Electrically Conductive Injectable Silk/PEDOT: PSS Hydrogel for Enhanced Neural Network Formation.

With no effective treatments for functional recovery after injury, spinal cord injury (SCI) remains one of the unresolved healthcare challenges. Human induced pluripotent stem cell (hiPSC) transplantation is a versatile patient-specific regenerative approach for functional recovery after SCI. Injectable electroconductive hydrogel (ECH) can further enhance the cell transplantation efficacy through a minimally invasive manner as well as recapitulate the native bioelectrical microenvironment of neural tissue.

Association between Driving Pressure, Systemic Inflammation and Non-pulmonary Organ Dysfunction in Patients with Acute Respiratory Distress Syndrome, a Prospective Pathophysiological Study.

Background: Driving pressure is thought to determine the effect of low tidal ventilation on survival in patients with acute respiratory distress syndrome. The leading cause of mortality in these patients is non-pulmonary multiorgan dysfunction, which is believed to worsen due to the biological response to mechanical ventilation (biotrauma). Therefore, we aimed to analyze the association between driving pressure, biotrauma, and non-pulmonary multiorgan dysfunction.

Healing the Cornea: Exploring the Therapeutic Solutions Offered by MSCs and MSC-derived EVs.

Affecting a large proportion of the population worldwide, corneal disorders constitute a concerning health hazard associated to compromised eyesight or blindness for most severe cases. In the last decades, mesenchymal stem/stromal cells (MSCs) demonstrated promising abilities in improving symptoms associated to corneal diseases or alleviating these affections, especially through their anti-inflammatory, immunomodulatory and pro-regenerative properties. More recently, MSC therapeutic potential was shown to be mediated by the molecules they release, and particularly by their extracellular vesicles (EVs; MSC-EVs).

Development and Characterization of 3-Dimensional Cell Culture Models of Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex that is associated with a poor prognosis. Developing effective treatment options for ACC is challenging owing to the current lack of representative preclinical models. This study addressed this limitation by developing and characterizing 3-dimensional (3D) cell cultures incorporating the ACC cell lines, MUC-1, HAC15, and H295R in a type I collagen matrix.

The Comprehensive Resilience-building psychosocial Intervention (CREST) for people with dementia in the community: a feasibility and acceptability study.

Background: A dementia diagnosis can lead to a decline in cognitive, social, and physical health, but people with dementia can live meaningful lives and participate actively in society with psychosocial support. This single-arm, non-randomised feasibility study explored the feasibility and acceptability of a Comprehensive REsilience-building psychoSocial intervenTion (CREST) for people with dementia, their caregivers, General Practitioners (GPs), and the public.

Methods: Nine people with dementia and their primary caregivers living in the community (n = 9 dyads) completed the CREST intervention which had three components (cognitive stimulation therapy [CST], physical exercise, and dementia education).

Shear-Thinning Extrudable Hydrogels Based on Star Polypeptides with Antimicrobial Properties.

Hydrogels with low toxicity, antimicrobial potency and shear-thinning behavior are promising materials to combat the modern challenges of increased infections. Here, we report on 8-arm star block copolypeptides based on poly(L-lysine), poly(L-tyrosine) and poly(S-benzyl-L-cysteine) blocks. Three star block copolypeptides were synthesized with poly(S-benzyl-L-cysteine) always forming the outer block.

Tumor-associated mesenchymal stromal cells modulate macrophage phagocytosis in stromal-rich colorectal cancer via PD-1 signaling.

CMS4 colorectal cancer (CRC), based on the consensus molecular subtype (CMS), stratifies patients with the poorest disease-free survival rates. It is characterized by a strong mesenchymal stromal cell (MSC) signature, wound healing-like inflammation and therapy resistance. We utilized 2D and 3D , and models to assess the impact of inflammation and stromal cells on immunosuppression in CMS4 CRC.

Digital Light Processing of Thermoresponsive Hydrogels from Polyproline-Based Star Polypeptides.

The first report of star poly(L-proline) crosslinkers is disclosed for digital light processing 3D printing of thermoresponsive hydrogels. Through chain end functionalization of star poly(L-proline)s with methacryloyl groups, access to high-resolution defined 3D hydrogel structures via digital light processing is achieved through photoinitiated free radical polymerization. Changing the poly(L-proline) molecular weight has a direct influence on both thermoresponsiveness and printability, while shape-morphing behavior can be induced thermally.

