The role of elasticity on adhesion and clustering of neurons on soft surfaces.

The question of whether material stiffness enhances cell adhesion and clustering is still open to debate. Results from the literature are seemingly contradictory, with some reports illustrating that adhesion increases with surface stiffness and others suggesting that the performance of a system of cells is curbed by high values of elasticity. To address the role of elasticity as a regulator in neuronal cell adhesion and clustering, we investigated the topological characteristics of networks of neurons on polydimethylsiloxane (PDMS) surfaces - with values of elasticity (E) varying in the 0.

One-Step Precise Characterization of Drug Delivery Systems by PULCON Magnetic Resonance Spectroscopy.

Polymers are extensively used for the realization of drug delivery systems across multiple scales, from nanomedicines to microparticles and macroscopic implantable devices, for their favorable biodegradation profiles and tunable physicochemical features. The accurate quantification of the polymer content is key to finely controlling drug loading and release and ensuring reproducibility, yet it continues to be a major challenge in the design and development of delivery systems. In this study, we introduce a novel protocol based on the PULCON technique to quantify, with a routine NMR spectroscopy analysis, the precise concentration of polymers in various delivery systems.

μMESH-Enabled Sustained Delivery of Molecular and Nanoformulated Drugs for Glioblastoma Treatment.

Modest tissue penetrance, nonuniform distribution, and suboptimal release of drugs limit the potential of intracranial therapies against glioblastoma. Here, a conformable polymeric implant, μMESH, is realized by intercalating a micronetwork of 3 × 5 μm poly(lactic--glycolic acid) (PLGA) edges over arrays of 20 × 20 μm polyvinyl alcohol (PVA) pillars for the sustained delivery of potent chemotherapeutic molecules, docetaxel (DTXL) and paclitaxel (PTXL). Four different μMESH configurations were engineered by encapsulating DTXL or PTXL within the PLGA micronetwork and nanoformulated DTXL (nanoDTXL) or PTXL (nanoPTXL) within the PVA microlayer.

Microstructured Polymeric Fabrics Modulating the Paracrine Activity of Adipose-Derived Stem Cells.

The deposition of stem cells at sites of injury is a clinically relevant approach to facilitate tissue repair and angiogenesis. However, insufficient cell engraftment and survival require the engineering of novel scaffolds. Here, a regular network of microscopic poly(lactic-co-glycolic acid) (PLGA) filaments was investigated as a promising biodegradable scaffold for human Adipose-Derived Stem Cell (hADSC) tissue integration.

Boosting the Potential of Chemotherapy in Advanced Breast Cancer Lung Metastasis via Micro-Combinatorial Hydrogel Particles.

Breast cancer cell colonization of the lungs is associated with a dismal prognosis as the distributed nature of the disease and poor permeability of the metastatic foci challenge the therapeutic efficacy of small molecules, antibodies, and nanomedicines. Taking advantage of the unique physiology of the pulmonary circulation, here, micro-combinatorial hydrogel particles (µCGP) are realized via soft lithographic techniques to enhance the specific delivery of a cocktail of cytotoxic nanoparticles to metastatic foci. By cross-linking short poly(ethylene glycol) (PEG) chains with erodible linkers within a shape-defining template, a deformable and biodegradable polymeric skeleton is realized and loaded with a variety of therapeutic and imaging agents, including docetaxel-nanoparticles.

Investigating the impacts of HO treatment on gills of healthy Atlantic salmon reveals potential changes to mucus production with implications on immune activity.

Current treatment strategies for relevant infectious diseases in Atlantic salmon (Salmo salar L.) include the use of low salinity or freshwater bathing. However, often availability is restricted, and hydrogen peroxide (HO) is used as an alternative.

Boosting the therapeutic efficacy of discoidal nanoconstructs against glioblastoma with rationally designed PEG-Docetaxel conjugates.

Maximizing loading while modulating the release of therapeutic molecules from nanoparticles and implantable drug delivery systems is the key to successfully address deadly diseases like brain cancer. Here, four different conjugates of the potent chemotherapeutic molecule docetaxel (DTXL)were realized to optimize the pharmacological properties of 1,000 × 400 nmDiscoidal PolymericNanoconstructs(DPNs). DTXL was covalently linked to poly-(ethylene) glycol(PEG)chains of different molecular weights, namely 350, 550 and 1,000 Da, and oleic acid (OA).

Shape-specific microfabricated particles for biomedical applications: a review.

