Bioinspired Nanotopography for Combinatory Osseointegration and Antibacterial Therapy.

The ongoing global health has highlighted the critical issue of secondary infections, particularly antibiotic-resistant bacterial infections, which have been significant contributors to mortality rates. Orthopedic implants, while essential for trauma and orthopedic surgeries, are particularly susceptible to these infections, leading to severe complications and economic burdens. The traditional use of antibiotics in treating these infections poses further challenges including the risk of developing antibiotic-resistant bacteria.

A scaffold containing zinc oxide for Schwann cell-mediated axon growth.

Schwann cells (SCs) transplanted in damaged nervous tissue promote axon growth, which may support the recovery of function lost after injury. However, SC transplant-mediated axon growth is often limited and lacks direction.We have developed a zinc oxide (ZnO) containing fibrous scaffold consisting of aligned fibers of polycaprolactone (PCL) with embedded ZnO nanoparticles as a biodegradable, bifunctional scaffold for promoting and guiding axon growth.

Spasticity Predicts Motor Recovery for Patients with Subacute Motor Complete Spinal Cord Injury.

Objective: A motor complete spinal cord injury (SCI) results in the loss of voluntary motor control below the point of injury. Some of these patients can regain partial motor function through inpatient rehabilitation; however, there is currently no biomarker to easily identify which patients have this potential. Evidence indicates that spasticity could be that marker.

Multisite Hebbian Plasticity Restores Function in Humans with Spinal Cord Injury.

Objective: Spinal cord injury (SCI) damages synaptic connections between corticospinal axons and motoneurons of many muscles, resulting in devastating paralysis. We hypothesized that strengthening corticospinal-motoneuronal synapses at multiple spinal cord levels through Hebbian plasticity (i.e.

Electrospun fiber-mediated delivery of neurotrophin-3 mRNA for neural tissue engineering applications.

Aligned electrospun fibers provide topographical cues and local therapeutic delivery to facilitate robust peripheral nerve regeneration. mRNA delivery enables transient expression of desired proteins that promote axonal regeneration. However, no prior work delivers mRNA from electrospun fibers for peripheral nerve regeneration applications.

The Effects of the Combination of Mesenchymal Stromal Cells and Nanofiber-Hydrogel Composite on Repair of the Contused Spinal Cord.

A bone marrow-derived mesenchymal stromal cell (MSC) transplant and a bioengineered nanofiber-hydrogel composite (NHC) have been shown to stimulate nervous tissue repair in the contused spinal cord in rodent models. Here, these two modalities were combined to assess their repair effects in the contused spinal cord in adult rats. Cohorts of contused rats were treated with MSC in NHC (MSC-NHC), MSC in phosphate-buffered saline (MSC-PBS), NHC, or PBS injected into the contusion site at 3 days post-injury.

Paired corticospinal-motoneuronal stimulation and exercise after spinal cord injury.

Context: Rehabilitation after spinal cord injury (SCI) relies on the use of exercise training, which has limited functional gains. There is a need to develop more efficient approaches to facilitate recovery after SCI.

Methods: This review focuses on a neuromodulation method where transcranial magnetic stimulation (TMS) over the primary motor cortex is paired with transcutaneous electrical stimulation over a peripheral nerve to induce plasticity at corticospinal-motoneuronal synapses.

Distinct patterns of spasticity and corticospinal connectivity following complete spinal cord injury.

Key Points: Damage to corticospinal axons has implications for the development of spasticity following spinal cord injury (SCI). Here, we examined to what extent residual corticospinal connections and spasticity are present in muscles below the injury (quadriceps femoris and soleus) in humans with motor complete thoracic SCI. We found three distinct subgroups of people: participants with spasticity and corticospinal responses in the quadriceps femoris and soleus; participants with spasticity and corticospinal responses in the quadriceps femoris only; and participants with no spasticity or corticospinal responses in either muscle.

The Effect of Inflammatory Priming on the Therapeutic Potential of Mesenchymal Stromal Cells for Spinal Cord Repair.