Immunomodulatory potential of cytokine-licensed human bone marrow-derived mesenchymal stromal cells correlates with potency marker expression profile.

Cytokine(s) pre-activation/licensing is an effective way to enhance the immunomodulatory potency of mesenchymal stromal cells (MSCs). Currently, IFN-γ licensing received the most attention in comparison with other cytokines. After licensing human bone marrow-derived MSCs with pro-/anti-inflammatory cytokines IFN-γ, IL-1β, TNF-α, TGF-β1 alone or in combination, the in vitro immunomodulatory potency of these MSCs was studied by incubating with allogeneic T cells and macrophage-like THP-1 cells.

NK cell line modified to express a potent, DR5 specific variant of TRAIL, show enhanced cytotoxicity in ovarian cancer models.

Objective: Ovarian cancer is a lethal gynaecological malignancy with unsatisfactory 5 year survival rates of 30-50 %. Cell immunotherapy is a promising new cancer treatment where immune cells, such as Natural Killer (NK) cells, are administered to enable the patient to fight cancer through direct cytotoxicity. NK cells orchestrate an adaptive immune response by enabling the release of tumour antigens.

Mining human clinical waste as a rich source of stem cells for neural regeneration.

Neural diseases are challenging to treat and are regarded as one of the major causes of disability and morbidity in the world. Stem cells can provide a solution, by offering a mechanism to replace damaged circuitry. However, obtaining sufficient cell sources for neural regeneration remains a significant challenge.

A functional analysis of a resorbable citrate-based composite tendon anchor.

Rapid and efficient tendon fixation to a bone following trauma or in response to degenerative processes can be facilitated using a tendon anchoring device. Osteomimetic biomaterials, and in particular, bio-resorbable polymer composites designed to match the mineral phase content of native bone, have been shown to exhibit osteoinductive and osteoconductive properties and have been used in bone fixation for the past 2 decades. In this study, a resorbable, bioactive, and mechanically robust citrate-based composite formulated from poly(octamethylene citrate) (POC) and hydroxyapatite (HA) (POC-HA) was investigated as a potential tendon-fixation biomaterial.

There Is No Direct Causal Relationship Between Coronary Artery Disease and Alzheimer Disease: A Bidirectional Mendelian Randomization Study.

Background: The association between poor cardiovascular health and cognitive decline as well as dementia progression has been inconsistent across studies. This study used Mendelian randomization (MR) to investigate the causal relationship between Alzheimer disease (AD), circulating levels of total-tau, and coronary artery disease (CAD).

Methods And Results: This study used MR to investigate the causal relationship between AD or circulating levels of total-tau and CAD, including ischemic heart disease, myocardial infarction, coronary heart disease, coronary atherosclerosis, and heart failure.

Poly(l-proline)-Stabilized Polypeptide Nanostructures via Ring-Opening Polymerization-Induced Self-Assembly (ROPISA).

Poly(proline) II helical motifs located at the protein-water interface stabilize the three-dimensional structures of natural proteins. Reported here is the first example of synthetic biomimetic poly(proline)-stabilized polypeptide nanostructures obtained by a straightforward ring-opening polymerization-induced self-assembly (ROPISA) process through consecutive -carboxyanhydride (NCA) polymerization. It was found that the use of multifunctional 8-arm initiators is critical for the formation of nanoparticles.

Extracellular matrix-inspired biomaterials for wound healing.

Diabetic foot ulcers (DFU) are a debilitating and life-threatening complication of Diabetes Mellitus. Ulceration develops from a combination of associated diabetic complications, including neuropathy, circulatory dysfunction, and repetitive trauma, and they affect approximately 19-34% of patients as a result. The severity and chronic nature of diabetic foot ulcers stems from the disruption to normal wound healing, as a result of the molecular mechanisms which underly diabetic pathophysiology.

Transcriptomic and proteomic profiling of bi-partite and tri-partite murine iPSC-derived neurospheroids under steady-state and inflammatory condition.

induced-pluripotent stem cell (iPSC)-derived neurospheroid (NSPH) models are an emerging in vitro toolkit to study the influence of inflammatory triggers on neurodegeneration and repair in a 3D neural environment. In contrast to their human counterpart, the absence of murine iPSC-derived NSPHs for profound characterisation and validation studies is a major experimental research gap, even though they offer the only possibility to truly compare or validate in vitro NSPH responses with in vivo brain responses. To contribute to these developments, we here describe the generation and characterisation of 5-week-old CXCR1 CCR2 murine (m)iPSC-derived bi-partite (neurons + astrocytes) and tri-partite (neurons + astrocytes + microglia) NSPH models that can be subjected to cellular activation following pro-inflammatory stimulation.

