DetectEV: A functional enzymatic assay to assess integrity and bioactivity of extracellular vesicles.

The application of extracellular vesicles (EVs) as therapeutics or nanocarriers in cell-free therapies necessitates meticulous evaluations of different features, including their identity, bioactivity, batch-to-batch reproducibility, and stability. Given the inherent heterogeneity in EV preparations, this assessment demands sensitive functional assays to provide key quality control metrics, complementing established methods to ensure that EV preparations meet the required functionality and quality standards. Here, we introduce the detectEV assay, an enzymatic-based approach for assessing EV luminal cargo bioactivity and membrane integrity.

The Multifaced Role of Collagen in Cancer Development and Progression.

Collagen is a crucial protein in the extracellular matrix (ECM) essential for preserving tissue architecture and supporting crucial cellular functions like proliferation and differentiation. There are twenty-eight identified types of collagen, which are further divided into different subgroups. This protein plays a critical role in regulating tissue homeostasis.

Nucleic Acids-Based Biomarkers for Alzheimer's Disease Diagnosis and Novel Molecules to Treat the Disease.

Alzheimer's disease (AD) represents the most common form of dementia and affects million people worldwide, with a high social burden and considerable economic costs. AD diagnosis benefits from a well-established panel of laboratory tests that allow ruling-in patients, along with FDG and amyloid PET imaging tools. The main laboratory tests used to identify AD patients are Aβ40, Aβ42, the Aβ42/Aβ40 ratio, phosphorylated Tau 181 (pTau181) and total Tau (tTau).

Effects of Cerebrospinal Fluids from Alzheimer and Non-Alzheimer Patients on Neurons-Astrocytes-Microglia Co-Culture.

Alzheimer's disease (AD) is the most common form of dementia, characterized by the accumulation of β-amyloid plaques, tau tangles, neuroinflammation, and synaptic/neuronal loss, the latter being the strongest correlating factor with memory and cognitive impairment. Through an in vitro study on a neurons-astrocytes-microglia (NAM) co-culture system, we analyzed the effects of cerebrospinal fluid (CSF) samples from AD and non-AD patients (other neurodegenerative pathologies). Treatment with CSF from AD patients showed a loss of neurofilaments and spheroids, suggesting the presence of elements including CX3CL1 (soluble form), destabilizing the neurofilaments, cellular adhesion processes, and intercellular contacts.

Collagen-Based Scaffolds for Chronic Skin Wound Treatment.

Chronic wounds, commonly known as ulcers, represent a significant challenge to public health, impacting millions of individuals every year and imposing a significant financial burden on the global health system. Chronic wounds result from the interruption of the natural wound-healing process due to internal and/or external factors, resulting in slow or nonexistent recovery. Conventional medical approaches are often inadequate to deal with chronic wounds, necessitating the exploration of new methods to facilitate rapid and effective healing.

Cerebrospinal and Blood Biomarkers in Alzheimer's Disease: Did Mild Cognitive Impairment Definition Affect Their Clinical Usefulness?

Despite Alzheimer's Disease (AD) being known from the times of Alois Alzheimer, who lived more than one century ago, many aspects of the disease are still obscure, including the pathogenesis, the clinical spectrum definition, and the therapeutic approach. Well-established biomarkers for AD come from the histopathological hallmarks of the disease, which are Aβ and phosphorylated Tau protein aggregates. Consistently, cerebrospinal fluid (CSF) Amyloid β (Aβ) and phosphorylated Tau level measurements are currently used to detect AD presence.

Mimicking Molecular Pathways in the Design of Smart Hydrogels for the Design of Vascularized Engineered Tissues.

Biomaterials are pivotal in supporting and guiding vascularization for therapeutic applications. To design effective, bioactive biomaterials, understanding the cellular and molecular processes involved in angiogenesis and vasculogenesis is crucial. Biomaterial platforms can replicate the interactions between cells, the ECM, and the signaling molecules that trigger blood vessel formation.

Monitoring the macrophage response towards biomaterial implants using label-free imaging.

Understanding the immune system's foreign body response (FBR) is essential when developing and validating a biomaterial. Macrophage activation and proliferation are critical events in FBR that can determine the material's biocompatibility and fate in vivo. In this study, two different macro-encapsulation pouches intended for pancreatic islet transplantation were implanted into streptozotocin-induced diabetes rat models for 15 days.

