spinal Cord Sensitization and Spinal Inflammation from an In Vivo Rat Endplate Injury Associated with Painful Intervertebral Disc Degeneration.

Intervertebral disc (IVD) degeneration with Modic-like changes is strongly associated with pain. Lack of effective disease-modifying treatments for IVDs with endplate (EP) defects means there is a need for an animal model to improve understanding of how EP-driven IVD degeneration can lead to spinal cord sensitization. This rat in vivo study determined whether EP injury results in spinal dorsal horn sensitization (substance P, SubP), microglia (Iba1) and astrocytes (GFAP), and evaluated their relationship with pain-related behaviors, IVD degeneration, and spinal macrophages (CD68).

Lumbar endplate microfracture injury induces Modic-like changes, intervertebral disc degeneration and spinal cord sensitization - An In Vivo Rat Model.

: Endplate (EP) injury plays critical roles in painful IVD degeneration since Modic changes (MCs) are highly associated with pain. Models of EP microfracture that progress to painful conditions are needed to better understand pathophysiological mechanisms and screen therapeutics. : Establish in vivo rat lumbar EP microfracture model with painful phenotype.

Hydrogel-Embedded Poly(Lactic--Glycolic Acid) Microspheres for the Delivery of hMSC-Derived Exosomes to Promote Bioactive Annulus Fibrosus Repair.

Objective: Intervertebral disk degeneration is a prevalent postoperative complication after discectomy, underscoring the need to develop preventative and bioactive treatment strategies that decelerate degeneration and seal annulus fibrosus (AF) defects. Human mesenchymal stem cell-derived exosomes (MSC-Exos) hold promise for cell-free bioactive repair; however, their ability to promote AF repair is poorly understood. The objective of this study was to evaluate the ability of MSC-Exos to promote endogenous AF repair processes and integrate MSC-Exos within a biomaterial delivery system.

Comparison and optimization of sheep in vivo intervertebral disc injury model.

Background: The current standard of care for intervertebral disc (IVD) herniation, surgical discectomy, does not repair annulus fibrosus (AF) defects, which is partly due to the lack of effective methods to do so and is why new repair strategies are widely investigated and tested preclinically. There is a need to develop a standardized IVD injury model in large animals to enable comparison and interpretation across preclinical study results. The purpose of this study was to compare IVD injury models in sheep to determine which annulus fibrosus (AF) defect type combined with partial nucleus pulposus (NP) removal would better mimic degenerative human spinal pathologies.

Bone matrix quality in a developing high-fat diet mouse model is altered by RAGE deletion.

Overweightness and obesity in adolescents are epidemics linked to chronic low-grade inflammation and elevated fracture risk. The increased fracture risk observed in overweight/obese adolescence contrasts the traditional concept that high body mass is protective against fracture, and thus highlights the need to determine why weight gain becomes detrimental to fracture during growth and maturity. The Receptor for Advanced Glycation End products (RAGE) is a central inflammatory regulator that can influence bone metabolism.

Mechanisms and clinical implications of intervertebral disc calcification.

Low back pain is a leading cause of disability worldwide. Intervertebral disc (IVD) degeneration is often associated with low back pain but is sometimes asymptomatic. IVD calcification is an often overlooked disc phenotype that might have considerable clinical impact.

Development of an At-home Metal Corrosion Laboratory Experiment for STEM Outreach in Biomaterials During the Covid-19 Pandemic.

Due to the coronavirus disease 2019 (COVID-19) pandemic, many universities and outreach programs have switched to online learning platforms, which inhibits students from completing formative hands-on experiments. To address this, we developed a series of at-home experiments for undergraduate engineering students and adapted one of these experiments for outreach purposes. This experiment was well received by middle school students in the Young Eisner Scholars (YES) Program and resulted in significant learning gains by pre/post-test assessment.

Ex vivo biomechanical evaluation of Acute lumbar endplate injury and comparison to annulus fibrosus injury in a rat model.

Back pain is often associated with intervertebral disc (IVD) degeneration, and IVD degeneration phenotypes are commonly characterized by annulus fibrosus (AF)-driven and endplate (EP)-driven phenotypes. Few studies of EP injury exist in animal models, even though clinical studies show EP lesions are strongly associated with IVD pathology and pain. This project established an ex-vivo rat lumbar EP injury model and characterized effects of EP injury on motion segment biomechanical properties, as compared to AF injury, a common way of inducing IVD degeneration.

Notochordal Cell-Based Treatment Strategies and Their Potential in Intervertebral Disc Regeneration.

Chronic low back pain is the number one cause of years lived with disability. In about 40% of patients, chronic lower back pain is related to intervertebral disc (IVD) degeneration. The standard-of-care focuses on symptomatic relief, while surgery is the last resort.

Accelerometry Data Delineate Phases of Recovery and Supplement Patient-Reported Outcome Measures Following Lumbar Laminectomy.

Background: Patient-reported outcome measures (PROMs) are traditionally used to track recovery of patients after spine surgery. Wearable accelerometers have adjunctive value because of the continuous, granular, and objective data they provide. We conducted a prospective study of lumbar laminectomy patients to determine if time-series data from wearable accelerometers could delineate phases of recovery and compare accelerometry data to PROMs during recovery tracking.

Single-cell RNA-sequencing atlas of bovine caudal intervertebral discs: Discovery of heterogeneous cell populations with distinct roles in homeostasis.

Back and neck pain are significant healthcare burdens that are commonly associated with pathologies of the intervertebral disc (IVD). The poor understanding of the cellular heterogeneity within the IVD makes it difficult to develop regenerative IVD therapies. To address this gap, we developed an atlas of bovine (Bos taurus) caudal IVDs using single-cell RNA-sequencing (scRNA-seq).