Pathogenic infection inevitably provokes chronic inflammation and stalls the normal orchestrated course of wound-healing cascades. However, current antibacterial therapies focus on the inherent bactericidal functions of biomaterials. To take full advantage of infection microenvironment (IME) peculiarities, an IME-activated nanocatalytic membrane consisting of electrospun poly (lacticco-glycolic acid) (PLGA) scaffolds, MXene/Ag 2 S bio-heterojunctions (MX/ AS bio-HJs), and lactate oxidase (LOx) for chronic cutaneous regeneration is devised and developed. In this "intelligent" system, PLGA membranes gradually degrade to lactate, and LOx consumes lactate to yield abundant hydrogen peroxide (H 2 O 2 ) in a microenvironment-responsive manner. In addition, MX/ AS bio-HJs in membranes not only exert benign photothermal effects and generate reactive oxygen species upon NIR light, but also catalyze the produced H 2 O 2 to overwhelming hydroxyl radicals (•OH) through Fenton-like reactions, which all result in rapid synergistic sterilization. Furthermore, in vivo assays demonstrate that the nanocatalytic membranes reshape the stalled chronic wound into a regenerative wound by massacring bacteria, stopping bleeding, boosting epithelialization/collagen deposition of the wound beds, and promoting angiogenesis. As envisaged, the proposed tactic opens up a promising opportunity for arming membranes with IME-responsive nanocatalytic activity to remedy bacteria-invaded stalled full-thickness wounds.
Infection and malignant tumors are the most common diseases in people's daily life, which seriously threaten human health. Because of the frequent and extensive administration of antibiotics and chemodrugs, the prevalence of multidrug-resistant bacteria and tumor cells makes the conventional therapies less effective and even invalid. To overcome the repugnant dilemma, herein the authors devise and develop a hollow Cu 2−X S nano-homojunction (nano-HJ) platform for the effective eradication of both bacteria and tumors upon tissue-penetrable near-infrared (NIR) light irradiation. Hyaluronan (HA) is covalently decorated onto the nano-homojunctions (nano-HJs) surface to enhance their biocompatibility, tumor-targeting ability, and cutaneous wound healing capability. The decorated nano-HJs exert robust NIR-activatable bactericidal modality and accelerate the cutaneous regeneration of bacteria-invaded full-thickness wounds through the synergy of photothermal/photodynamic effects, glutathione depletion, and HA assistance. After loading anticancer drug doxorubicin in the cavity of nano-HJs, the antitumor therapy efficacy is greatly strengthened both in vitro and in vivo by the collaborative photochemotherapy. Accordingly, this work not only highlights the great promise of the Cu 2−X S nano-HJs in the treatment of bacteria-induced contagious diseases and malignant tumors but also opens up a new research direction for the biomedical application of homojunction nanoplatforms in the future.
For quick disinfection treatment, phototherapy, including photothermal therapy and photodynamic therapy, has emerged as a promising alternative to conventional methods. However, the bactericidal effect of phototherapy, which only works upon light, is short‐lived. The remaining bacteria in situ may repopulate when the irradiation of light is withdrawn. To address this refractory concern, an antibacterial fibrous membrane consisting of electrospun poly (polycaprolactone) scaffolds and polydopamine (pDA) coated MXene/Ag3PO4 bioheterojunctions (MX@AgP bio‐HJs) is devised and developed. Upon near‐infrared (NIR) illumination, the MX@AgP nanoparticle (NP) in nanofibrous electrospun membranes exert the excellent bactericidal effect of phototherapy and release Ag+ ions which stop the remaining bacteria from multiplying in the dark state. When removing NIR light, pDA in situ reduces Ag+ ions to Ag0 NPs to realize the self‐rechargeability of Ag+ ions and provides enough Ag+ ions for the second phototherapy. In vivo results show that photoactivated nanofibrous membranes can re‐shape an infected wound microenvironment to the regenerative microenvironment through killing bacteria, ceasing bleeding, increasing epithelialization, and collagen deposition on the wound bed, as well as promoting angiogenesis. As predicted, the proposal work offers potential prospects for nanofibrous membranes with NIR‐assisted “self‐rechargeable” antibacterial properties to treat bacteria‐infected full‐thickness wounds.
