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Nanotechnology has shown tremendous success in the drug delivery field for more effective and safer therapy, and has recently enabled the clinical approval of RNA medicine, a new class of therapeutics. Various nanoparticle strategies have been developed to improve the systemic delivery of therapeutics, among which surface modification of targeting ligands on nanoparticles has been widely explored for 'active' delivery to a specific organ or diseased tissue. Meanwhile, compelling evidence has recently been reported that organ-selective targeting may also be achievable by systemic administration of nanoparticles without surface ligand modification. In this Review, we highlight this unique set of 'passive' nanoparticles and their compositions and mechanisms for organ-selective delivery. In particular, the lipid-based, polymer-based, and biomimetic nanoparticles with tropism to different specific organs after intravenous administration are summarized. The underlying mechanisms (e.g., protein corona and size effect) of these nanosystems for organ selectivity are also extensively discussed. We further provide perspectives on the opportunities and challenges in this exciting area of organ-selective systemic nanoparticle delivery. [ABSTRACT FROM AUTHOR]

The article focuses on the development of a biomimetic hydrogel, called EKGel, as an alternative to basement membrane extract (BME) for cultivating patient-derived breast tumor organoids (PDOs). Topics include the properties and advantages of EKGel, its effectiveness in supporting breast PDOs, and its potential applications in cancer research and drug development, offering improved stability and reduced contamination compared to BME-based cultures.

Aims: In 2003, an Australian woman was convicted by a jury of smothering and killing her four children over a 10-year period. Each child died suddenly and unexpectedly during a sleep period, at ages ranging from 19 days to 18 months. In 2019 we were asked to investigate if a genetic cause could explain the children's deaths as part of an inquiry into the mother's convictions.Methods and Results: Whole genomes or exomes of the mother and her four children were sequenced. Functional analysis of a novel CALM2 variant was performed by measuring Ca2+-binding affinity, interaction with calcium channels and channel function. We found two children had a novel calmodulin variant (CALM2 G114R) that was inherited maternally. Three genes (CALM1-3) encode identical calmodulin proteins. A variant in the corresponding residue of CALM3 (G114W) was recently reported in a child who died suddenly at age 4 and a sibling who suffered a cardiac arrest at age 5. We show that CALM2 G114R impairs calmodulin's ability to bind calcium and regulate two pivotal calcium channels (CaV1.2 and RyR2) involved in cardiac excitation contraction coupling. The deleterious effects of G114R are similar to those produced by G114W and N98S, which are considered arrhythmogenic and cause sudden cardiac death in children.Conclusion: A novel functional calmodulin variant (G114R) predicted to cause idiopathic ventricular fibrillation, catecholaminergic polymorphic ventricular tachycardia, or mild long QT syndrome was present in two children. A fatal arrhythmic event may have been triggered by their intercurrent infections. Thus, calmodulinopathy emerges as a reasonable explanation for a natural cause of their deaths. [ABSTRACT FROM AUTHOR]

Towards the repair of damaged tissues, numerous scaffolds have been fabricated to recreate the complex extracellular matrix (ECM) environment to support desired cell behaviors; however, it is often challenging to design scaffolds with the requisite cell-anchorage sites, mechanical stability, and tailorable physicochemical properties necessary for many applications. To address this and to improve on the properties of hyaluronic acid (HA) hydrogels, we combined photocrosslinkable norbornene-modified HA (NorHA) with human platelet lysate (PL). These PL-NorHA hybrid hydrogels supported the adhesion of cells when compared to NorHA hydrogels without PL, exhibited tailorable physicochemical properties based on the concentration of individual components, and released proteins over time. Using microfluidic techniques with on-chip mixing of NorHA and PL and subsequent photocrosslinking, spherical PL-NorHA microgels with a hierarchical fibrillar network were fabricated that exhibited the sustained delivery of PL proteins. Microgels could be jammed into granular hydrogels that exhibited shear-thinning and self-healing properties, enabling ejection from syringes and the fabrication of stable 3D constructs with 3D printing. Again, the inclusion of PL enhanced cellular interactions with the microgel structures. Overall, the combination of biomolecules and fibrin self-assembly arising from the enriched milieu of PL-derived proteins improved the bioactivity of HA-based hydrogels, enabling the formation of dynamic systems with modular design. The granular systems can be engineered to meet the complex demands of functional tissue repair using versatile processing techniques, such as with 3D printing. Image, graphical abstract [ABSTRACT FROM AUTHOR]

The surface chemistry of cellulose nanocrystals was engineered to show variable sulfation degrees, which was exploited to modulate platelet lysate-derived biomolecule sequestration and presentation. The protein coronas developed on CNC surfaces were characterized and it was demonstrated how they promote different signaling effects on human adipose-derived stem cell behavior. [ABSTRACT FROM AUTHOR]

Blood components play key roles in the modulation of the wound healing process and, together with the provisional fibrin matrix ability to selectively bind bioactive molecules and control its spatial-temporal presentation, define the complex microenvironment that characterize this biological process. As a biomimetic approach, the use of blood derivatives in regenerative strategies has awakened as a source of multiple therapeutic biomolecules. Nevertheless, and despite their clinical relevance, blood derivatives have been showing inconsistent therapeutic results due to several factors, including proper control over their delivery mechanisms. Herein, we highlight recent trends on the use biomaterials to protect, sequester and deliver these pools of biomolecules in tissue engineering and regenerative medicine approaches. Particular emphasis is given to strategies that enable to control their spatiotemporal delivery and improve the selectivity of presentation profiles of the biomolecules derived from blood derivatives rich in platelets. Finally, we discussed possible directions for biomaterials design to potentiate the aimed regenerative effects of blood derivatives and achieve efficient therapies. [ABSTRACT FROM AUTHOR]

Magnetic biomaterials are a key focus in medical research. Tropoelastin is the soluble precursor of elastin and is a critical component of tissues requiring elasticity as part of their physiological function. By utilising the versatility of tropoelastin and the ability to tailor its properties, we developed a novel magnetic spongy-like hydrogel based on tropoelastin doped with magnetic properties by in situ precipitation method. The presence of magnetic nanoparticles altered the secondary structure of tropoelastin. Bioengineered tropoelastin-based magnetic spongy-like hydrogels displayed a homogenous distribution of magnetic nanoparticles throughout the tropoelastin network and quick magnetic responsiveness to an applied external magnetic field. Morphologically, in the presence of magnetic nanoparticles, hydrated tropoelastin spongy-like hydrogels showed apparently smaller pore sizes and less swelling. Furthermore, in vitro biological studies using human tendon-derived cells revealed that magnetically responsive tropoelastin spongy-like hydrogels supported cell viability and enabled cell adhesion, spreading and migration into the interior of the spongy-like hydrogel up to two weeks. The bioengineered tropoelastin-based magnetic spongy-like hydrogel represents a novel class of hybrid biomaterial that can serve as a platform for soft tissue regeneration. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Lysophosphatidic Acid Mediates the Release of Cytokines and Chemokines by Human Fibroblasts Treated with Loxosceles Spider Venom," that was published in the February 28, 2013 issue of the "Journal of Investigative Dermatology."