Innervated Coculture Device to Model Peripheral Nerve-Mediated Fibroblast Activation.

Cutaneous wound healing is a complex process involving various cellular and molecular interactions, resulting in the formation of a collagen-rich scar with imperfect function and morphology. Dermal fibroblasts are crucial to successful wound healing, migrating to the wound site where they are activated to provide extracellular matrix remodeling and wound closure. Peripheral nerves have been shown to play an important role in wound healing, with loss or damage to these nerves often leading to impaired healing and the formation of chronic nonhealing wounds.

Biophysical control of plasticity and patterning in regeneration and cancer.

Cells and tissues display a remarkable range of plasticity and tissue-patterning activities that are emergent of complex signaling dynamics within their microenvironments. These properties, which when operating normally guide embryogenesis and regeneration, become highly disordered in diseases such as cancer. While morphogens and other molecular factors help determine the shapes of tissues and their patterned cellular organization, the parallel contributions of biophysical control mechanisms must be considered to accurately predict and model important processes such as growth, maturation, injury, repair, and senescence.

Neural dependency in wound healing and regeneration.

In response to injury, humans and many other mammals form a fibrous scar that lacks the structure and function of the original tissue, whereas other vertebrate species can spontaneously regenerate damaged tissues and structures. Peripheral nerves have been identified as essential mediators of wound healing and regeneration in both mammalian and nonmammalian systems, interacting with the milieu of cells and biochemical signals present in the post-injury microenvironment. This review examines the diverse functions of peripheral nerves in tissue repair and regeneration, specifically during the processes of wound healing, blastema formation, and organ repair.

Sensory nerves enhance triple-negative breast cancer invasion and metastasis via the axon guidance molecule PlexinB3.

In breast cancer, nerve presence has been correlated with more invasive disease and worse prognosis, yet the mechanisms by which different types of peripheral nerves drive tumor progression remain poorly understood. In this study, we identified sensory nerves as more abundant in human triple-negative breast cancer (TNBC) tumors. Co-injection of sensory neurons isolated from the dorsal root ganglia (DRG) of adult female mice with human TNBC cells in immunocompromised mice increased the number of lung metastases.

Potassium channel-driven bioelectric signalling regulates metastasis in triple-negative breast cancer.

Background: There is a critical need to better understand the mechanisms that drive local cell invasion and metastasis to develop new therapeutics targeting metastatic disease. Bioelectricity is an important mediator of cellular processes and changes in the resting membrane potential (RMP) are associated with increased cancer cell invasion. However, whether the RMP can be used to target invading cancer cells is unknown.

Beyond Neurons: Long Distance Communication in Development and Cancer.

Cellular communication is important in all aspects of tissue and organism functioning, from the level of single cells, two discreet populations, and distant tissues of the body. Long distance communication networks integrate individual cells into tissues to maintain a complex organism during development, but when communication between cells goes awry, disease states such as cancer emerge. Herein we discuss the growing body of evidence suggesting that communication methods known to be employed by neurons, also exist in other cell types.

Biomaterial-based cell delivery strategies to promote liver regeneration.

Chronic liver disease and cirrhosis is a widespread and untreatable condition that leads to lifelong impairment and eventual death. The scarcity of liver transplantation options requires the development of new strategies to attenuate disease progression and reestablish liver function by promoting regeneration. Biomaterials are becoming an increasingly promising option to both culture and deliver cells to support in vivo viability and long-term function.

An Injectable Hyaluronan-Methylcellulose (HAMC) Hydrogel Combined with Wharton's Jelly-Derived Mesenchymal Stromal Cells (WJ-MSCs) Promotes Degenerative Disc Repair.

Intervertebral disc (IVD) degeneration is one of the predominant causes of chronic low back pain (LBP), which is a leading cause of disability worldwide. Despite substantial progress in cell therapy for the treatment of IVD degeneration, significant challenges remain for clinical application. Here, we investigated the effectiveness of hyaluronan-methylcellulose (HAMC) hydrogels loaded with Wharton's Jelly-derived mesenchymal stromal cell (WJ-MSCs) in vitro and in a rat coccygeal IVD degeneration model.

The need for improved emotional support: A pilot online survey of Australian women's access to healthcare services and support at the time of miscarriage.

Problem: Women need improved emotional support from healthcare professionals following miscarriage.

Background: Significant psychological morbidity can result following miscarriage and may be exacerbated by poor support experiences. Women frequently report high levels of dissatisfaction with healthcare support at this time.

Bioelectric Control of Metastasis in Solid Tumors.

As the leading cause of death in cancer, there is an urgent need to develop treatments to target the dissemination of primary tumor cells to secondary organs, known as metastasis. Bioelectric signaling has emerged in the last century as an important controller of cell growth, and with the development of current molecular tools we are now beginning to identify its role in driving cell migration and metastasis in a variety of cancer types. This review summarizes the currently available research for bioelectric signaling in solid tumor metastasis.

Injectable hydrogel enables local and sustained co-delivery to the brain: Two clinically approved biomolecules, cyclosporine and erythropoietin, accelerate functional recovery in rat model of stroke.

Therapeutic delivery to the brain is limited by the blood-brain barrier and is exacerbated by off-target effects associated with systemic delivery, thereby precluding many potential therapies from even being tested. Given the systemic side effects of cyclosporine and erythropoietin, systemic administration would be precluded in the context of stroke, leaving only the possibility of local delivery. We wondered if direct delivery to the brain would allow new reparative therapeutics, such as these, to be identified for stroke.

Defined extracellular ionic solutions to study and manipulate the cellular resting membrane potential.

