Novel Method to Assess Macrophage Phenotype Using Eluted Media.

Introduction: Macrophages exist on a spectrum from pro-inflammatory (M1) to pro-healing (M2). Characterization of macrophage phenotype is important to understand tissue healing and response. The gold standard for assessing macrophage phenotypes is immunocytochemistry (ICC), which stains inducible Nitric Oxide Synthase (iNOS) and arginase (Arg1), the proteins secreted before nitrite and urea production.

Gait assessment in a female rat Sprague Dawley model of disc-associated low back pain.

Purpose: Gait disturbances are common in human low back pain (LBP) patients, suggesting potential applicability to rodent LBP models. This study aims to assess the influence of disc-associated LBP on gait in female Sprague Dawley rats and explore the utility of the open-source Gait Analysis Instrumentation and Technology Optimized for Rodents (GAITOR) suite as a potential alternative tool for spontaneous pain assessment in a previously established LBP model.

Materials And Methods: Disc degeneration was surgically induced using a one-level disc scrape injury method, and microcomputed tomography was used to assess disc volume loss.

Harvesting, Embedding, and Culturing Dorsal Root Ganglia in Multi-compartment Devices to Study Peripheral Neuronal Features.

The most common peripheral neuronal feature of pain is a lowered stimulation threshold or hypersensitivity of terminal nerves from the dorsal root ganglia (DRG). One proposed cause of this hypersensitivity is associated with the interaction between immune cells in the peripheral tissue and neurons. In vitro models have provided foundational knowledge in understanding how these mechanisms result in nociceptor hypersensitivity.

Identification of compounds that cause axonal dieback without cytotoxicity in dorsal root ganglia explants and intervertebral disc cells with potential to treat pain via denervation.

Low back pain, knee osteoarthritis, and cancer patients suffer from chronic pain. Aberrant nerve growth into intervertebral disc, knee, and tumors, are common pathologies that lead to these chronic pain conditions. Axonal dieback induced by capsaicin (Caps) denervation has been FDA-approved to treat painful neuropathies and knee osteoarthritis but with short-term efficacy and discomfort.

Type I collagen concentration affects neurite outgrowth of adult rat DRG explants by altering mechanical properties of hydrogels.

Type I collagen is a predominant fibrous protein that makes up the extracellular matrix. Collagen enhances cell attachment and is commonly used in three-dimensional culture systems, to mimic the native extracellular environment, for primary sensory neurons such as dorsal root ganglia (DRG). However, the effects of collagen concentration on adult rat DRG neurite growth have not been assessed in a physiologically relevant, three-dimensional culture.

Engineering a multicompartment in vitro model for dorsal root ganglia phenotypic assessment.

Despite the significant global prevalence of chronic pain, current methods to identify pain therapeutics often fail translation to the clinic. Phenotypic screening platforms rely on modeling and assessing key pathologies relevant to chronic pain, improving predictive capability. Patients with chronic pain often present with sensitization of primary sensory neurons (that extend from dorsal root ganglia [DRG]).

Encapsulation of Manganese Porphyrin in Chondroitin Sulfate-A Microparticles for Long Term Reactive Oxygen Species Scavenging.

Introduction: Oxidative stress due to excess reactive oxygen species (ROS) is related to many chronic illnesses including degenerative disc disease and osteoarthritis. MnTnBuOE-2-PyP (BuOE), a manganese porphyrin analog, is a synthetic superoxide dismutase mimetic that scavenges ROS and has established good treatment efficacy at preventing radiation-induced oxidative damage in healthy cells. BuOE has not been studied in degenerative disc disease applications and only few studies have loaded BuOE into drug delivery systems.

Axial hypersensitivity is associated with aberrant nerve sprouting in a novel model of disc degeneration in female Sprague Dawley rats.

Chronic low back pain is a global socioeconomic crisis and treatments are lacking in part due to inadequate models. Etiological research suggests that the predominant pathology associated with chronic low back pain is intervertebral disc degeneration. Various research teams have created rat models of disc degeneration, but the clinical translatability of these models has been limited by an absence of robust chronic pain-like behavior.

Apoptosis-Decellularized Peripheral Nerve Scaffold Allows Regeneration across Nerve Gap.

Peripheral nerve injury results in loss of motor and sensory function distal to the nerve injury and is often permanent in nerve gaps longer than 5 cm. Autologous nerve grafts (nerve autografts) utilize patients' own nerve tissue from another part of their body to repair the defect and are the gold standard in care. However, there is a limited autologous tissue supply, size mismatch between donor nerve and injured nerve, and morbidity at the site of nerve donation.

Injectable decellularized nucleus pulposus tissue exhibits neuroinhibitory properties.

Background: Chronic low back pain (LBP) is a leading cause of disability, but treatments for LBP are limited. Degeneration of the intervertebral disc due to loss of neuroinhibitory sulfated glycosaminoglycans (sGAGs) allows nerves from dorsal root ganglia to grow into the core of the disc. Treatment with a decellularized tissue hydrogel that contains sGAGs may inhibit nerve growth and prevent disc-associated LBP.

