Vascularized tumor models for the evaluation of drug delivery systems: a paradigm shift.

As the conversion rate of preclinical studies for cancer treatment is low, user-friendly models that mimic the pathological microenvironment and drug intake with high throughput are scarce. Animal models are key, but an alternative to reduce their use would be valuable. Vascularized tumor-on-chip models combine great versatility with scalable throughput and are easy to use.

Navigating the landscape of RNA delivery systems in cardiovascular disease therapeutics.

Cardiovascular diseases (CVDs) stand as the leading cause of death worldwide, posing a significant global health challenge. Consequently, the development of innovative therapeutic strategies to enhance CVDs treatment is imperative. RNA-based therapies, encompassing non-coding RNAs, mRNA, aptamers, and CRISPR/Cas9 technology, have emerged as promising tools for addressing CVDs.

Fibroblasts mediate endothelium response to angiogenic cues in a newly developed 3D stroma engineered model.

Three-dimensional stroma engineered models would enable fundamental and applicative studies of human tissues interaction and remodeling in both physiological and pathological conditions. In this work, we propose a 3D vascularized stroma model to be used as in vitro platform for drug testing. A pullulan/dextran-based porous scaffold containing pre-patterned microchannels of 100 μm diameter is used for co-culturing of fibroblasts within the matrix pores and endothelial cells to form the lumen.

Advances in the engineering of the outer blood-retina barrier: From in-vitro modelling to cellular therapy.

The outer blood-retina barrier (oBRB), crucial for the survival and the proper functioning of the overlying retinal layers, is disrupted in numerous diseases affecting the retina, leading to the loss of the photoreceptors and ultimately of vision. To study the oBRB and/or its degeneration, many oBRB models have been developed, notably to investigate potential therapeutic strategies against retinal diseases. Indeed, to this day, most of these pathologies are untreatable, especially once the first signs of degeneration are observed.

Engineered human liver based on pullulan-dextran hydrogel promotes mice survival after liver failure.

Liver tissue engineering approaches aim to support drug testing, assistance devices, or transplantation. However, their suitability for clinical application remains unsatisfactory. Herein, we demonstrate the beneficial and biocompatible use of porous pullulan-dextran hydrogel for the self-assembly of hepatocytes and biliary-like cells into functional 3D microtissues.

Spatial-Controlled Coating of Pro-Angiogenic Proteins on 3D Porous Hydrogels Guides Endothelial Cell Behavior.

In tissue engineering, the composition and the structural arrangement of molecular components within the extracellular matrix (ECM) determine the physical and biochemical features of a scaffold, which consequently modulate cell behavior and function. The microenvironment of the ECM plays a fundamental role in regulating angiogenesis. Numerous strategies in tissue engineering have attempted to control the spatial cues mimicking in vivo angiogenesis by using simplified systems.

A Preclinical Validation of Iron Oxide Nanoparticles for Treatment of Perianal Fistulizing Crohn's Disease.

Fistulizing anoperineal lesions are severe complications of Crohn's disease (CD) that affect quality of life with a long-term risk of anal sphincter destruction, incontinence, permanent stoma, and anal cancer. Despite several surgical procedures, they relapse in about two-thirds of patients, mandating innovative treatments. Ultrasmall particles of iron oxide (USPIO) have been described to achieve in vivo rapid healing of deep wounds in the skin and liver of rats thanks to their nanobridging capability that could be adapted to fistula treatment.

Tuning Physicochemical Properties of a Macroporous Polysaccharide-Based Scaffold for 3D Neuronal Culture.

Central nervous system (CNS) lesions are a leading cause of death and disability worldwide. Three-dimensional neural cultures in biomaterials offer more physiologically relevant models for disease studies, toxicity screenings or in vivo transplantations. Herein, we describe the development and use of pullulan/dextran polysaccharide-based scaffolds for 3D neuronal culture.

In Vitro Strategies to Vascularize 3D Physiologically Relevant Models.

