High-aspect-ratio polymeric micelles (filomicelles, FMs) are attractive anisotropic nanoparticles for a wide range of applications, however, their formation is typically confined to narrow hydrophilic/hydrophobic polymer block ratios, limiting systematic structure-property investigations. Consequently, independent control over micelle width, length, and stiffness remains challenging. A supramolecular polymerization-induced self-assembly (PISA) strategy using a bis-urea core template was recently...
Human tissue engineering holds great promise for creating physiological models while facing challenges replicating natural complexity, including cellular and extracellular cues. Current approaches often miss the incorporation of major bioengineering factors (i.e., cellular complexity, well-defined extracellular matrix (ECM) mimicry, dynamic stimuli). We bioengineered liver tissues (BLTs) utilizing human intrahepatic cholangiocyte organoids (ICOs), hepatic stellate cells (HSCs), and mesenchymal...
A major goal of clinically oriented CRISPR-Cas9-based applications is safe and effective in vivo gene editing (knockout or correction) with precise targeting. Substantial efforts have been devoted to the preclinical development of novel drug delivery platforms that enable efficient, targeted delivery. However, the immune responses induced by CRISPR-Cas9 treatment are often overlooked. Preexisting immunity to clinically relevant Cas9 proteins has already been established as a consequence of...
The gene editing enzyme SpCas9 was engineered to display azide on its surface, enabling azide-alkyne click conjugation. As a proof of concept, siRNA functionalized with a reduction sensitive linker and ring-strained alkyne tetramethylthiocycloheptyne sulfoximine was conjugated to SpCas9 on four different residues with varying efficiency and retained protein activity. Conjugation to residue 539 was successful and site-selective while retaining SpCas9 and siRNA bioactivity.
BACKGROUND: The enteric nervous system (ENS) plays a pivotal role not only in gastrointestinal function but also in neurodegenerative diseases through bidirectional communication with the central nervous system along the gut-brain axis. Enteric glial cells are central to ENS function, acting as key regulators of neuroimmune interactions. Enteric glial cell metabolism likely plays an important role in these functions. However, how pro- or anti-inflammatory stimuli influence enteric glial cell...
Obeticholic acid (OCA), a potent agonist of the bile salt-activated nuclear receptor farnesoid X receptor (FXR), accelerates liver hypertrophy after portal vein embolization (PVE), but the mechanisms underlying this effect are incompletely understood. In a rabbit model of PVE, New Zealand White rabbits received OCA (10 mg/kg/day) or vehicle by oral gavage before and after embolization. We quantified systemic and hepatic bile salt pools, profiled FXR-regulated genes in ileum and liver, and...
In cartilage tissue engineering, there is a growing interest in dynamic hydrogels that promote spheroid fusion and cartilaginous matrix deposition, while maintaining sufficient stability for long-term construct maturation. In this study, Diels-Alder click chemistry is employed as a dynamic-covalent crosslinking method to create hydrogels composed of hyaluronic acid, gelatin, and PEG. By adjusting the pH during crosslinking, the tuneability of hydrogel stiffness and stability at pH values around...
Targeted delivery of mRNA therapeutics offers immense potential for improving treatment efficacy while reducing off-target effects. Despite extensive efforts to develop both passive and active targeting strategies, achieving precise and efficient mRNA delivery remains a significant challenge due to rapid clearance, endosomal entrapment, and nonspecific tissue distribution. This study explores magnetic lipid nanoparticles (mLNPs) as an advanced platform for in vivo mRNA delivery. By incorporating...
As precision medicine advances, the need for customizable drug delivery systems has become increasingly important. In this study, we developed porous tablets as substrates for drop-on dispensing of drug-containing ink in personalized doses. We evaluated this approach with clonidine hydrochloride, a hydrophilic drug prescribed in low doses for pediatric patients with hypertension. Porous tablets were compacted from functionalized calcium carbonate (FCC), a filler with a mesoporous structure that...