CX3CL1 Pathway as a Molecular Target for Treatment Strategies in Alzheimer's Disease.

Alzheimer's disease (AD) is a scourge for patients, caregivers and healthcare professionals due to the progressive character of the disease and the lack of effective treatments. AD is considered a proteinopathy, which means that aetiological and clinical features of AD have been linked to the deposition of amyloid β (Aβ) and hyperphosphorylated tau protein aggregates throughout the brain, with Aβ and hyperphosphorylated tau representing classical AD hallmarks. However, some other putative mechanisms underlying the pathogenesis of the disease have been proposed, including inflammation in the brain, microglia activation, impaired hippocampus neurogenesis and alterations in the production and release of neurotrophic factors.

The Cytokine CX3CL1 and ADAMs/MMPs in Concerted Cross-Talk Influencing Neurodegenerative Diseases.

Neuroinflammation plays a fundamental role in the development and progression of neurodegenerative diseases. It could therefore be said that neuroinflammation in neurodegenerative pathologies is not a consequence but a cause of them and could represent a therapeutic target of neuronal degeneration. CX3CL1 and several proteases (ADAMs/MMPs) are strongly involved in the inflammatory pathways of these neurodegenerative pathologies with multiple effects.

Recovery of Bioactive Compounds from Marine Organisms: Focus on the Future Perspectives for Pharmacological, Biomedical and Regenerative Medicine Applications of Marine Collagen.

Marine environments cover more than 70% of the Earth's surface and are among the richest and most complex ecosystems. In terms of biodiversity, the ocean represents an important source, still not widely exploited, of bioactive products derived from species of bacteria, plants, and animals. However, global warming, in combination with multiple anthropogenic practices, represents a serious environmental problem that has led to an increase in gelatinous zooplankton, a phenomenon referred to as jellyfish bloom.

Microglial Activation and Priming in Alzheimer's Disease: State of the Art and Future Perspectives.

Alzheimer's Disease (AD) is the most common cause of dementia, having a remarkable social and healthcare burden worldwide. Amyloid β (Aβ) and protein Tau aggregates are disease hallmarks and key players in AD pathogenesis. However, it has been hypothesized that microglia can contribute to AD pathophysiology, as well.

High Cerebrospinal Fluid CX3CL1 Levels in Alzheimer's Disease Patients but Not in Non-Alzheimer's Disease Dementia.

Alzheimer's disease (AD) is the most common form of cognitive decline worldwide, occurring in about 10% of people older than 65 years. The well-known hallmarks of AD are extracellular aggregates of amyloid β (Aβ) and intracellular neurofibrillary tangles (NFTs) of tau protein. The evidence that Aβ overproduction leads to AD has paved the way for the AD pathogenesis amyloid cascade hypothesis, which proposes that the neuronal damage is sustained by Aβ overproduction.

Continuous Microfiber Wire Mandrel-Less Biofabrication for Soft Tissue Engineering Applications.

Suture materials are the most common bioimplants in surgical and clinical practice, playing a crucial role in wound healing and tendon and ligament repair. Despite the assortment available on the market, sutures are still affected by significant disadvantages, including failure in mimicking the mechanical properties of the tissue, excessive fibrosis, and inflammation. This study introduces a mandrel-less electrodeposition apparatus to fabricate continuous microfiber wires of indefinite length.

Assessing the Effects of VEGF Releasing Microspheres on the Angiogenic and Foreign Body Response to a 3D Printed Silicone-Based Macroencapsulation Device.

Macroencapsulation systems have been developed to improve islet cell transplantation but can induce a foreign body response (FBR). The development of neovascularization adjacent to the device is vital for the survival of encapsulated islets and is a limitation for long-term device success. Previously we developed additive manufactured multi-scale porosity implants, which demonstrated a 2.

Functionalized Poly(-isopropylacrylamide)-Based Microgels in Tumor Targeting and Drug Delivery.

Over the past several decades, the development of engineered small particles as targeted and drug delivery systems (TDDS) has received great attention thanks to the possibility to overcome the limitations of classical cancer chemotherapy, including targeting incapability, nonspecific action and, consequently, systemic toxicity. Thus, this research aims at using a novel design of Poly(-isopropylacrylamide) p(NIPAM)-based microgels to specifically target cancer cells and avoid the healthy ones, which is expected to decrease or eliminate the side effects of chemotherapeutic drugs. Smart NIPAM-based microgels were functionalized with acrylic acid and coupled to folic acid (FA), targeting the folate receptors overexpressed by cancer cells and to the chemotherapeutic drug doxorubicin (Dox).