Vascularization of 3D models represents a major challenge of tissue engineering and a key prerequisite for their clinical and industrial application. The use of prevascularized models built from dedicated materials could solve some of the actual limitations, such as suboptimal integration of the bioconstructs within the host tissue, and would provide more in vivo-like perfusable tissue and organ-specific platforms. In the last decade, the fabrication of vascularized physiologically relevant 3D constructs has been attempted by numerous tissue engineering strategies, which are classified here in microfluidic technology, 3D coculture models, namely, spheroids and organoids, and biofabrication.

Membranes for Guided Bone Regeneration: A Road from Bench to Bedside.

Bone resorption can negatively influence the osseointegration of dental implants. Barrier membranes for guided bone regeneration (GBR) are used to exclude nonosteogenic tissues from influencing the bone healing process. In addition to the existing barrier membranes available on the market, a growing variety of membranes for GBR with tailorable physicochemical properties are under preclinical evaluation.

Development of 3D Hepatic Constructs Within Polysaccharide-Based Scaffolds with Tunable Properties.

Organoids production is a key tool for in vitro studies of physiopathological conditions, drug-induced toxicity assays, and for a potential use in regenerative medicine. Hence, it prompted studies on hepatic organoids and liver regeneration. Numerous attempts to produce hepatic constructs had often limited success due to a lack of viability or functionality.

Metal-Organic Framework Microsphere Formulation for Pulmonary Administration.

Although nanoscaled metal-organic frameworks (nanoMOFs) are promising drug carriers, their appropriate formulation remains almost unexplored and basically restricted to intravenous routes. Lungs, beneficiating from a large absorption surface and low enzymatic presence, are a very attractive target for both local and systemic delivery. However, pulmonary nanoMOF formulation is a pending and defying task.

Bimodal Fucoidan-Coated Zinc Oxide/Iron Oxide-Based Nanoparticles for the Imaging of Atherothrombosis.

A polyol method was used to obtain ultrasmall ZnO nanoparticles (NPs) doped with iron ions and coated with a low molecular weight fucoidan in order to perform in vivo MR and ex vivo fluorescence imaging of athrothrombosis. During the synthesis, the early elimination of water by azeotropic distillation with toluene allowed us to produce NPs which size, determined by XRD and TEM, decreased from 7 nm to 4 nm with the increase of iron/zinc ratios from 0.05 to 0.

GraftFast Surface Engineering to Improve MOF Nanoparticles Furtiveness.

Controlling the outer surface of nanometric metal-organic frameworks (nanoMOFs) and further understanding the in vivo effect of the coated material are crucial for the convenient biomedical applications of MOFs. However, in most studies, the surface modification protocol is often associated with significant toxicity and/or lack of selectivity. As an alternative, how the highly selective and general grafting GraftFast method leads, through a green and simple process, to the successful attachment of multifunctional biopolymers (polyethylene glycol (PEG) and hyaluronic acid) on the external surface of nanoMOFs is reported.

Nanoparticles of Metal-Organic Frameworks: On the Road to In Vivo Efficacy in Biomedicine.

In the past few years, numerous studies have demonstrated the great potential of nano particles of metal-organic frameworks (nanoMOFs) at the preclinical level for biomedical applications. Many of them were reported very recently based on their bioactive composition, anticancer application, or from a general drug delivery/theranostic perspective. In this review, the authors aim at providing a global view of the studies that evaluated MOFs' biomedical applications at the preclinical stage, when in vivo tests are described either for pharmacological applications or for toxicity evaluation.

Abiotic Sequence-Coded Oligomers as Efficient In Vivo Taggants for the Identification of Implanted Materials.

Sequence-defined oligourethanes were tested as in vivo taggants for implant identification. The oligomers were prepared in an orthogonal solid-phase iterative approach and thus contained a coded monomer sequence that can be unequivocally identified by tandem mass spectrometry (MS/MS). The oligomers were then included in small amounts (1 wt %) in square-centimeter-sized crosslinked poly(vinyl alcohol) (PVA) model films, which were intramuscularly and subcutaneously implanted in the abdomen of rats.