The storied history of controlled the release systems has evolved over time; from degradable drug-loaded sutures to monolithic zero-ordered release devices and nano-sized drug delivery formulations. Scientists have tuned the physico-chemical properties of these drug carriers to optimize their performance in biomedical/pharmaceutical applications. In particular, particle drug delivery systems at the micron size regime have been used since the 1980s.

Insulin Granule-Loaded MicroPlates for Modulating Blood Glucose Levels in Type-1 Diabetes.

Type-1 diabetes (T1DM) is a chronic metabolic disorder resulting from the autoimmune destruction of β cells. The current standard of care requires multiple, daily injections of insulin and accurate monitoring of blood glucose levels (BGLs); in some cases, this results in diminished patient compliance and increased risk of hypoglycemia. Herein, we engineered hierarchically structured particles comprising a poly(lactic--glycolic) acid (PLGA) prismatic matrix, with a 20 × 20 μm base, encapsulating 200 nm insulin granules.

Shape-Defined microPlates for the Sustained Intra-articular Release of Dexamethasone in the Management of Overload-Induced Osteoarthritis.

Osteoarthritis (OA) is treated with the intra-articular injection of steroids such as dexamethasone (DEX) to provide short-term pain management. However, DEX treatment suffers from rapid joint clearance. Here, 20 × 10 μm, shape-defined poly(d,l-lactide-co-glycolide)acid microPlates (μPLs) are created and intra-articularly deposited for the sustained release of DEX.

Conformable hierarchically engineered polymeric micromeshes enabling combinatorial therapies in brain tumours.

The poor transport of molecular and nanoscale agents through the blood-brain barrier together with tumour heterogeneity contribute to the dismal prognosis in patients with glioblastoma multiforme. Here, a biodegradable implant (μMESH) is engineered in the form of a micrometre-sized poly(lactic-co-glycolic acid) mesh laid over a water-soluble poly(vinyl alcohol) layer. Upon poly(vinyl alcohol) dissolution, the flexible poly(lactic-co-glycolic acid) mesh conforms to the resected tumour cavity as docetaxel-loaded nanomedicines and diclofenac molecules are continuously and directly released into the adjacent tumour bed.

Enhancing islet transplantation using a biocompatible collagen-PDMS bioscaffold enriched with dexamethasone-microplates.

Islet transplantation is a promising approach to enable type 1 diabetic patients to attain glycemic control independent of insulin injections. However, up to 60% of islets are lost immediately following transplantation. To improve this outcome, islets can be transplanted within bioscaffolds, however, synthetic bioscaffolds induce an intense inflammatory reaction which can have detrimental effects on islet function and survival.

Roadmap on nanomedicine.

Since the launch of the Alliance for Nanotechnology in Cancer by the National Cancer Institute in late 2004, several similar initiatives have been promoted all over the globe with the intention of advancing the diagnosis, treatment and prevention of cancer in the wake of nanoscience and nanotechnology. All this has encouraged scientists with diverse backgrounds to team up with one another, learn from each other, and generate new knowledge at the interface between engineering, physics, chemistry and biomedical sciences. Importantly, this new knowledge has been wisely channeled towards the development of novel diagnostic, imaging and therapeutic nanosystems, many of which are currently at different stages of clinical development.

Drug delivery: Experiments, mathematical modelling and machine learning.

We address the problem of determining from laboratory experiments the data necessary for a proper modeling of drug delivery and efficacy in anticancer therapy. There is an inherent difficulty in extracting the necessary parameters, because the experiments often yield an insufficient quantity of information. To overcome this difficulty, we propose to combine real experiments, numerical simulation, and Machine Learning (ML) based on Artificial Neural Networks (ANN), aiming at a reliable identification of the physical model factors, e.

Nanoformulated Zoledronic Acid Boosts the Vδ2 T Cell Immunotherapeutic Potential in Colorectal Cancer.

Aminobisphosphonates, such as zoledronic acid (ZA), have shown potential in the treatment of different malignancies, including colorectal carcinoma (CRC). Yet, their clinical exploitation is limited by their high bone affinity and modest bioavailability. Here, ZA is encapsulated into the aqueous core of spherical polymeric nanoparticles (SPNs), whose size and architecture resemble that of biological vesicles.

Engineering shape-defined PLGA microPlates for the sustained release of anti-inflammatory molecules.

