Multifunctional nanoparticles are increasingly employed to improve biological efficiency in medical imaging, diagnostics, and treatment applications. However, even the most well-established nanoparticle platforms rely on multiple-step wet-chemistry approaches for functionalization often with linkers, substantially increasing complexity and cost, while limiting efficacy. Plasma dust nanoparticles are ubiquitous in space, commonly observed in reactive plasmas, and long regarded as detrimental to many manufacturing processes. As the bulk of research to date has sought to eliminate plasma nanoparticles, their potential in theranostics has been overlooked. Here we show that carbon-activated plasma-polymerized nanoparticles (nanoP 3 ) can be synthesized in dusty plasmas with tailored properties, in a process that is compatible with scale up to high throughput, low-cost commercial production. We demonstrate that nanoP 3 have a long active shelf life, containing a reservoir of long-lived radicals embedded during their synthesis that facilitate attachment of molecules upon contact with the nanoparticle surface. Following synthesis, nanoP 3 are transferred to the bench, where simple one-step incubation in aqueous solution, without the need for intermediate chemical linkers or purification steps, immobilizes multiple cargo that retain biological activity. Bare nanoP 3 readily enter multiple cell types and do not inhibit cell proliferation. Following functionalization with multiple fluorescently labeled cargo, nanoP 3 retain their ability to cross the cell membrane. This paper shows the unanticipated potential of carbonaceous plasma dust for theranostics, facilitating simultaneous imaging and cargo delivery on an easily customizable, functionalizable, cost-effective, and scalable nanoparticle platform.
Current synthetic vascular grafts are not suitable for use in low-diameter applications. Silk fibroin is a promising natural graft material which may be an effective alternative. In this study, we compared two electrospun silk grafts with different manufacturing processes, using either water or hexafluoroisopropanol (HFIP) as solvent. This resulted in markedly different Young’s modulus, ultimate tensile strength and burst pressure, with HFIP spun grafts observed to have thicker fibres, and greater stiffness and strength relative to water spun. Assessment in a rat abdominal aorta grafting model showed significantly faster endothelialisation of the HFIP spun graft relative to water spun. Neointimal hyperplasia in the HFIP graft also stabilised significantly earlier, correlated with an earlier SMC phenotype switch from synthetic to contractile, increasing extracellular matrix protein density. An initial examination of the macrophage response showed that HFIP spun conduits promoted an anti-inflammatory M2 phenotype at early timepoints while reducing the pro-inflammatory M1 phenotype relative to water spun grafts. These observations demonstrate the important role of the manufacturing process and physical graft properties in determining the physiological response. Our study is the first to comprehensively study these differences for silk in a long-term rodent model.
Visual AbstractElectrospinning of silk to create nanofibers, which deposit onto a rotating collector. This results in the formation of a pure silk conduit of 1.5 mm internal diameter. These conduits are then implanted into the descending abdominal aorta of Sprague Dawley Rats with end-to-end suturing, and left for 3, 6, 12, and 24 weeks. Endpoint histologic analysis of the explanted grafts demonstrate hyperplasia stabilization, complete endothelialization and excellent blood compatibility.
The long-term performance of many medical implants is limited by the use of inherently incompatible and bioinert materials. Metallic alloys, ceramics, and polymers commonly used in cardiovascular devices encourage clot formation and fail to promote the appropriate molecular signaling required for complete implant integration. Surface coating strategies have been proposed for these materials, but coronary stents are particularly problematic as the large surface deformations they experience in deployment require a mechanically robust coating interface. Here, we demonstrate a single-step ion-assisted plasma deposition process to tailor plasma-activated interfaces to meet current clinical demands for vascular implants. Using a process control-feedback strategy which predicts crucial coating growth mechanisms by adopting a suitable macroscopic plasma description in combination with noninvasive plasma diagnostics, we describe the optimal conditions to generate highly reproducible, industry-scalable stent coatings. These interfaces are mechanically robust, resisting delamination even upon plastic deformation of the underlying material, and were developed in consideration of the need for hemocompatibility and the capacity for biomolecule immobilization. Our optimized coating conditions combine the best mechanical properties with strong covalent attachment capacity and excellent blood compatibility in initial testing with plasma and whole blood, demonstrating the potential for improved vascular stent coatings.
β 3 -peptides uniquely form shear thinning hydrogels which are proteolytically stable and biocompatible. Herein we describe the synthesis, material and optical characterization of a new class of fluorescently labeled hydrogelators based on a helical N-acetylated β 3 -peptide backbone. The resulting hydrogels were analyzed using fluorescence microscopy to confirm successful incorporation of the fluorophore within the fiber matrix without compromising the β 3 -peptide self-assembly. Serial, noninvasive conscious animal imaging was used to monitor the injected hydrogel, delivered via subcutaneous injection, while tracking their degradation patterns in real-time. The hydrogels demonstrated persistent, high-intensity fluorescence when monitored over a 14-day period.
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