Assessment of spinal cord injury using ultrasound elastography in a rabbit model in vivo.

The effect of the mechanical micro-environment on spinal cord injury (SCI) and treatment effectiveness remains unclear. Currently, there are limited imaging methods that can directly assess the localized mechanical behavior of spinal cords in vivo. In this study, we apply new ultrasound elastography (USE) techniques to assess SCI in vivo at the site of the injury and at the time of one week post injury, in a rabbit animal model.

Immunomodulatory biomimetic nanoparticles target articular cartilage trauma after systemic administration.

Post-traumatic osteoarthritis (PTOA) is one of the leading causes of disability in developed countries and accounts for 12% of all osteoarthritis cases in the United States. After trauma, inflammatory cells (macrophages amongst others) are quickly recruited within the inflamed synovium and infiltrate the joint space, initiating dysregulation of cartilage tissue homeostasis. Current therapeutic strategies are ineffective, and PTOA remains an open clinical challenge.

LDL-Based Lipid Nanoparticle Derived for Blood Plasma Accumulates Preferentially in Atherosclerotic Plaque.

Apolipoprotein-based drug delivery is a promising approach to develop safe nanoparticles capable of targeted drug delivery for various diseases. In this work, we have synthesized a lipid-based nanoparticle (NPs) that we have called "Aposomes" presenting native apolipoprotein B-100 (apoB-100), the primary protein present in Low-Density Lipoproteins (LDL) on its surface. The aposomes were synthesized from LDL isolated from blood plasma using a microfluidic approach.

Tutorial: using nanoneedles for intracellular delivery.

Intracellular delivery of advanced therapeutics, including biologicals and supramolecular agents, is complex because of the natural biological barriers that have evolved to protect the cell. Efficient delivery of therapeutic nucleic acids, proteins, peptides and nanoparticles is crucial for clinical adoption of emerging technologies that can benefit disease treatment through gene and cell therapy. Nanoneedles are arrays of vertical high-aspect-ratio nanostructures that can precisely manipulate complex processes at the cell interface, enabling effective intracellular delivery.

Biomimetic Nanoparticles as a Theranostic Tool for Traumatic Brain Injury.

Traumatic brain injury (TBI) triggers both central and peripheral inflammatory responses. Existing pharmacological drugs are unable to effectively and quickly target the brain inflamed regions, setting up a major roadblock towards effective brain trauma treatments. Nanoparticles (NPs) have been used in multiple diseases as drug delivery tools with remarkable success due to their rapid diffusion and specificity in the target organ.

Enhancing Inflammation Targeting Using Tunable Leukocyte-Based Biomimetic Nanoparticles.

Biomimetic nanoparticles aim to effectively emulate the behavior of either cells or exosomes. Leukocyte-based biomimetic nanoparticles, for instance, incorporate cell membrane proteins to transfer the natural tropism of leukocytes to the final delivery platform. However, tuning the protein integration can affect the behavior of these nanoparticles and alter their efficacy.

Phosphoprotein-based biomarkers as predictors for cancer therapy.

Disparities in cancer patient responses have prompted widespread searches to identify differences in sensitive vs. nonsensitive populations and form the basis of personalized medicine. This customized approach is dependent upon the development of pathway-specific therapeutics in conjunction with biomarkers that predict patient responses.

Liposome-Embedding Silicon Microparticle for Oxaliplatin Delivery in Tumor Chemotherapy.

Mesoporous silicon microparticles (MSMPs) can incorporate drug-carrying nanoparticles (NPs) into their pores. An NP-loaded MSMP is a multistage vector (MSV) that forms a Matryoshka-like structure that protects the therapeutic cargo from degradation and prevents its dilution in the circulation during delivery to tumor cells. We developed an MSV constituted by 1 µm discoidal MSMPs embedded with PEGylated liposomes containing oxaliplatin (oxa) which is a therapeutic agent for colorectal cancer (CRC).

Leukocyte-mimicking nanovesicles for effective doxorubicin delivery to treat breast cancer and melanoma.

In the last decades, several approaches were developed to design drug delivery systems to address the multiple biological barriers encountered after administration while safely delivering a payload. In this scenario, bio-inspired and bio-mimetic approaches have emerged as promising solutions to evade the mononuclear phagocytic system while simultaneously negotiating the sequential transport across the various biological barriers. Leukocytes freely circulate in the bloodstream and selectively target the inflamed vasculature in response to injury, infection, and cancer.

Biomimetic nanoparticles with enhanced affinity towards activated endothelium as versatile tools for theranostic drug delivery.

Activation of the vascular endothelium is characterized by increased expression of vascular adhesion molecules and chemokines. This activation occurs early in the progression of several diseases and triggers the recruitment of leukocytes. Inspired by the tropism of leukocytes, we investigated leukocyte-based biomimetic nanoparticles (i.

Engineered biomimetic nanovesicles show intrinsic anti-inflammatory properties for the treatment of inflammatory bowel diseases.