Subthreshold amplifiers suffer from the limited voltage headroom which leaves little space for conventional analog techniques to enhance performance and efficiency. This paper presents an evolution process of implementing conventional structures with inverters, allowing ultralow-voltage operation with increased flexibility in adopting traditional circuit techniques. Based on the proposed inverter-based elementary structure and CMFB, both the Miller-compensated (MC) operational transconductance amplifier (OTA) and the feedforward-compensated (FFC) OTA achieve significantly improved performance as compared to previous works. The proposed amplifier techniques are verified in modulator (DSM) design, with MC-OTA for a DT-DSM and FFC-OTA for a CT-DSM, both fabricated in a 0.13-μm CMOS. The 0.3-V DT-DSM achieves 74.1-dB SNDR, 83.4-dB SFDR and 20-kHz bandwidth with 79.3-μW power, resulting in a Schreier figure of merit (FoM) of 158 dB. The 0.3-V CT-DSM achieves 68.5-dB SNDR, 82.6-dB SFDR, and 50-kHz bandwidth with 26.3-μW power, leading to a Schreier FoM of 161 dB. Both DSMs exhibit highly competitive performance among sub-0.5-V designs, validating the proposed subthreshold amplifier techniques.
Combination therapy has gained a lot of attention thanks to its superior activity against cancer. In the present study, we report a cRGDtargeted liposomal preparation for co-delivery of programmed cell death ligand 1 (PD-L1) small interfering RNA (siRNA) and anemoside B4 (AB4)AB4/siP-c-Land evaluate its anticancer efficiency in mouse models of LLC and 4T1 tumors. AB4/siP-c-L showed a particle size of (180.7 ± 7.3) nm and a ζ-potential of (32.8 ± 1.5) mV, with high drug encapsulation, pH-sensitive release properties, and good stability in serum. AB4/siP-c-L demonstrated prolonged blood circulation and increased tumor accumulation. Elevated cellular uptake was dependent on the targeting ligand cRGD. This combination induced significant tumor inhibition in LLC xenograft tumor-bearing mice by downregulating PD-L1 protein expression and modulating the immunosuppressive microenvironment. Liposomes favored the antitumor T-cell response with long-term memory, without obvious toxicity. A similar tumor growth inhibition was also demonstrated in the 4T1 tumor model. In summary, our results indicate that cRGD-modified and AB4and PD-L1 siRNA-coloaded liposomes have potential as an antitumor preparation, and this approach may lay a foundation for the development of a new targeted drug delivery system.
Clinical application of the amniotic
membrane (AM) in vascular
reconstruction was limited by poor processability, rapid biodegradation,
and insufficient hemocompatibility. In this work, decellularized AM
was digested to a thermosensitive hydrogel and densely cross-linked
in the nanoscale as “enhanced” collagenous fibers. Via N-(3-dimehylaminopropyl)-N′-ethylcarbodiimide
and N-hydroxysuccinimide (EDC/NHS) catalysis, REDV
was further grafted to simulate anticoagulant substances on naturally
derived blood vessels. This modification approach endowed AM with
rapid endothelialization and rare vascular restenosis. Through adjusting
the fixation condition, the pore size and mechanical stability of
the fiber network were approximate to those of natural tissues and
precisely designed to fit for cell adhesion. AM was synchronously
fixed by alginate dialdehyde (ADA) and EDC/NHS, forming a “double-cross-linked”
stable structure with significantly improved mechanical strength and
resistance against enzymic degradation. The hemolytic and platelet
adhesion test indicated that ADA/REDV-AM could inhibit hemolysis and
coagulation. It also exhibited excellent cytocompatibility. It selectively
accelerated adsorption and migration of endothelial cells (ECs) while
impeding adhesion and proliferation of smooth muscle cells (SMCs).
It maintained EC superiority in competitive growth and avoided thrombosis
in vivo. Furthermore, its property of promoting reconstruction and
repair of blood vessels was proved in an animal experiment. Overall,
the present study demonstrates that ADA/REDV-AM has potential application
as a small-diameter artificial vascular intima with rapid endothelialization
and reduced SMC/platelet adhesion.
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