Minimally invasive co-injection of modular micro-muscular and micro-vascular tissues improves in situ skeletal muscle regeneration.

Various conventional treatment strategies for volumetric muscle loss (VML) are often hampered by the extreme donor site morbidity, the limited availability of quality muscle flaps, and complicated, as well as invasive surgical procedures. The conventional biomaterial-based scaffolding systems carrying myoblasts have been extensively investigated towards improving the regeneration of the injured muscle tissues, as well as their injectable forms. However, the applicability of such designed systems has been restricted due to the lack of available vascular networks. Considering these facts, here we present the development of a unique set of two minimally invasively injectable modular microtissues, consisting of mouse myoblast (C2C12)-laden poly(lactic-co-glycolic acid) porous microspheres (PLGA PMs), or the micro-muscles, and human umbilical vein endothelial cell (HUVEC)-laden poly(ethylene glycol) hollow microrods (PEG HMs), or the microvessels. Besides systematic in vitro investigations, the myogenic performance of these modular composite microtissues, when co-injected, was explored in vivo using a mouse VML model, which confirmed improved in situ muscle regeneration and remolding. Together, we believe that the construction of these injectable modular microtissues and their combination for minimally invasive therapy provides a promising method for in situ tissue healing.

Biodegradable Quantum Composites for Synergistic Photothermal Therapy and Copper-Enhanced Chemotherapy.

In recent times, the combination therapy has garnered enormous interest owing to its great potential in clinical research. It has been reported that disulfiram, a clinical antialcoholism drug, could be degraded to diethyldithiocarbamate (DDTC) in vivo and subsequently result in the copper-DDTC complex (Cu(DDTC)2) toward ablating cancer cells. In addition, the ultrasmall copper sulfide nanodots (CuS NDs) have shown great potential in cancer treatment because of their excellent photothermal and photodynamic therapeutic efficiencies. Herein, by taking advantage of the interactions between CuS and DDTC, a new multifunctional nanoplatform based on DDTC-loaded CuS (CuS-DDTC) NDs is successfully fabricated, leading to the achievement of the synergistic effect of photothermal and copper enhanced chemotherapy. All experimental results verified promising synergistic therapeutic effects. Moreover, in vivo biocompatibility and metabolism experiments displayed that the CuS-DDTC NDs could be quickly excreted from the body with no apparent toxicity signs. Together, our findings indicated the superior synergistic therapeutic effect of photothermal and copper-enhanced chemotherapy, providing a promising anticancer strategy based on the CuS-DDTC NDs drug delivery system.

Near-Infrared-Activated Lysosome Pathway Death Induced by ROS Generated from Layered Double Hydroxide-Copper Sulfide Nanocomposites.

The overdeveloped lysosomes in cancer cells are gaining increasing attention toward more precise and effective organelle-targeted cancer therapy. It is suggested that rod/plate-like nanomaterials with an appropriate size exhibited a greater quantity and longer-term lysosomal enrichment, as the shape plays a notable role in the nanomaterial transmembrane process and subcellular behaviors. Herein, a biodegradable platform based on layered double hydroxide-copper sulfide nanocomposites (LDH-CuS NCs) is successfully prepared via in situ growth of CuS nanodots on LDH nanoplates. The as-prepared LDH-CuS NCs exhibited not only high photothermal conversion and near-infrared (NIR)-induced chemodynamic and photodynamic therapeutic efficacies, but also could achieve real-time in vivo photoacoustic imaging (PAI) of the entire tumor. LDH-CuS NCs accumulated in lysosomes would then generate extensive subcellular reactive oxygen species (ROS) in situ, leading to lysosomal membrane permeabilization (LMP) pathway-associated cell death both in vitro and in vivo.

Solution-enhanced dispersion by supercritical fluids: an ecofriendly nanonization approach for processing biomaterials and pharmaceutical compounds.

In recent years, the supercritical fluid (SCF) technology has attracted enormous interest from researchers over the traditional pharmaceutical manufacturing strategies due to the environmentally benign nature and economically promising character of SCFs. Among all the SCF-assisted processes for particle formation, the solution-enhanced dispersion by supercritical fluids (SEDS) process is perhaps one of the most efficient methods to fabricate the biomaterials and pharmaceutical compounds at an arbitrary gauge, ranging from micro- to nanoscale. The resultant miniature-sized particles from the SEDS process offer enhanced features concerning their physical attributes such as bioavailability enhancement due to their high surface area. First, we provide a brief description of SCFs and their behavior as an anti-solvent in SCF-assisted processing. Then, we aim to give a brief overview of the SEDS process as well as its modified prototypes, highlighting the pros and cons of the particular modification. We then emphasize the effects of various processing constraints such as temperature, pressure, SCF as well as organic solvents (if used) and their flow rates, and the concentration of drug/polymer, among others, on particle formation with respect to the particle size distribution, precipitation yield, and morphologic attributes. Next, we aim to systematically discuss the application of the SEDS technique in producing therapeutic nano-sized formulations by operating the drugs alone or in combination with the biodegradable polymers for the application focusing oral, pulmonary, and transdermal as well as implantable delivery with a set of examples. We finally summarize with perspectives.

The time-dependent synergism of the six-component mixtures of substituted phenols, pesticides and ionic liquids to Caenorhabditis elegans.

Traditional environmental risk assessment rarely focused on exposures to multi-component mixtures which may cause toxicological interactions and usually ignored that toxicity is a process in time, which may underestimate the environment risk of mixtures. In this paper, six chemicals belonging to three categories, two substituted phenols, two pesticides and two Ionic liquids, were picked to construct a six-component mixture system. To systematically examine the effects of various concentration compositions, the uniform design ray method was employed to design nine mixture rays with nine mixture ratios and for every mixture ray 12 concentration levels were specified by the fixed ratio ray design. The improved combination index was used to evaluate the combined toxicities of the mixtures to Caenorhabditis elegans (C. elegans) in the exposure times of 6, 12 and 24h. It was shown that the mixture rays display time-dependent synergism, i.e. the range of synergistic effect narrows and the strength of synergism runs down with exposure time, which illustrates that the mixture toxicity of some chemicals is not a sum of individual toxicities at some exposure times and it is necessary to consider the toxicological interaction in mixtures.