The menace of severe adverse events and deaths associated with viral gene therapy and its potential solution.

Over the past decade, in vivo gene replacement therapy has significantly advanced, resulting in market approval of numerous therapeutics predominantly relying on adeno-associated viral vectors (AAV). While viral vectors have undeniably addressed several critical healthcare challenges, their clinical application has unveiled a range of limitations and safety concerns. This review highlights the emerging challenges in the field of gene therapy. At first, we discuss both the role of biological barriers in viral gene therapy with a focus on AAVs, and review current landscape of in vivo human gene therapy. We delineate advantages and disadvantages of AAVs as gene delivery vehicles, mostly from the safety perspective (hepatotoxicity, cardiotoxicity, neurotoxicity, inflammatory responses etc.), and outline the mechanisms of adverse events in response to AAV. Contribution of every aspect of AAV vectors (genomic structure, capsid proteins) and host responses to injected AAV is considered and substantiated by basic, translational and clinical studies. The updated evaluation of recent AAV clinical trials and current medical experience clearly shows the risks of AAVs that sometimes overshadow the hopes for curing a hereditary disease. At last, a set of established and new molecular and nanotechnology tools and approaches are provided as potential solutions for mitigating or eliminating side effects. The increasing number of severe adverse reactions and, sadly deaths, demands decisive actions to resolve the issue of immune responses and extremely high doses of viral vectors used for gene therapy. In response to these challenges, various strategies are under development, including approaches aimed at augmenting characteristics of viral vectors and others focused on creating secure and efficacious non-viral vectors. This comprehensive review offers an overarching perspective on the present state of gene therapy utilizing both viral and non-viral vectors.

Thermal and Electrical Properties of Additively Manufactured Polymer-Boron Nitride Composite.

The efficiency of electronic microchip-based devices increases with advancements in technology, while their size decreases. This miniaturization leads to significant overheating of various electronic components, such as power transistors, processors, and power diodes, leading to a reduction in their lifespan and reliability. To address this issue, researchers are exploring the use of materials that offer efficient heat dissipation. One promising material is a polymer-boron nitride composite. This paper focuses on 3D printing using digital light processing of a model of a composite radiator with different boron nitride fillings. The measured absolute values of the thermal conductivity of such a composite in the temperature range of 3-300 K strongly depend on the concentration of boron nitride. Filling the photopolymer with boron nitride leads to a change in the behavior of the volt-current curves, which may be associated with the occurrence of percolation currents during the deposition of boron nitride. The ab initio calculations show the behavior and spatial orientation of BN flakes under the influence of an external electric field at the atomic level. These results demonstrate the potential use of photopolymer-based composite materials filled with boron nitride, which are manufactured using additive techniques, in modern electronics.

The Fabrication and Characterization of BaTiO3 Piezoceramics Using SLA 3D Printing at 465 nm Wavelength.

The additive manufacturing of BaTiO3 (BT) ceramics through stereolithography (SLA) 3D printing at 465 nm wavelength was demonstrated. After different milling times, different paste compositions with varied initial micron-sized powders were studied to find a composition suitable for 3D printing. The pastes were evaluated in terms of photopolymerization depth depending on the laser scanning speed. Furthermore, the microstructure and properties of the BT ceramic samples produced through SLA 3D printing were characterized and compared with those of ceramics fabricated through a conventional die semi-drying pressing method. Three-dimensional printed samples achieved relative densities over 0.95 and microhardness over 500 HV after sintering, nearly matching the relative density and microhardness attained by the pressed samples. Upon poling, the 3D-printed samples attained acceptable piezoelectric module d33 = 148 pC/N and dielectric constants over 2000. At near full density, BT piezoceramics were successfully fabricated through SLA 3D printing at 465 nm wavelength, achieving photopolymerization depth of more than 100 microns. This work paves the relatively low-cost way for 3D printing of piezoelectric ceramics using conventional micron-sized powders and high printed layer thickness.

Stereolithographic fabrication of three-dimensional permeable scaffolds from CaP/PEGDA hydrogel biocomposites for use as bone grafts.

Polyethylene glycol diacrylate-based hydrogels filled with calcium phosphates (CaP, Ca/P < 1.5) were stereolithographically fabricated as three-dimensional permeable biocomposites for bone tissue regeneration, probed by several instrumental techniques (including scanning electron microscopy, infrared and UV-vis spectroscopy), and subjected to rheological/mechanical property analysis. As the CaP content increased from 0 to 10 wt%, Young's modulus and mechanical strength increased from 4 to 11 kPa and from 34 to 167 kPa, respectively. Moreover, the enhanced elastic properties and tuneable swelling behaviour of the fabricated composites made them well suited for bone defect filling.