Advanced Nanobiomed Research最新文献

Digital Microfluidics

In article 2400044, Nam-Trung Nguyen and co-workers introduce liquid beads, liquid sample encapsulated in a solid shell, for sample partitioning of digital loop-mediated isothermal amplification (dLAMP). Accurate and reproducible the quantitative detection of a gene cluster of leaf scald disease was conducted using this dLAMP approach. The results demonstrate the robust performance of this technique as compared to droplet-based and conventional quantitative approaches.

Optical-Biosensors

ZnO nanostructure-based biosensors detect enteropathogenic Escherichia coli in real-time (5–10 sec), with optical responses varying by bacterial concentration, distinguishing between viable and lysed cells. More details can be found in article 2400013 by Ateet Dutt and co-workers.

Nanoarchitectonics, as a post-nanotechnology concept, represents a methodology for the construction of functional materials employing atoms, molecules, and nanomaterials as essential components. The overarching objective of nanoarchitectonics is to develop functional systems comprising multiple functional units assembled in a hierarchical manner, as observed in biological systems. Nevertheless, the construction of such functional systems is a challenging endeavor. It would be prudent, therefore, to initially focus on the development of functional materials that interact with the complex functional structures of living organisms. Accordingly, this review article addresses the topic of nanoarchitecture as it pertains to biomedical applications. This article examines the current trends in research and presents examples of studies that support the concept of nanoarchitectonics and its applications in biomedical fields. The examples presented are as follows: i) molecular nanoarchitectonics developments, which are mainly based on molecular design and assembly; ii) material nanoarchitectonics examples, which are mainly based on material design using nanomaterials as components; and iii) biomedical applications with porous materials, which will be summarized under the heading of pore-engineered nanoarchitectonics due to their special structure. Finally, the review provides an overview of these examples and discusses future prospects.

The controlled delivery of selenium nanoparticles (Se-NPs) is promising for bone cancer treatment due to their dual benefits in bone regeneration and tumor inhibition, yet achieving an optimal dosing regimen remains challenging. Natural mesoporous biosilica (BS) beads have shown promise for drug delivery due to their microporous structure. This study explores incorporating BS beads into collagen-chitosan (Coll-CS) scaffolds, known for bone repair, to control Se-NP delivery. Two approaches are compared: loading Se-NPs into BS beads before integrating them into Coll-CS scaffolds versus directly loading Se-NPs into Coll-CS scaffolds. The scaffold properties, Se release kinetics, cytocompatibility, and effects on mesenchymal stem cells (MSCs) and prostate cancer cells (LNCaP) are evaluated. BS bead-loaded scaffolds provide controlled Se-NP release and enhanced mechanical properties compared to directly loaded scaffolds. Higher Se-NP concentrations in BS-loaded scaffolds effectively promote MSC osteogenic differentiation and mineralisation while inhibiting LNCaP cell viability. In contrast, low Se-NP concentrations not only induce early osteogenic differentiation but also promote cancer cell proliferation, underscoring the need for optimal Se-NP concentration and release. These findings suggest that BS bead-loaded Coll-CS scaffolds are a promising strategy for controlled Se-NP delivery, addressing the dual challenges of bone formation and cancer recurrence prevention in bone cancer treatment.

Osteoarthritis (OA) is characterized mainly by articular cartilage loss, subchondral osteosclerosis, and chronic inflammation and involves multiple types of cellular dysfunction and tissue lesions. The rapid development of nanotechnology and materials science has contributed to the application of biomimetic nanomaterials in the biomedical field. By optimizing the composition, hardness, porosity, and drug loading of biomimetic nanomaterials, their unique physicochemical properties drive potential applications in bone repair. This article reviews the present understanding of the physiopathological mechanism and clinical treatment drawbacks of OA and summarizes various types of biomimetic nanomaterials for OA that target lesion sites, such as cartilage, subchondral bone, and synovium, through simulation of the physiological structure and microenvironment. Eventually, the challenges and prospects for the clinical translation of biomimetic nanomaterials are further discussed, with the goal of accessing an effective approach for OA treatment.

Architectural, compositional, and mechanical gradients are present in many interfacial tissues in the body. Yet desired for regeneration, the recreation of these complex natural gradients in porous scaffolds remains a challenging task. Additive manufacturing (AM) has been highlighted as a technology to fabricate constructs to regenerate interfacial tissues. Integration of different types of gradients, which can be physical, mechanical, and/or biochemical, shows promise to control cell fate and the regeneration process in a spatial controlled manner. One of the most studied tissue interfaces is the osteochondral unit which connects cartilage to bone. This tissue is often damaged because of trauma or ageing, leading to osteoarthritis; a degenerative disease and a major cause of disability worldwide. Therefore, in view of osteochondral (OC) regeneration, a state-of-the-art overview of current approaches is presented to manufacture gradient scaffolds prepared by AM techniques. The focus is on thermoplastic, hydrogel, and hybrid scaffolds comprising gradients that induce biomimicry by their physical and biological properties. The effect of these different systems on OC tissue formation in-vitro and in-vivo is addressed. Finally, an outlook on current trends of dynamic materials is provided, including proposals on how these materials could improve the mimicry of scaffolds applied for OC regeneration.