Over the years, nanoparticles, microparticles, implants of poly(D,l-lactide-co-glycolide) (PLGA) have been demonstrated for diverse biomedical applications. Yet, initial burst release and optimal modulation of the release profiles limit their clinical use. Here, shape-defined PLGA microPlates (μPLs) were realized for the sustained release of two anti-inflammatory molecules, the natural polyphenol curcumin (CURC) and the corticosteroid dexamethasone (DEX).

Quantitative micro-Raman analysis of micro-particles in drug delivery.

Polymeric micro and nanoconstructs are emerging as promising delivery systems for therapeutics and contrast agents in microcirculation. Excellent assets associated with polymeric particulates of tunable shape, size, mechanical and chemical properties may improve the efficiency of delivery and represent the basis of personalized medicine and treatment. Nevertheless, lack of effective techniques of analysis may limit their use in biomedicine and bioengineering.

A new strategy based on microwave-assisted technology for the extraction and purification of beeswax policosanols for pharmaceutical purposes and beyond.

Policosanols (PCs) are a mixture of long chain primary aliphatic alcohols mainly known for their ability to reduce cholesterol level. Due to this property, there is an increasing interest in the extraction process of these compounds. In this context, beeswax, a natural product produced by honey bees of the genus Apis, is a promising source for their extraction and purification.

Methacarn preserves mucus integrity and improves visualization of amoebae in gills of Atlantic salmon (Salmo salar L.).

Two aqueous fixation methods (modified Davidson's solution and modified Davidson's solution with 2% (w/v) Alcian blue) were compared against two non-aqueous fixation methods (methacarn solution and methacarn solution with 2% (w/v) Alcian blue) along with the standard buffered formalin fixation method to (a) improve preservation of the mucous coat on Atlantic salmon, Salmo salar L., gills and (b) to examine the interaction between the amoebae and mucus on the gill during an infection with amoebic gill disease. Aqueous fixatives demonstrated excellent cytological preservation but failed to deliver the preservation of the mucus when compared to the non-aqueous-based fixatives; qualitative and semi-quantitative analysis revealed a greater preservation of the gill mucus using the non-aqueous methacarn solution.

Hierarchical Microplates as Drug Depots with Controlled Geometry, Rigidity, and Therapeutic Efficacy.

A variety of microparticles have been proposed for the sustained and localized delivery of drugs with the objective of increasing therapeutic indexes by circumventing filtering organs and biological barriers. Yet, the geometrical, mechanical, and therapeutic properties of such microparticles cannot be simultaneously and independently tailored during the fabrication process to optimize their performance. In this work, a top-down approach is employed to realize micron-sized polymeric particles, called microplates (μPLs), for the sustained release of therapeutic agents.

Ameliorating Amyloid-β Fibrils Triggered Inflammation Curcumin-Loaded Polymeric Nanoconstructs.

Inflammation is a common hallmark in several diseases, including atherosclerosis, cancer, obesity, and neurodegeneration. In Alzheimer's disease (AD), growing evidence directly correlates neuronal damage with inflammation of myeloid brain cells, such as microglia. Here, polymeric nanoparticles were engineered and characterized for the delivery of anti-inflammatory molecules to macrophages stimulated via direct incubation with amyloid-β fibers.

Spherical polymeric nanoconstructs for combined chemotherapeutic and anti-inflammatory therapies.

Nanoparticles can simultaneously deliver multiple agents to cancerous lesions enabling de facto combination therapies. Here, spherical polymeric nanoconstructs (SPNs) are loaded with anti-cancer - docetaxel (DTXL) - and anti-inflammatory - diclofenac (DICL) - molecules. In vitro, combination SPNs kill U87-MG cells twice as efficiently as DTXL SPNs, achieving a IC of 90.

Soft Discoidal Polymeric Nanoconstructs Resist Macrophage Uptake and Enhance Vascular Targeting in Tumors.

Most nanoparticles for biomedical applications originate from the self-assembling of individual constituents through molecular interactions and possess limited geometry control and stability. Here, 1000 × 400 nm discoidal polymeric nanoconstructs (DPNs) are demonstrated by mixing hydrophobic and hydrophilic polymers with lipid chains and curing the resulting paste directly within silicon templates. By changing the paste composition, soft- and rigid-DPNs (s- and r-DPNs) are synthesized exhibiting the same geometry, a moderately negative surface electrostatic charge (-14 mV), and different mechanical stiffness (∼1.