Long-Term Recruitment of Endogenous M2 Macrophages by Platelet Lysate-Rich Plasma Macroporous Hydrogel Scaffold for Articular Cartilage Defect Repair.

After cartilage damage, a large number of monocytes/macrophages infiltrate into adjacent synovium and the resident macrophages in synovial tissue transform to activated macrophages (M1), which secrete pro-inflammatory cytokines to induce sustained inflammation and chondrocyte apoptotic. However, current clinical therapies for cartilage repair can rarely achieve long-term anti-inflammatory regulation and satisfactory outcomes. Herein, a platelet lysate-rich plasma macroporous hydrogel (PLPMH) scaffold with around 100 µm pore size and 1.25 MPa Young's modulus is developed to sustainedly recruit and polarize endogenous anti-inflammatory macrophages (M2) for improving cartilage defect repair. PLPMH scaffold can steadily release sphingosine1-phosphate and proteins via gradual degradation, thus inducing M2 macrophages migration or resting (M0) macrophages migration and then polarization to M2 phenotype, and improving the secretion of anti-inflammatory cytokines. Furthermore, PLPMH scaffold exhibits negligible inflammatory responses in vivo and promotes endogenous M2 macrophage infiltration in large numbers and long-time duration to provide a local anti-inflammatory microenvironment, which even lasts for 42 d. In a rabbit model of cartilage defect, PLPMH scaffold increases the ratio of M2 macrophages and improves cartilage tissue regeneration. These studies support that PLPMH scaffold may have a great potential in articular cartilage tissue engineering by providing an anti-inflammatory and pro-regenerative microenvironment.

Biomimetic microcavity interfaces for a label-free capture of pathogens in the fluid bloodstream by vortical crossflow filtration.

Bacterial sepsis is a lethal disease triggered by microbial pathogens. The blood pathogen load is a major contributor to both disease severity and mortality in patients with sepsis blood. Therefore, it is crucial to reduce the load of pathogens, in particular the drug-resistant pathogens. In this work, inspired by the crossflow filtration mechanism in suspension-feeding fish, we developed a biomimetic microcavity interface to mimic a porous gill-raker surface as a blood-cleansing dialyzer for sepsis therapy, which can rapidly, safely and efficiently clear bacteria from the fluidic blood. The microcavity interface consists of microcavity arrays, the innerface of which contains nanowire forests. By precisely controlling the pore size of the microcavity and directing the axial travel of the fluid, the bacteria can be isolated from the whole blood without disturbing any blood components or blocking the blood cell transportation. In addition, the three-dimensional nanowire forests assist in the formation of vortices with reduced blood flow velocity and increased resistance to bacterial deposition in situ. Functional modification is not required to recognize the bacteria specifically in our designed dialyzer. Moreover, the microcavity interface clears over 95% bacteria from a fluid blood sample without inducing protein adsorption or complement and platelet activation when contacting the fluid blood. The study supports this biomimetic microcavity interface to be a promising extracorporeal blood-cleansing device in clinical settings.

Hypoxia-responsive nanogel as IL-12 carrier for anti-cancer therapy.

In the past two decades, protein drugs have evolved to become the most successful and important strategy in cancer therapy. However, systematical administration of protein drugs may cause serious side effects. In order to prepare a new promising hydrophilic drugs carrier, we constructed a PEGylated hyaluronic acid nanogel (NI-MAHA-PEG nanogel) with hypoxia and enzymatic responsiveness, which can selectively release hydrophilic drugs interleukin-12 (IL-12) on demand in a tumor microenvironment. We observed that release of IL-12 from nanogels by hypoxia-responsive stimulation, nanogels have anti-tumor effects on melanoma. Compared with physiological conditions, the IL-12 release rate has achieved remarkable growth under hypoxic conditions. Similarly, the drug release rate increased significantly with the addition of 500 U ml-1 hyaluronidase. We provide a novel strategy to allow efficient delivery, on-demand release, and enhanced access of proteins to hypoxic tumor regions. The rational design of this nanogels drug delivery system can further explore the use of various drugs to treat many cancers.

Stable Li Metal Anodes via Regulating Lithium Plating/Stripping in Vertically Aligned Microchannels.

Li anodes have been rapidly developed in recent years owing to the rising demand for higher-energy-density batteries. However, the safety issues induced by dendrites hinder the practical applications of Li anodes. Here, Li metal anodes stabilized by regulating lithium plating/stripping in vertically aligned microchannels are reported. The current density distribution and morphology evolution of the Li deposits on porous Cu current collectors are systematically analyzed. Based on simulations in COMSOL Multiphysics, the tip effect leads to preferential deposition on the microchannel walls, thus taking full advantage of the lightening rod theory of classical electromagnetism for restraining growth of Li dendrites. The Li anode with a porous Cu current collector achieves an enhanced cycle stability and a higher average Coulombic efficiency of 98.5% within 200 cycles. In addition, the resultant LiFePO4 /Li full battery demonstrates excellent rate capability and stable cycling performance, thus demonstrating promise as a current collector for high-energy-density, safe rechargeable Li batteries.

Passivation of Lithium Metal Anode via Hybrid Ionic Liquid Electrolyte toward Stable Li Plating/Stripping.

Hybrid electrolyte of ionic liquid and ethers is used to passivate the surface of Li metal surface via modification of the as-formed solid electrolyte interphase with N-propyl-N-methylpyrrolidinium bis(trifluoromethanesulfonyl)amide (Py13TFSI), thereby reducing the side reactions between the Li metal and electrolyte, leading to remarkably suppressed Li dendrite growth and mitigating Li metal corrosion.