Mesenchymal stromal cells (MSC) are used for cell therapy for spinal cord injury (SCI) because of their ability to support tissue repair by paracrine signaling. Preclinical and clinical research testing MSC transplants for SCI have revealed limited success, which warrants the exploration of strategies to improve their therapeutic efficacy. MSC are sensitive to the microenvironment and their secretome can be altered in vitro by exposure to different culture media.

Efficacy and time course of acute intermittent hypoxia effects in the upper extremities of people with cervical spinal cord injury.

Spinal cord injuries (SCI) disrupt neural pathways between the brain and spinal cord, causing impairment of motor function and loss of independent mobility. Spontaneous plasticity in spared neural pathways improves function but is often insufficient to restore normal function. One unique approach to augment plasticity in spinal synaptic pathways is acute intermittent hypoxia (AIH), meaning brief exposure to mild bouts of low oxygen, interspersed with normoxia.

The Potential of Corticospinal-Motoneuronal Plasticity for Recovery after Spinal Cord Injury.

Purpose Of Review: This review focuses on a relatively new neuromodulation method where transcranial magnetic stimulation over the primary motor cortex is paired with transcutaneous electrical stimulation over a peripheral nerve to induce plasticity at corticospinal-motoneuronal synapses.

Recent Findings: Recovery of sensorimotor function after spinal cord injury largely depends on transmission in the corticospinal pathway. Significantly damaged corticospinal axons fail to regenerate and participate in functional recovery.

Macrophage-Derived Inflammation Induces a Transcriptome Makeover in Mesenchymal Stromal Cells Enhancing Their Potential for Tissue Repair.

Pre-clinical and clinical studies revealed that mesenchymal stromal cell (MSC) transplants elicit tissue repair. Conditioning MSC prior to transplantation may boost their ability to support repair. We investigated macrophage-derived inflammation as a means to condition MSC by comprehensively analyzing their transcriptome and secretome.

Acute intermittent hypoxia boosts spinal plasticity in humans with tetraplegia.

Paired corticospinal-motoneuronal stimulation (PCMS) elicits spinal synaptic plasticity in humans with chronic incomplete cervical spinal cord injury (SCI). Here, we examined whether PCMS-induced plasticity could be potentiated by acute intermittent hypoxia (AIH), a treatment also known to induce spinal synaptic plasticity in humans with chronic incomplete cervical SCI. During PCMS, we used 180 pairs of stimuli where corticospinal volleys evoked by transcranial magnetic stimulation over the hand representation of the primary motor cortex were timed to arrive at corticospinal-motoneuronal synapses of the first dorsal interosseous (FDI) muscle ~1-2 ms before the arrival of antidromic potentials elicited in motoneurons by electrical stimulation of the ulnar nerve.

Aligned Fingolimod-Releasing Electrospun Fibers Increase Dorsal Root Ganglia Neurite Extension and Decrease Schwann Cell Expression of Promyelinating Factors.

Researchers are investigating the use of biomaterials with aligned guidance cues, like those provided by aligned electrospun fibers, to facilitate axonal growth across critical-length peripheral nerve defects. To enhance the regenerative outcomes further, these aligned fibers can be designed to provide local, sustained release of therapeutics. The drug fingolimod improved peripheral nerve regeneration in preclinical rodent models by stimulating a pro-regenerative Schwann cell phenotype and axonal growth.

The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord.

An injury to the spinal cord causes long-lasting loss of nervous tissue because endogenous nervous tissue repair and regeneration at the site of injury is limited. We engineered an injectable nanofiber-hydrogel composite (NHC) with interfacial bonding to provide mechanical strength and porosity and examined its effect on repair and neural tissue regeneration in an adult rat model of spinal cord contusion. At 28 days after treatment with NHC, the width of the contused spinal cord segment was 2-fold larger than in controls.

Laminin polymer treatment accelerates repair of the crushed peripheral nerve in adult rats.