A Smart Metal-Organic Framework Nanomaterial for Lung Targeting.

Despite high morbidity and mortality associated with lung diseases, addressing drugs towards lung tissue remains a pending task. Particle lung filtration has been proposed for passive lung targeting and drug delivery. However, toxicity issues derived from the long-term presence of the particles must be overcome.

Cardiovascular Bio-Engineering: Current State of the Art.

Despite the introduction of new drugs and innovative devices contributing in the last years to improve patients' quality of life, morbidity and mortality from cardiovascular diseases remain high. There is an urgent need for addressing the underlying problem of the loss of cardiac or vascular tissues and therefore developing new therapies. Autologous vascular transplants are often limited by poor quality of donor sites and heart organ transplantation by donor shortage.

Transplantation of adipose-derived stem cells combined with neuregulin-microparticles promotes efficient cardiac repair in a rat myocardial infarction model.

Tissue engineering is a promising strategy to promote heart regeneration after a myocardial infarction (MI). In this study, we investigated the reparative potential of a system that combines adipose-derived stem cells (ADSCs) with microparticles (MPs) loaded with neuregulin (NRG), named ADSC-NRG-MPs, on a rat MI model. First, cells were attached to the surface of MPs encapsulating NRG and coated with a 1:1 mixture of collagen and poly-d-lysine.

Cytokine-loaded PLGA and PEG-PLGA microparticles showed similar heart regeneration in a rat myocardial infarction model.

Neuregulin (NRG1) and fibroblast growth factor (FGF1) are well known growth factors implicated in cardiomyocyte proliferation and survival, as well as in angiogenesis, the development of adult heart and the maintenance of cardiac function. NRG1 and FGF1 have become promising therapeutic agents to treat myocardial infarction (MI) disorder. Unfortunately, clinical trials performed so far reported negative efficacy results, because growth factors are rapidly degraded and eliminated from the biological tissues once administered.

Polymeric electrospun scaffolds: neuregulin encapsulation and biocompatibility studies in a model of myocardial ischemia.

Cardiovascular disease represents one of the major health challenges in modern times and is the number one cause of death globally. Thus, numerous studies are under way to identify effective cell- and/or growth factor (GF)-based therapies for repairing damaged cardiac tissue. In this regard, improving the engraftment or survival of regenerative cells and prolonging GF exposure have become fundamental goals in advancing these therapeutic approaches.

Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration.

Acidic fibroblast growth factor (FGF1) and neuregulin-1 (NRG1) are growth factors involved in cardiac development and regeneration. Microparticles (MPs) mediate cytokine sustained release, and can be utilized to overcome issues related to the limited therapeutic protein stability during systemic administration. We sought to examine whether the administration of microparticles (MPs) containing FGF1 and NRG1 could promote cardiac regeneration in a myocardial infarction (MI) rat model.

Vascular endothelial growth factor-loaded injectable hydrogel enhances plasticity in the injured spinal cord.

We hypothesized that vascular endothelial growth factor (VEGF)-containing hydrogels that gelify in situ after injection into a traumatized spinal cord, could stimulate spinal cord regeneration. Injectable hydrogels composed of 0.5% Pronova UPMVG MVG alginate, supplemented or not with fibrinogen, were used.

Injectable alginate hydrogel loaded with GDNF promotes functional recovery in a hemisection model of spinal cord injury.

We hypothesized that local delivery of GDNF in spinal cord lesion via an injectable alginate hydrogel gelifying in situ would support spinal cord plasticity and functional recovery. The GDNF release from the hydrogel was slowed by GDNF encapsulation in microspheres compared to non-formulated GDNF (free GDNF). When injected in a rat spinal cord hemisection model, more neurofilaments were observed in the lesion when the rats were treated with free GDNF-loaded hydrogels.