An exploratory randomised trial investigating feasibility, potential impact and cost effectiveness of link workers for people living with multimorbidity attending general practices in deprived urban communities.

Background: Social prescribing link workers are non-health or social care professionals who connect people with psychosocial needs to non-clinical community supports. They are being implemented widely, but there is limited evidence for appropriate target populations or cost effectiveness. This study aimed to explore the feasibility, potential impact on health outcomes and cost effectiveness of practice-based link workers for people with multimorbidity living in deprived urban communities.

Melt electrowriting of poly(-caprolactone)-poly(ethylene glycol) backbone polymer blend scaffolds with improved hydrophilicity and functionality.

Melt electrowriting (MEW) is an additive manufacturing technique that harnesses electro-hydrodynamic phenomena to produce 3D-printed fibres with diameters on the scale of 10s of microns. The ability to print at this small scale provides opportunities to create structures with incredibly fine resolution and highly defined morphology. The current gold standard material for MEW is poly(ϵ-caprolactone) (PCL), a polymer with excellent biocompatibility but lacking in chemical groups that can allow intrinsic additional functionality.

Move for Life an intervention for inactive adults aged 50 years and older: a cluster randomised feasibility trial.

Background: Move for Life (MFL) is a theory-informed intervention that was developed to augment established physical activity (PA) programmes and enable inactive adults aged 50 years and older to be more active. This study examined the feasibility of MFL and sought to provide evidence of its potential for improving PA and associated health outcomes.

Methods: A 3-arm cluster randomised feasibility trial compared MFL intervention, usual provision (UP) and control (CON) groups at baseline (T0), post-intervention (T1, at 8, 10 or 12- weeks) and 6-month follow up (T2).

Outcomes after reversed corneal graft rejection: a report from the European VISICORT project.

Objective: This study aims to describe the outcome of corneal grafts, both low risk and high risk, after successfully reversed immunological rejection.

Methods: Datasets on reversed rejection episodes in penetrating and endothelial keratoplasties between 2014 and 2019 (n=876) were extracted from the Adverse Immune Signatures and their Prevention in Corneal Transplantation database, which contains the prospectively and consecutively collected corneal transplants from five European centres. Stratified by the preoperatively determined risk status for immunological rejection, the outcome parameters analysed included visual acuity, intraocular pressure, endothelial cell density and central corneal thickness before and after reversed rejection episodes.

Exploring therapy transport from implantable medical devices using experimentally informed computational methods.

Implantable medical devices that can facilitate therapy transport to localized sites are being developed for a number of diverse applications, including the treatment of diseases such as diabetes and cancer, and tissue regeneration after myocardial infraction. These implants can take the form of an encapsulation device which encases therapy in the form of drugs, proteins, cells, and bioactive agents, in semi-permeable membranes. Such implants have shown some success but the nature of these devices pose a barrier to the diffusion of vital factors, which is further exacerbated upon implantation due to the foreign body response (FBR).

Gums as Macromolecular Crowding Agents in Human Skin Fibroblast Cultures.

Even though tissue-engineered medicines are under intense academic, clinical, and commercial investigation, only a handful of products have been commercialised, primarily due to the costs associated with their prolonged manufacturing. While macromolecular crowding has been shown to enhance and accelerate extracellular matrix deposition in eukaryotic cell culture, possibly offering a solution in this procrastinating tissue-engineered medicine development, there is still no widely accepted macromolecular crowding agent. With these in mind, we herein assessed the potential of gum Arabic, gum gellan, gum karaya, and gum xanthan as macromolecular crowding agents in WS1 skin fibroblast cultures (no macromolecular crowding and carrageenan were used as a control).

Clinical potential of plasma-functionalized graphene oxide ultrathin sheets for bone and blood vessel regeneration: Insights from cellular and animal models.

Graphene and graphene oxide (GO), due to their unique chemical and physical properties, possess biochemical characteristics that can trigger intercellular signals promoting tissue regeneration. Clinical applications of thin GO-derived sheets have inspired the development of various tissue regeneration and repair approaches. In this study, we demonstrate that ultrathin sheets of plasma-functionalized and reduced GO, with the oxygen content ranging from 3.