Promoting axon growth after peripheral nerve injury may support recovery. Soluble laminin polymers formed at pH 4 (aLam) accelerate axon growth from adult dorsal root ganglion neurons in vitro. We used an adult rat model of a peripheral (peroneal) nerve crush to investigate whether an injection of aLam enhances axon growth and functional recovery in vivo.

Validation study of neurotrophin-3-releasing chitosan facilitation of neural tissue generation in the severely injured adult rat spinal cord.

It was previously reported that a tube holding chitosan carriers loaded with neurotrophin-3 (NT-3), after insertion into a 5 mm long transection gap in the adult rat spinal cord, triggered de novo neural tissue generation and functional recovery. Here, we report an effort to validate these findings using stringent blinding methodologies, which are crucial for robustness in reproducing biomedical studies. Radio frequency identification (RFID) chips were utilized to label rats that were randomly assigned into three experimental groups: transection with chitosan-NT-3 implant (C-NT3), transection only (T-controls), and laminectomy only (S-controls), blinding the experimenters to the treatments.

Mesenchymal Stem Cell-Macrophage Choreography Supporting Spinal Cord Repair.

Spinal cord injury results in destructive events that lead to tissue loss and functional impairments. A hallmark of spinal cord injury is the robust and persistent presence of inflammatory macrophages. Mesenchymal stem cells (MSCs) are known to benefit repair of the damaged spinal cord often associated with improved functional recovery.

Soluble laminin polymers enhance axon growth of primary neurons in vitro.

A substrate of laminin polymers formed at pH 4 (acidic pH-induced laminin; aLam) promotes neurite growth of embryonic rat cortical neurons better than a substrate of similar but structurally different laminin polymers formed at neutral pH (neutral pH-induced laminin; nLam). We investigated the effects of these laminin polymers, used as soluble supplements, on neurite growth of cultured adult rat primary dorsal root ganglion neurons. When added to the culture medium, aLam was found to promote neurite growth about twofold better than nLam.

Biomaterials for revascularization and immunomodulation after spinal cord injury.

Spinal cord injury (SCI) causes immediate damage to the nervous tissue accompanied by loss of motor and sensory function. The limited self-repair competence of injured nervous tissue underscores the need for reparative interventions to recover function after SCI. The vasculature of the spinal cord plays a crucial role in SCI and repair.

Extracellular matrix components as therapeutics for spinal cord injury.

There is no treatment for people with spinal cord injury that leads to significant functional improvements. The extracellular matrix is an intricate, 3-dimensional, structural framework that defines the environment for cells in the central nervous system. The components of extracellular matrix have signaling and regulatory roles in the fate and function of neuronal and non-neuronal cells in the central nervous system.

Diagnostic accuracy of evoked potentials for functional impairment after contusive spinal cord injury in adult rats.

Iatrogenic spinal cord injury (SCI) is a cause of potentially debilitating post-operative neurologic complications. Currently, intra-operative neurophysiological monitoring (IONM) via somatosensory evoked potentials and motor-evoked potentials is used to detect and prevent impending SCI. However, no empirically validated interventions exist to halt the progression of iatrogenic SCI once it is detected.

Large animal and primate models of spinal cord injury for the testing of novel therapies.

Large animal and primate models of spinal cord injury (SCI) are being increasingly utilized for the testing of novel therapies. While these represent intermediary animal species between rodents and humans and offer the opportunity to pose unique research questions prior to clinical trials, the role that such large animal and primate models should play in the translational pipeline is unclear. In this initiative we engaged members of the SCI research community in a questionnaire and round-table focus group discussion around the use of such models.

The role of brain-derived neurotrophic factor in bone marrow stromal cell-mediated spinal cord repair.

The ability of intraspinal bone marrow stromal cell (BMSC) transplants to elicit repair is thought to result from paracrine effects by secreted trophic factors including brain-derived neurotrophic factor (BDNF). Here we used gene therapy to increase or silence BDNF production in BMSCs to investigate the role of BDNF in BMSC-mediated neuroprotection. In a spinal cord organotypic culture, BMSC-conditioned medium significantly enhanced spinal motoneuron survival by 64% compared with culture medium only.