Matrix-Bound Nanovesicles: What Are They and What Do They Do?

Over the past 50 years, several different types of extracellular vesicles have been discovered including exosomes, microvesicles, and matrix vesicles. These vesicles are secreted by cells for specific purposes and contain cargo such as microRNA, cytokines, and lipids. A novel extracellular vesicle, the matrix-bound nanovesicle (MBV), has been recently discovered.

Extracellular Matrix Disparities in an Mutant Mouse Model of Congenital Heart Disease.

Congenital heart disease (CHD) affects almost one percent of all live births. Despite diagnostic and surgical reparative advances, the causes and mechanisms of CHD are still primarily unknown. The extracellular matrix plays a large role in cell communication, function, and differentiation, and therefore likely plays a role in disease development and pathophysiology.

Development of an in vitro intervertebral disc innervation model to screen neuroinhibitory biomaterials.

Pain originating from an intervertebral disc (discogenic pain) is a major source of chronic low back pain. Pathological innervation of the disc by pain-sensing nerve fibers is thought to be a key component of discogenic pain, so treatment with biomaterials that have the ability to inhibit neurite growth will greatly benefit novel disc therapeutics. Currently, disc therapeutic biomaterials are rarely screened for their ability to modulate nerve growth, mainly due to a lack of models to screen neuromodulation.

Oligonucleotide-functionalized hydrogels for sustained release of small molecule (aptamer) therapeutics.

Natural and synthetic hydrogels have been widely investigated as biomaterial scaffolds to promote tissue repair and regeneration. Nevertheless, the scaffold alone is often insufficient to drive new tissue growth, instead requiring continuous delivery of therapeutics, such as proteins or other biomolecules that work in concert with structural support provided by the scaffold. However, because of the high-water content, hydrogels tend to be permeable and cause rapid release of the encapsulated drug, which could lead to serious complications from local overdose and may result in the significant waste of encapsulated therapeutic(s).

Novel Sodium Deoxycholate-Based Chemical Decellularization Method for Peripheral Nerve.

Decellularized peripheral nerve has been proven to be an effective clinical intervention for peripheral nerve repair and a preclinical cell carrier after spinal cord injury. However, there are currently a lack of decellularization methods for peripheral nerve that remove cells and maintain matrix similar to the previously established, clinically translated technique (the Hudson method) that relies on the discontinued Triton X-200 detergent. Therefore, the aim of this study was to optimize a novel chemical decellularization method for peripheral nerves based on the currently available anionic detergent sodium deoxycholate.

Development of an apoptosis-assisted decellularization method for maximal preservation of nerve tissue structure.

Unlabelled: Preservation of tissue structure is often a primary goal when optimizing tissue and organ decellularization methods. Many current protocols nonetheless rely on detergents that aid extraction of cellular components but also damage tissue architecture. It may be more beneficial to leverage an innate cellular process such as apoptosis and promote cell removal without the use of damaging reagents.

The Open Source GAITOR Suite for Rodent Gait Analysis.

Locomotive changes are often associated with disease or injury, and these changes can be quantified through gait analysis. Gait analysis has been applied to preclinical studies, providing quantitative behavioural assessment with a reasonable clinical analogue. However, available gait analysis technology for small animals is somewhat limited.

Decellularized peripheral nerve supports Schwann cell transplants and axon growth following spinal cord injury.

Schwann cell (SC) transplantation has been comprehensively studied as a strategy for spinal cord injury (SCI) repair. SCs are neuroprotective and promote axon regeneration and myelination. Nonetheless, substantial SC death occurs post-implantation, which limits therapeutic efficacy.

Creation of an injectable in situ gelling native extracellular matrix for nucleus pulposus tissue engineering.

Background Context: Disc degeneration is the leading cause of low back pain and is often characterized by a loss of disc height, resulting from cleavage of chondroitin sulfate proteoglycans (CSPGs) present in the nucleus pulposus. Intact CSPGs are critical to water retention and maintenance of the nucleus osmotic pressure. Decellularization of healthy nucleus pulposus tissue has the potential to serve as an ideal matrix for tissue engineering of the disc because of the presence of native disc proteins and CSPGs.

Elementary Implantable Force Sensor: For Smart Orthopaedic Implants.

Implementing implantable sensors which are robust enough to maintain long term functionality inside the body remains a significant challenge. The ideal implantable sensing system is one which is simple and robust; free from batteries, telemetry, and complex electronics. We have developed an elementary implantable sensor for orthopaedic smart implants.

Implantable sensor technology: from research to clinical practice.

For decades, implantable sensors have been used in research to provide comprehensive understanding of the biomechanics of the human musculoskeletal system. These complex sensor systems have improved our understanding of the in vivo environment by yielding in vivo measurements of force, torque, pressure, and temperature. Historically, implants have been modified to be used as vehicles for sensors and telemetry systems.