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a chronic inflammatory condition of the gastrointestinal (GI) tract. Currently, it is treated with immunosuppressant or biologics that often induce severe adverse effects. Thus, there is an urgent clinical need for more specific treatments.

Enhancing Vascularization through the Controlled Release of Platelet-Derived Growth Factor-BB.

Using delivery systems to control the in vivo release of growth factors (GFs) for tissue engineering applications is extremely desirable as the clinical use of GFs is limited by their fast in vivo turnover. Hence, the development of effective platforms that are able to finely control the release of GFs in vivo remains a challenge. Herein, we investigated the ability of multiscale microspheres, composed by a nanostructured silicon multistage vector (MSV) core and a poly(dl-lactide-co-glycolide) acid (PLGA) forming outer shell (PLGA-MSV), to release functional platelet-derived growth factor-BB (PDGF-BB) to induce in vivo localized neovascularization.

Unveiling the in Vivo Protein Corona of Circulating Leukocyte-like Carriers.

Understanding interactions occurring at the interface between nanoparticles and biological components is an urgent challenge in nanomedicine due to their effect on the biological fate of nanoparticles. After the systemic injection of nanoparticles, a protein corona constructed by blood components surrounds the carrier's surface and modulates its pharmacokinetics and biodistribution. Biomimicry-based approaches in nanotechnology attempt to imitate what happens in nature in order to transfer specific natural functionalities to synthetic nanoparticles.

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.

PLGA-Mesoporous Silicon Microspheres for the in Vivo Controlled Temporospatial Delivery of Proteins.

In regenerative medicine, the temporospatially controlled delivery of growth factors (GFs) is crucial to trigger the desired healing mechanisms in the target tissues. The uncontrolled release of GFs has been demonstrated to cause severe side effects in the surrounding tissues. The aim of this study was to optimize a translational approach for the fine temporal and spatial control over the release of proteins, in vivo.

Biodegradable nanoneedles for localized delivery of nanoparticles in vivo: exploring the biointerface.

Nanoneedles display potential in mediating the delivery of drugs and biologicals, as well as intracellular sensing and single-cell stimulation, through direct access to the cell cytoplasm. Nanoneedles enable cytosolic delivery, negotiating the cell membrane and the endolysosomal system, thus overcoming these major obstacles to the efficacy of nanotherapeutics. The low toxicity and minimal invasiveness of nanoneedles have a potential for the sustained nonimmunogenic delivery of payloads in vivo, provided that the development of biocompatible nanoneedles with a simple deployment strategy is achieved.

Leveraging nanochannels for universal, zero-order drug delivery in vivo.

Drug delivery is essential to achieve effective therapy. Herein we report on the only implantable nanochannel membrane with geometrically defined channels as small as 2.5 nm that achieves constant drug delivery in vivo.

Agarose surface coating influences intracellular accumulation and enhances payload stability of a nano-delivery system.

Purpose: Protein therapeutics often require repeated administrations of drug over a long period of time. Protein instability is a major obstacle to the development of systems for their controlled and sustained release. We describe a surface modification of nanoporous silicon particles (NSP) with an agarose hydrogel matrix that enhances their ability to load and release proteins, influencing intracellular delivery and preserving molecular stability.

Multi-composite bioactive osteogenic sponges featuring mesenchymal stem cells, platelet-rich plasma, nanoporous silicon enclosures, and Peptide amphiphiles for rapid bone regeneration.

A novel bioactive sponge was created with a composite of type I collagen sponges or porous poly(e-caprolactone) (PCL) scaffolds, platelet-rich plasma (PRP), BMP2-loaded nanoporous silicon enclosure (NSE) microparticles, mineralizing peptide amphiphiles (PA), and mesenchymal stem cells (MSC). Primary MSC from cortical bone (CB)  tissue proved to form more and larger colony units, as well as produce more mineral matrix under osteogenic differentiation, than MSC from bone marrow (BM). Coating pre-treatments were optimized for maximum cell adhesion and mineralization, while a PRP-based gel carrier was created to efficiently deliver and retain MSC and  microparticles within a porous scaffold while simultaneously promoting cell recruitment, proliferation, and angiogenesis.

A robust nanofluidic membrane with tunable zero-order release for implantable dose specific drug delivery.

This manuscript demonstrates a mechanically robust implantable nanofluidic membrane capable of tunable long-term zero-order release of therapeutic agents in ranges relevant for clinical applications. The membrane, with nanochannels as small as 5 nm, allows for the independent control of both dosage and mechanical strength through the integration of high-density short nanochannels parallel to the membrane surface with perpendicular micro- and macrochannels for interfacing with the ambient solutions. These nanofluidic membranes are created using precision silicon fabrication techniques on silicon-on-insulator substrates enabling exquisite control over the monodispersed nanochannel dimensions and surface roughness.

Enabling individualized therapy through nanotechnology.

Individualized medicine is the healthcare strategy that rebukes the idiomatic dogma of 'losing sight of the forest for the trees'. We are entering a new era of healthcare where it is no longer acceptable to develop and market a drug that is effective for only 80% of the patient population. The emergence of "-omic" technologies (e.