All cells possess an electric potential across their plasma membranes and can generate and receive bioelectric signals. The cellular resting membrane potential (RMP) can regulate cell proliferation, differentiation and apoptosis. Current approaches to measure the RMP rely on patch clamping, which is technically challenging, low-throughput and not widely available.

Local delivery of stabilized chondroitinase ABC degrades chondroitin sulfate proteoglycans in stroke-injured rat brains.

Central nervous system (CNS) injuries, such as stroke and spinal cord injuries, result in the formation of a proteoglycan-rich glial scar, which acts as a barrier to axonal regrowth and limits the regenerative capacity of the CNS. Chondroitinase ABC (ChABC) is a potent bacterial enzyme that degrades the chondroitin sulfate proteoglycan (CSPG) component of the glial scar and promotes tissue recovery; however, its use is significantly limited by its inherent instability at physiological temperatures. Here, we demonstrate that ChABC can be stabilized using site-directed mutagenesis and covalent modification with poly(ethylene glycol) chains (i.

Local Delivery of Brain-Derived Neurotrophic Factor Enables Behavioral Recovery and Tissue Repair in Stroke-Injured Rats.

We developed a biocomposite that can be mixed with brain-derived neurotrophic factor (BDNF) and dispensed onto the surface of the brain to provide sustained, local release of the protein using a procedure that avoids additional damage to neural tissue. The composite is simple to fabricate, and provides sustained release without nanoparticle encapsulation of BDNF, preserving material and protein bioactivity. We demonstrate that when delivered epicortically to a rat model of stroke, this composite allows BDNF to diffuse into the brain, resulting in enhanced behavioral recovery and synaptic plasticity in the contralesional hemisphere.

Initial cell maturity changes following transplantation in a hyaluronan-based hydrogel and impacts therapeutic success in the stroke-injured rodent brain.

Ischemic stroke results in a loss of neurons for which there are no available clinical strategies to stimulate regeneration. While preclinical studies have demonstrated that functional recovery can be obtained by transplanting an exogenous source of neural progenitors into the brain, it remains unknown at which stage of neuronal maturity cells will provide the most benefit. We investigated the role of neuronal maturity on cell survival, differentiation, and long-term sensorimotor recovery in stroke-injured rats using a population of human cortically-specified neuroepithelial progenitor cells (cNEPs) delivered in a biocompatible, bioresorbable hyaluronan/methylcellulose hydrogel.

Combined delivery of chondroitinase ABC and human induced pluripotent stem cell-derived neuroepithelial cells promote tissue repair in an animal model of spinal cord injury.

The lack of tissue regeneration after traumatic spinal cord injury in animal models is largely attributed to the local inhibitory microenvironment. To overcome this inhibitory environment while promoting tissue regeneration, we investigated the combined delivery of chondroitinase ABC (chABC) with human induced pluripotent stem cell-derived neuroepithelial stem cells (NESCs). ChABC was delivered to the injured spinal cord at the site of injury by affinity release from a crosslinked methylcellulose (MC) hydrogel by injection into the intrathecal space.

In Vitro Maturation of Human iPSC-Derived Neuroepithelial Cells Influences Transplant Survival in the Stroke-Injured Rat Brain.

Stem cell transplantation is a promising strategy for brain tissue regeneration; yet, despite some success, cell survival following transplantation remains low. In this study, we demonstrate that cell viability is enhanced by control over maturation of neuronal precursor cells, which are delivered in an injectable blend of hyaluronan and methylcellulose. We selected three subpopulations of human neuronal precursor cells derived from a cortically specified neuroepithelial stem cell (cNESC) population based on differences in expression of multipotent and neuron-specific proteins: early-, mid-, and late-differentiated neurons.

Blood vessel formation during tail regeneration in the leopard gecko (Eublepharis macularius): The blastema is not avascular.

Unique among amniotes, many lizards are able to self-detach (autotomize) their tail and then regenerate a replacement. Tail regeneration involves the formation of a blastema, an accumulation of proliferating cells at the site of autotomy. Over time, cells of the blastema give rise to most of the tissues in the replacement tail.

Delivery strategies for treatment of age-related ocular diseases: From a biological understanding to biomaterial solutions.

Age-related ocular diseases, such as age-related macular degeneration (AMD), diabetic retinopathy, and glaucoma, result in life-long functional deficits and enormous global health care costs. As the worldwide population ages, vision loss has become a major concern for both economic and human health reasons. Due to recent research into biomaterials and nanotechnology major advances have been gained in the field of ocular delivery.

The anatomy and histology of caudal autotomy and regeneration in lizards.

Abstract Caudal autotomy-the ability to self-detach the tail-is a dramatic adaptation common to many structural-grade lizards. For most species, tail loss is followed by the equally dramatic phenomenon of tail regeneration. Here we review the anatomy and histology of caudal autotomy and regeneration in lizards, drawing heavily from research published over the past 2 decades.

An osteological and histological investigation of cranial joints in geckos.

Cranial kinesis is a widespread feature of gekkotan lizards. Previous studies of kinesis in lizards often described the relevant, mobile joints as synovial, thus characterized by the presence of a synovial cavity lined with articular cartilage. To date however, detailed investigations of cranial joint histology are lacking.

In vitro studies on colonization resistance of the human gut microbiota to Candida albicans and the effects of tetracycline and Lactobacillus plantarum LPK.

An anaerobic three-vessel continuous-flow culture system, which models the three major anatomical regions of the human colon, was used to study the persistence of Candida albicans in the presence of a faecal microbiota. During steady state conditions, overgrowth of C. albicans was prevented by commensal bacteria indigenous to the system.