The Foreign Body Response to an Implantable Therapeutic Reservoir in a Diabetic Rodent Model.

Advancements in type 1 diabetes mellitus treatments have vastly improved in recent years. The move toward a bioartificial pancreas and other fully implantable systems could help restore patient's glycemic control. However, the long-term success of implantable medical devices is often hindered by the foreign body response.

Core-shell PLA/Kef hybrid scaffolds for skin tissue engineering applications prepared by direct kefiran coating on PLA electrospun fibers optimized via air-plasma treatment.

Over the recent years, there is a growing interest in electrospun hybrid scaffolds composed of synthetic and natural polymers that can support cell attachment and proliferation. In this work, the physical and biological properties of polylactic acid (PLA) electrospun mats coated with kefiran (Kef) were evaluated. Gravimetric, spectroscopic (FTIR-ATR) and morphological investigations via scanning electron microscopy confirmed the effective formation of a thin kefiran layer wrapped on the PLA fibers with an easy-tunable thickness.

3D Collagen Hydrogel Promotes In Vitro Langerhans Islets Vascularization through ad-MVFs Angiogenic Activity.

Adipose derived microvascular fragments (ad-MVFs) consist of effective vascularization units able to reassemble into efficient microvascular networks. Because of their content in stem cells and related angiogenic activity, ad-MVFs represent an interesting tool for applications in regenerative medicine. Here we show that gentle dissociation of rat adipose tissue provides a mixture of ad-MVFs with a length distribution ranging from 33-955 μm that are able to maintain their original morphology.

Additive Manufacturing of Multi-Scale Porous Soft Tissue Implants That Encourage Vascularization and Tissue Ingrowth.

Medical devices, such as silicone-based prostheses designed for soft tissue implantation, often induce a suboptimal foreign-body response which results in a hardened avascular fibrotic capsule around the device, often leading to patient discomfort or implant failure. Here, it is proposed that additive manufacturing techniques can be used to deposit durable coatings with multiscale porosity on soft tissue implant surfaces to promote optimal tissue integration. Specifically, the "liquid rope coil effect", is exploited via direct ink writing, to create a controlled macro open-pore architecture, including over highly curved surfaces, while adapting atomizing spray deposition of a silicone ink to create a microporous texture.

Physical and biological properties of electrospun poly(d,l-lactide)/nanoclay and poly(d,l-lactide)/nanosilica nanofibrous scaffold for bone tissue engineering.

Electrospun scaffolds exhibiting high physical performances with the ability to support cell attachment and proliferation are attracting more and more scientific interest for tissue engineering applications. The inclusion of inorganic nanoparticles such as nanosilica and nanoclay into electrospun biopolymeric matrices can meet these challenging requirements. The silica and clay incorporation into polymeric nanofibers has been reported to enhance and improve the mechanical properties as well as the osteogenic properties of the scaffolds.

Tuning of the Mg Alloy AZ31 Anodizing Process for Biodegradable Implants.

Coatings were grown on the AZ31 Mg alloy by a hard anodizing process in the hot glycerol phosphate-containing electrolyte. Anodizing conditions were optimized, maximizing corrosion resistance estimated by impedance measurements carried out in Hank's solution at 37 °C. A post anodizing annealing treatment (350 °C for 24 h) allowed us to further enhance the corrosion resistance of the coatings mainly containing magnesium phosphate according to energy-dispersive X-ray spectroscopy and Raman analyses.

Production of Injectable Marine Collagen-Based Hydrogel for the Maintenance of Differentiated Chondrocytes in Tissue Engineering Applications.

Cartilage is an avascular tissue with limited ability of self-repair. The use of autologous chondrocyte transplants represent an effective strategy for cell regeneration; however, preserving the differentiated state, which ensures the ability to regenerate damaged cartilage, represents the main challenge during culturing. For this purpose, we produced an injectable marine collagen-based hydrogel, by mixing native collagen from the jellyfish with hydroxy-phenyl-propionic acid (HPA)-functionalized marine gelatin.