Exosomes from Hypoxia Preconditioned Muscle-Derived Stem Cells Enhance Cell-Free Corpus Cavernosa Angiogenesis and Reproductive Function Recovery.

Tissue engineering for penile corpora cavernosa defects requires microvascular system reconstruction.GelMA hydrogels show promise for tissue regeneration. However, using stem cells faces challenges such as immune rejection, limited proliferation and differentiation, and biosafety concerns. Therefore, acellular tissue regeneration may avoid these issues. Exosomes are used from muscle-derived stem cells (MDSCs) to modify 3D-printed hydrogel scaffolds for acellular tissue regeneration. Hypoxia-preconditioned MDSC-derived exosomes are obtained to enhance the therapeutic effect. In contrast to normoxic exosomes (N-Exos), hypoxic exosomes (H-Exos) are found to markedly enhance the proliferation, migration, and capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). High-throughput sequencing analysis of miRNAs isolated from both N-Exos and H-Exos revealed a significant upregulation of miR-21-5p in H-Exos following hypoxic preconditioning. Further validation demonstrated that the miR-21-5p/PDCD4 pathway promoted the proliferation of HUVECs. Epigallocatechin gallate (EGCG) is introduced to improve the mechanical properties and biocompatibility of GelMA hydrogels. EGCG-GelMA scaffolds loaded with different types of Exos are transplanted to repair rabbit penile corpora cavernosa defects, observed the blood flow and repair status of the defect site through color Doppler ultrasound and magnetic resonance imaging, and ultimately restored the rabbit penile erection function and successfully bred offspring. Thus, acellular hydrogel scaffolds offer an effective treatment for penile corpora cavernosa defects.

Effect of organic solvents on calcium minodronate crystal morphology in aqueous solution: an experimental and theoretical study.

The influence of nine organic solvents on the crystal morphology of calcium minodronate (Ca(Min)2) was investigated by experimental investigations and molecular simulations. Hirshfeld analysis was used to reveal the intermolecular interactions, and the modified attachment energy (AE) model was applied to constructing the Ca(Min)2-organic-water model in different organic-water solvents. The surface structure and the mass density profile were demonstrated and analyzed. The results showed that there were different adsorption conditions in different organic-water solvents. Furthermore, it was found that the (2 0 0)/(1 1 0) side ratio of Ca(Min)2 crystal had a linear relationship with the volume of organic solvent and had a certain correlation with some solvent properties. It is believed that the research developed in this work could have a promising application in prediction of Ca(Min)2 crystal morphology and could give guidance in the selection of organic solvents to control the desirable crystal morphology.

MicroRNA-126 engineered muscle-derived stem cells attenuates cavernosa injury-induced erectile dysfunction in rats.

BACKGROUND: Cavernosa injury is a common cause of organic erectile dysfunction (ED), which requires safe and effective treatments. In the present study, the therapeutic efficiency of muscle-derived stem cells (MDSCs) modified with microRNA-126 (miR-126) was determined in rats with cavernosa injury. METHODS: MDSCs were transfected with miR-126 and then were transplanted into rats with cavernosa injury. Erectile function, vascular function (western blot and immunofluorescence), extraction, and detection of exosomes were then undertaken. RESULTS: On the 28th day after transplantation, the highest value of intra-cavernous pressure (ICP)/mean arterial pressure (MAP) in rats of miRNA-126 group (0.84 ± 0.14) was observed (Control: 0.38 ± 0.07; MDSC: 0.54 ± 0.11, Vector: 0.60 ± 0.02; respectively). Treatment of miRNA-126-modified-MDSCs remarkably strengthened vascular structure, supported by hematoxylin-eosin staining. The expression of CD31, von Willebrand Factor and vascular endothelial factors were higher than those in other groups, indicating improved vascular function. In vitro mechanism studies showed that exosomes containing miR-126 isolated from MDSCs promoted angiogenesis and attenuated apoptosis of human umbilical venous endothelial cells. Finally, insulin receptor substrate 1 and Krüppel-like factor 10 were determined as the direct target genes of miR-126. CONCLUSIONS: MiR-126 engineered MDSCs notably repaired cavernosa injury in rats via vascular reconstruction by directly targeting IRS1 and KLF10, in which the exosomes secreted by MDSCs played a critical role.

A Biomimetic Biphasic Osteochondral Scaffold with Layer-Specific Release of Stem Cell Differentiation Inducers for the Reconstruction of Osteochondral Defects.

There is a great challenge in regenerating osteochondral defects because they involve lesions of both cartilage and subchondral bone, which have remarkable differences in their chemical compositions and biological lineages. Thus, considering the complicated requirements in osteochondral reconstruction, a biomimetic biphasic osteochondral scaffold (BBOS) with the layer-specific release of stem cell differentiation inducers are developed. The cartilage regeneration layer (cartilage scaffold, CS) in the BBOS contains a hyaluronic acid hydrogel to mimic the composition of cartilage, which is mechanically enhanced by host-guest supramolecular units to control the release of kartogenin (KGN). Additionally, a 3D-printed hydroxyapatite (HAp) scaffold releasing alendronate (ALN) is employed as the bone-regeneration layer (bone scaffold, BS). The two layers are bound by semi-immersion and could regulate the hierarchical targeted differentiation behavior of the stem cells. Compared to the drug-free scaffold, the MSCs in the BBOS could be promoted to differentiate into both chondrocytes and osteoblasts. The in vivo results demonstrate the strong promotion of cartilage or bone regeneration in their respective layers. It is expected that this BBOS with layer-specific inducer release can become a new strategy for osteochondral regeneration.

Liquid-liquid phase-change absorption of SO2 using N, N-dimethylcyclohexylamine as absorbent and liquid paraffin as solvent.

In the present work, liquid-liquid phase-change absorption of SO2 was investigated using N, N-dimethylcyclohexylamine (DMCHA) as an absorbent, and high boiling liquid paraffin (LP) as a solvent to reduce volatilization of the absorbent. The homogenous solution was split into two immiscible phases upon SO2 loading. The phase-change mechanism was attributed to the polarity variation of DMCHA before and after absorption by forming the charge-transfer complex DMCHA·SO2. The viscosity of the lower phase reached a maximum value of 24.5 mPa s at the absorption capacity of 1 mol SO2/mol DMCHA, and the viscosity of the corresponding upper phase was 46.4 mPa s. Both are lower than the reported viscosity of most ionic liquids. This solution exhibited extremely high mass selectivity of SO2/CO2 with a value of 626. The mass absorption capacity was founded to be 1.19 g SO2/g DMCHA at 1 atm, which is comparable with the highest reported mass absorption capacity. At low partial pressure, the absorption capacity still reached 0.78 g/g at 0.1 atm, 0.43 g/g at 0.02 atm and 0.27 g/g at 0.001 atm. Furthermore, DMCHA could be completely regenerated in 10 min via microwave heating. All the results indicated this phase-change solution is a promising candidate for SO2 capture.