E-cardiac patch to sense and repair infarcted myocardium.

Conductive cardiac patches can rebuild the electroactive microenvironment for the infarcted myocardium but their repair effects benefit by carried seed cells or drugs. The key to success is the effective integration of electrical stimulation with the microenvironment created by conductive cardiac patches. Besides, due to the concerns in a high re-admission ratio of heart patients, a remote medicine device will underpin the successful repair. Herein, we report a miniature self-powered biomimetic trinity triboelectric nanogenerator with a unique double-spacer structure that unifies energy harvesting, therapeutics, and diagnosis in one cardiac patch. Trinity triboelectric nanogenerator conductive cardiac patches improve the electroactivity of the infarcted heart and can also wirelessly monitor electrocardiosignal to a mobile device for diagnosis. RNA sequencing analysis from rat hearts reveals that this trinity cardiac patches mainly regulates cardiac muscle contraction-, energy metabolism-, and vascular regulation-related mRNA expressions in vivo. The research is spawning a device that truly integrates an electrical stimulation of a functional heart patch and self-powered e-care remote diagnostic sensor.

The mechanism of Shenbing Decoction II against IgA nephropathy renal fibrosis revealed by UPLC-MS/MS, network pharmacology and experimental verification.

Background: IgA nephropathy (IgAN) is a major and growing public health problem. Renal fibrosis plays a vital role in the progression of IgAN. This study is to investigate the mechanisms of action underlying the therapeutic effects of Shenbing Decoction II (SBDII) in IgAN renal fibrosis treatment based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), network pharmacology and experimental verification. Method: We first used UPLC-MS/MS to explore the main compounds of SBDII, and then used network pharmacology to predict the targets and key pathways of SBDII in the treatment of IgAN renal fibrosis. Next, bovine serum albumin (BSA), lipopolysaccharide (LPS), and carbon tetrachloride (CCL4) were used to induce IgAN in rats, and then biochemical indicators, renal tissue pathology, and renal fibrosis-related indicators were examined. At the same time, part of the results predicted by network pharmacology were also verified. Result: A total of 105 compounds were identified in SBDII by UPLC-MS/MS. Network pharmacology results showed that the active compounds such as acacetin, eupatilin, and galangin may mediate the therapeutic effects of SBDII in treating IgAN by targeting tumor protein p53 (TP53) and regulating phosphatidylinositol 3-kinase (PI3K)-Akt kinase (Akt) signaling pathway. Animal experiments showed that SBDII not only significantly improved renal function and fibrosis in IgAN rats, but also significantly downregulated the expressions of p53, p-PI3K and p-Akt. Conclusion: This UPLC-MS/MS, network pharmacological and experimental study highlights that the TP53 as a target, and PI3K-Akt signaling pathway are the potential mechanism by which SBDII is involved in IgAN renal fibrosis treatment. Acacetin, eupatilin, and galangin are probable active compounds in SBDII, these results might provide valuable guidance for further studies of IgAN renal fibrosis treatment.

Transdermal drug delivery via microneedles for musculoskeletal systems.

As the population is ageing and lifestyle is changing, the prevalence of musculoskeletal (MSK) disorders is gradually increasing with each passing year, posing a serious threat to the health and quality of the public, especially the elderly. However, currently prevalent treatments for MSK disorders, mainly administered orally and by injection, are not targeted to the specific lesion, resulting in low efficacy along with a series of local and systemic adverse effects. Microneedle (MN) patches loaded with micron-sized needle array, combining the advantages of oral administration and local injection, have become a potentially novel strategy for the administration and treatment of MSK diseases. In this review, we briefly introduce the basics of MNs and focus on the main characteristics of the MSK systems and various types of MN-based transdermal drug delivery (TDD) systems. We emphasize the progress and broad applications of MN-based transdermal drug delivery (TDD) for MSK systems, including osteoporosis, nutritional rickets and some other typical types of arthritis and muscular damage, and in closing summarize the future prospects and challenges of MNs application.

3D hypoxia-mimicking and anti-synechia hydrogel enabling promoted neovascularization for renal injury repair and regeneration.

