Nematic Fibrin Fibers Enabling Vascularized Thrombus Implants Facilitate Scarless Cutaneous Wound Healing.

Autologous implantable scaffolds that induce vasculogenesis have shown great potential in tissue regeneration; however, previous attempts mainly relied on cell-laden hydrogel patches using fat tissues or platelet-rich plasma, which are insufficient for generating a uniform vasculature in a scalable manner. Here, implantable vascularized engineered thrombi (IVETs) are presented using autologous whole blood, which potentiate effective skin wound healing by constructing robust microcapillary vessel networks at the wound site. Microfluidic shear stresses enable the alignment of bundled fibrin fibers along the direction of the blood flow streamlines and the activation of platelets, both of which offer moderate stiffness of the microenvironment optimal for facilitating endothelial cell maturation and vascularization. Rodent dorsal skin wounds patched with IVET present superior wound closure rates (96.08 ± 1.58%), epidermis thickness, collagen deposition, hair follicle numbers, and neutrophil infiltration, which are permitted by enhanced microvascular circulation. Moreover, IVET treatment accelerates wound healing by recruiting M2 phenotype macrophages.

Robust chemical bonding of PMMA microfluidic devices to porous PETE membranes for reliable cytotoxicity testing of drugs.

Here, we report a simple yet reliable method for bonding poly(methyl methacrylate) (PMMA) to polyethylene terephthalate (PETE) track-etched membranes using (3-glycidyloxypropyl)trimethoxysilane (GLYMO), which enables reliable cytotoxicity tests in a microfluidic device impermeable to small molecules, such as anti-cancer drugs. The porous PETE membranes treated with 5% GLYMO were assembled with microfluidic channel-engraved PMMA substrates after air plasma treatment for 1 minute, followed by heating at 100 °C for 2 minutes, which permits irreversible and complete bonding to be achieved within 1 h. The bonding strength between the two substrates (1.97 × 107 kg m-2) was robust enough to flow culture medium through the device without leakage even at a gauge pressure of above 135 kPa. For validation of its utility in drugs testing, we successfully demonstrated that human lung adenocarcinoma cells cultured in the PMMA devices show more reliable cytotoxicity results for vincristine in comparison to conventional polydimethylsiloxane (PDMS) devices due to the inherent property of PMMA of it being impervious to small molecules. Given that the current organ-on-a-chip fabrication methods mostly rely on PDMS, this bonding strategy will expand simple fabrication capability using various thermoplastics and porous track-etched membranes, and allow us to create 3D-micro-constructs that more precisely mimic organ-level physiological conditions.

Preparation of beta-tricalcium phosphate microsphere-hyaluronic acid-based powder gel composite as a carrier for rhBMP-2 injection and evaluation using long bone segmental defect model.

The specific objective of this study was to evaluate whether rhBMP-2-loaded bio-scaffolds can be used as effective rhBMP-2 carriers in the implantation of bone defect sites or poor bone quality in host bone. The rhBMP-2 release pattern test showed slow results in both groups, and a 1:9 ratio composition with a high water-absorption rate was selected for in vivo study. All animals euthanized after 9 weeks. The new bone formation and bone quantity and quality of fibular samples were examined. The results showed that the rhBMP-2 powder gel composite improved the new bone formation in the cortical bone and the marrow space. The length of new bone formation ratio of the rhBMP-2 loaded composite group was significantly higher than the powder gel group. The composite of powder gel seems to be a nice carrier, and slow release of rhBMP-2 can promote new bone formation in a segmental cortical bone defect after implantation.

Advection Flows-Enhanced Magnetic Separation for High-Throughput Bacteria Separation from Undiluted Whole Blood.

A major challenge to scale up a microfluidic magnetic separator for extracorporeal blood cleansing applications is to overcome low magnetic drag velocity caused by viscous blood components interfering with magnetophoresis. Therefore, there is an unmet need to develop an effective method to position magnetic particles to the area of augmented magnetic flux density gradients while retaining clinically applicable throughput. Here, a magnetophoretic cell separation device, integrated with slanted ridge-arrays in a microfluidic channel, is reported. The slanted ridges patterned in the microfluidic channels generate spiral flows along the microfluidic channel. The cells bound with magnetic particles follow trajectories of the spiral streamlines and are repeatedly transferred in a transverse direction toward the area adjacent to a ferromagnetic nickel structure, where they are exposed to a highly augmented magnetic force of 7.68 µN that is much greater than the force (0.35 pN) at the side of the channel furthest from the nickel structure. With this approach, 91.68% ± 2.18% of Escherichia coli (E. coli) bound with magnetic nanoparticles are successfully separated from undiluted whole blood at a flow rate of 0.6 mL h-1 in a single microfluidic channel, whereas only 23.98% ± 6.59% of E. coli are depleted in the conventional microfluidic device.

Discovery of hybrid Hsp90 inhibitors and their anti-neoplastic effects against gefitinib-resistant non-small cell lung cancer (NSCLC).

Heat shock protein 90 (Hsp90) represents an attractive cancer therapeutic target due to its role in the stabilization and maturation of many oncogenic proteins. We have designed a series of hybrid Hsp90 inhibitors by connecting the resorcinol ring of VER-49009 (2) and the trimethoxyphenyl ring of PU3 (3) using structure-based approach. Subsequent testing established that compound 1f inhibited gefitinib-resistant H1975 cell proliferation, brought about the degradation of Hsp90 client proteins including EGFR, Met, Her2 and Akt and induced the expression of Hsp70. The design, synthesis, and evaluation of 1f are described herein.

Anti-aging effect of rice wine in cultured human fibroblasts and keratinocytes.

The application of rice wine on skin is known to have beneficial effects such as enhancement of the skin barrier function and skin whitening. In this study, we focused on examination of the anti-aging effects of rice wine. The treatment of fibroblasts with rice wine in vitro increased the expression of procollagen and laminin-5, a key basement membrane component in cultured human fibroblasts. Rice wine significantly reduced the expression of UV-induced matrix metalloproteinase-1 (MMP-1) in a dose-dependent manner in both cultured human fibroblasts and keratinocytes. In addition, treatment with rice wine decreased UV-induced tumor necrosis factor-alpha (TNF-alpha) production in human keratinocytes. An in vivo study using hairless mice showed that topical application of rice wine protected mouse skin from photoaging. Thus, we suggest that rice wine may have potential as an effective agent for the prevention and treatment of UV-induced skin aging.