Digital nucleic acid analysis has emerged as a prominent tool for the detection and absolute quantification of diverse pathogens. Digital loop-mediated isothermal amplification (dLAMP) offers highly sensitive, specific, time-efficient, and cost-effective nucleic acid amplification. However, existing dLAMP techniques face challenges such as droplet merging, reliance on surfactants, restricted partition capacities, and the potential for sample loss during heating. Herein, these issues are addressed by introducing liquid beads for sample partitioning. Compared to microwells, our approach overcomes the limitations of chamber dimensions, enabling the analysis of an unlimited number of digitized targets. Furthermore, our novel approach effectively addresses sample loss and merging during thermal processing and eliminates the need for surfactants. Accurate and reproducible the quantitative detection of the gene cluster XALB1 of leaf scald disease is conducted using dLAMP based on liquid beads to verify its availability. The results demonstrate a high correlation between target concentration and positive signals, indicating the robust performance of our technique. A comparative analysis is then performed between dLAMP using liquid beads and using single droplets. Benchmarking these two techniques highlights the effectiveness of our innovative technique in overcoming existing challenges in dLAMP.

Mesenchymal stem cell (MSC) therapy aids cardiac repair and regeneration, but the low rate of MSC survival and engulfment in the infarcted heart remains a major obstacle for routine clinical application. Here, an injectable suspension of human acellular amniotic membrane (HAAM) that may serve as synergistic cell delivery vehicle for the treatment of myocardial infarction (MI) by improving MSC homing and survival is developed. The results demonstrate that compared with MSC transplantation alone, HAAM-loaded MSCs have higher survival and engraftment rates in infarcted tissue, alleviated hypoxia-induced myocardial damage, achieved higher improvements in cardiac function, promoted angiogenesis, and reduced myocardial fibrosis. In addition, HAAM-loaded MSCs increase N-cadherin levels and thereby enhance the efficacy of MSCs in treating MI. This study provides a new approach for MSC-based cardiac repair and regeneration.

Extracellular vesicles (EVs) are gaining interest in regenerative medicine and biomaterials have been shown to extend EV bioavailability following delivery. Herein, the labeling of both hydrogels and EVs is reported to better understand hydrogel design for sustained EV release into tissues. Shear-thinning hydrogels are engineered using guest–host (i.e., adamantane–cyclodextrin) modifications to hyaluronic acid (GH), as well as GH hydrogels with the addition of gelatin crosslinked via transglutaminase (GH+Gel) to temporally control hydrogel properties. When labeled with a near-IR dye and injected into rat myocardial tissue, the GH+Gel hydrogel is retained (>14 days) longer than the GH hydrogel alone (≈7 days), likely due to the added gelatin network. To overcome challenges associated with common EV labeling methods, a highly versatile metabolic labeling methodology is utilized via the incorporation of N-azidoacetylmannosamine-tetraacylated during EV synthesis to introduce azide groups that can then be reacted with DBCO dyes. When injected in saline, EVs are cleared within 24 h in hearts; however, hydrogels enhance EV retention, with levels based on hydrogel degradation behavior, namely, >14 days for GH+Gel hydrogel and ≈7 days for GH hydrogel alone. These findings support the use of hydrogels in EV therapies.

Verteporfin (VP) has been used for photodynamic therapy (PDT) for over 20 years, and new applications have brought it back into the spotlight. VP is hydrophobic and requires lipid carriers for clinical delivery as Visudyne. A nanosuspension of VP, termed NanoVP, that requires no carriers is developed, permitting delivery of VP alone in an aqueous solution. NanoVP is produced by solvent–antisolvent precipitation, with dimethyl sulfoxide as the preferable solvent of several screened. The initial formulation has a hydrodynamic diameter of 104 ± 6.0 nm, concentration of 133 ± 10 μm, polydispersity index (Pdi) of 0.12 ± 0.01, and zeta potential of −22.0 ± 0.93 mV. Seeking a concentration >500 μm, a zeta potential <−10 mV, a diameter <64 nm, and a Pdi < 0.2, eight synthesis parameters are probed, identifying three that modified nanoparticle diameter and three that modified nanoparticle dispersity. The diameter is tuned fourfold from 49.0 ± 4.4 to 195 ± 7.1 nm, and the solution concentration is increased by 6.3-fold to 838 ± 45.0 μm. Finally, the bioavailability and anticancer capacity of NanoVP in glioblastoma are evaluated. In all, this provides a framework for the modification of amorphous nanoparticle properties and a new formulation for clinical use of VP.