In-situ renal tissue engineering is promising yet challenging for renal injury repair and regeneration due to the highly vascularized structure of renal tissue and complex high-oxidative stress and ischemic microenvironment. Herein, a novel biocompatible 3D porous hydrogel (DFO-gel) with sustained release capacity of hypoxia mimicking micromolecule drug deferoxamine (DFO) was developed for in-situ renal injury repair. In vitro and in vivo experimental results demonstrated that the developed DFO-gels can exert the synchronous benefit of scavenging excess reactive oxygen species (ROS) regulating inflammatory microenvironment and promoting angiogenesis for effective renal injury repair by up-regulating hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). The in-situ neogenesis of neonatal glomerular- and tubular-like structures in the implanted areas in the partially nephrectomized rats also suggested the potential for promoting renal injury repair and regeneration. This multifunctional hydrogel can not only exhibit the sustained release and promoted bio-uptake capacity for DFO, but also improve the renal injured microenvironment by alleviating oxidative and inflammatory stress, accelerating neovascularization, and promoting efficient anti-synechia. We believe this work offers a promising strategy for renal injury repair and regeneration.

A biomimetic double network hydrogel ameliorates renal fibrosis and promotes renal regeneration.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are serious global public health issues. Both interconnect closely, and AKI-CKD transition significantly increases the morbidity of CKD and inevitably progresses to end stage renal disease. However, with the current drug delivery system it is hard to achieve precise delivery and apply it to clinical practice due to the local fibrotic milieu of the AKI-CKD transition procedure. Consequently, new treatment options to halt or even reverse AKI-CKD transition are urgently needed. Curcumin and Ac-SDKP were proved to be capable of ameliorating renal injury and restoring renal biological function. However, due to the water-insolubility, poor absorption and ease of degradation features, their utilization based on traditional drug delivery systems was still confined to the laboratory. A new approach for the targeted delivery of curcumin and Ac-SDKP into kidneys is needed. Hydrogels, owing to their capability of targeted-drug delivery and bio-favorable nature, emerge as a promising resolution. Herein, we developed a bioinspired double network hydrogel scaffold loaded with curcumin and N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) to explore the feasibility of drug-loaded hydrogels for treatment of AKI-CKD transition. This double network hydrogel (GCS) was prepared based on gelatin and curcumin-zinc with polydopamine (DOPA) coating and then immobilized with Ac-SDKP on the surface. The prepared hydrogels possessed appropriate porosity, suitable mechanical properties, and excellent biocompatibility. In vitro, the GCS hydrogel was demonstrated to be pro-angiogenic, anti-oxidative and anti-fibrotic. In vivo, after the GCS hydrogel was implanted into partially nephrectomized rat kidneys, local renal fibrosis was observed to be improved significantly, and neo-blood vessels and neonatal renal tubules appeared around the implanted area. We speculated that the GCS hydrogel could ameliorate renal fibrosis and injury significantly and stimulate regeneration in situ. Taken together, this study demonstrated the promising potential of this bioinspired hydrogel scaffold for renal injury repair and renal regeneration.

[Preliminary study on premixed materials of emulsion gel].

The purpose of this paper was to study the pre-mixed materials of emulsion gel. Accessories were screened and formula was designed with the most common use, low cost and simple process as the standards. Experiments were designed by central composite design-response surface methodology (ccd-rsm). 8.0.6 Trial Design-Expert was used for data processing and analysis, and subjective scores were used as the index to draw the three-dimensional effect surface and 2D contour maps. It was determined that the optimal ranges were A (carbomer 940)： 0.05-0.065 g; B (castor oil)： 1.00-1.12 mL; C (poly polysorbate-80)： 0.15 mL. The optimal formula was as follows： carbopol 0.057 5 g, castor oil 1.1 mL, polysorbate-80 0.15 mL. The formulated substrate was studied on its preliminary stability and rheology characteristics, such as viscosity and thixotropy. Then with the optimal formula as substrate, emulsion type gel was prepared respectively with 98% rutin, 98% berberine hydrochloride, and 98% berbamine hydrochloride as the main component. With 0.9% normal saline as the absorption solution, the results showed that the ransdermal flux of the three formulations of 1 h was all less than 1%. The results indicated that this substrate had the potential to be developed into a premixed material. The emulsion type gel matrix made from this formula had a good appearance, stability to certain extent, appropriate viscosity and thixotropy, and showed no skin irritation in 1 h.