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Physical-property-based patterning is an alternative biofabrication approach that relies on the application of a remote field, and the intrinsic properties of the objects or materials of interest, to simply create complex tissues. Both buoyant and gravitational forces can rapidly create tissue gradients without any hardware, highlighting the appeal of in situ density-based patterning. Recent advances now allow for the magnetic patterning of naturally diamagnetic cells using paramagnetic solutions, including crosslinkable hydrogels. New methods have been developed to change the compressibility of a cell, enabling differential cell separation and alignment within an acoustic field. The field of biofabrication is rapidly expanding with the advent of new technologies and material systems to engineer complex tissues. In this opinion article, we introduce an emerging tissue patterning method, physical-property-based patterning, that has strong translational potential given its simplicity and limited dependence on external hardware. Physical-property-based patterning relies solely on the intrinsic density, magnetic susceptibility, or compressibility of an object, its surrounding solution, and the noncontact application of a remote field. We discuss how physical properties can be exploited to pattern objects and design a variety of biologic tissues. Finally, we pose several open questions that, if addressed, could transform the status quo of biofabrication, pushing us one step closer to patterning tissues in situ. [ABSTRACT FROM AUTHOR]

Great strides have been taken towards the in vitro engineering of clinically relevant tissue constructs using the classic triad of cells, materials, and biochemical factors. In this perspective, we highlight ways in which these elements can be manipulated or stimulated using a fourth component: the application of remote fields. This arena has gained great momentum over the last few years, with a recent surge of interest in using magnetic, optical, and acoustic fields to guide the organization of cells, materials, and biochemical factors. We summarize recent developments and trends in this arena and then lay out a series of challenges that we believe, if met, could enable the widespread adoption of remote fields in mainstream tissue engineering. Remote fields have recently emerged as an alternative to contact force application and microfabrication in the engineering of complex tissue structures. New methods have been developed that use magnetic fields to manipulate nanoparticles for biochemical patterning, material assembly, and biological actuation. A series of recent reports in optical manipulation have shown high-level control over gene expression, epigenetics, material degradation, and reversible protein immobilization. Recent advances have been made in preserving acoustically patterned cell arrays, which have enabled the engineering skeletal muscle, cardiac, and neural tissue. [ABSTRACT FROM AUTHOR]

Age‐ or length‐structured stock assessments require reliable life history demographic parameters (growth, mortality, reproduction) to model population dynamics, potential yields and stock sustainability. This study synthesized life history information for 84 commercially exploited tropical reef fish species from Florida and the U.S. Caribbean (Puerto Rico and the U.S. Virgin Islands). We attempted to identify a useable set of life history parameters for each species that included lifespan, length at age, weight at length and maturity at length. Key aspects of the life history synthesis were development of: (a) a database that characterized study details including sampling region, biological and statistical methods, length range of sampled individuals, sample size, capture gears and sampling time frame; (b) reproducible procedural criteria for parameter identification for a given species; and (c) a reliability metric for each parameter type. Complete life history parameter sets were available for 46 species analysed. Of these, only 16 species had parameter sets meeting the highest standards for reliability, highlighting future research needs. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs), sub-micron vectors used in intercellular communication, have demonstrated great promise as natural drug delivery systems. Recent reports have detailed impressive in vivo results from the administration of EVs pre-loaded with therapeutic cargo, including small molecules, nanoparticles, proteins and oligonucleotides. These results have sparked intensive research interest across a huge range of disease models. There are, however, enduring limitations that have restricted widespread clinical and pharmaceutical adoption. In this perspective, we discuss these practical and biological concerns, critically compare the relative merit of EVs and synthetic drug delivery systems, and highlight the need for a more comprehensive understanding of in vivo transport and delivery. Within this framework, we seek to establish key areas in which EVs can gain a competitive advantage in order to provide the tangible added value required for widespread translation. [ABSTRACT FROM AUTHOR]

The article presents the discussion on self-assembly of nanofibers facilitating the repair of spinal cord injury in mice. Topics include design of materials for encouraging the repair of tissue after injury being a longstanding goal of regenerative medicine; tuning the dynamics of bioactive supramolecular polymers correlating with the degree of regeneration and functional outcome; and comparing with many covalent polymers displaying high epitope density.

A highly sensitive label-free assay for the determination of blood coagulation Factor XIII activity is demonstrated through the controlled assembly of peptide-functionalized gold nanoparticles (AuNPs). Activated Factor XIII catalyzes the formation of covalent crosslinking between peptide chains through ε-(γ-glutamyl)-lysine bonds leading to the aggregation of the AuNPs and consequently a red-shift of the localized surface plasmon resonance. The selective engineering of nanoscale order over AuNP crosslinking via the formation of isopeptide bonds provides a new approach toward the design of nanoassemblies with precise control on the molecular level. The colorimetric assay reported here provides direct qualitative and quantitative analysis of Factor XIII activity with a limit of detection of 0.01 U mL-1. [ABSTRACT FROM AUTHOR]

In resource-constrained countries, affordable methodologies for the detection of disease biomarkers at ultralow concentrations can potentially improve the standard of living. However, current strategies for ultrasensitive detection often require sophisticated instruments that may not be available in laboratories with fewer resources. Here, we circumvent this problem by introducing a signal generation mechanism for biosensing that enables the detection of a few molecules of analyte with the naked eye. The enzyme label of an enzyme-linked immunosorbent assay (ELISA) controls the growth of gold nanoparticles and generates coloured solutions with distinct tonality when the analyte is present. Prostate specific antigen (PSA) and HIV-1 capsid antigen p24 were detected in whole serum at the ultralow concentration of 1 × 10−18 g ml−1. p24 was also detected with the naked eye in the sera of HIV-infected patients showing viral loads undetectable by a gold standard nucleic acid-based test. [ABSTRACT FROM AUTHOR]

Abstract: Multi-walled carbon nanotube (MWCNT)/C/polystyrene (PS) composite materials were prepared by in situ polymerization of monomer in preformed MWCNT/C foams. MWCNT/C foams were preformed using polyurethane foam as template. The preformed MWCNT/C foams had a more continuous conductive structure than the carbon nanotube networks formed by free assembly in composites. The structure of the MWCNT/C foam network was characterized with scanning electron microscopy. The MWCNT/C/PS composites have an electric conductivity higher than 0.01S/cm for a filler loading of 1wt.%. Enhancement of thermal conductivity and mechanical properties by the preformed MWCNT/C foam were also observed. [Copyright &y& Elsevier]

Objective: We sought to assess the validity and short-term responsiveness of the Pediatric Quality of Life Inventory™ 4.0 Generic Core Scales (PedsQL™) for febrile illnesses evaluated in the pediatric emergency department (ED). Design: Prospective cohort study of children 2-18 years discharged after ED evaluation for fever (⩾ 38°C). Self-administered, parent-report of health-related quality of life (HRQOL) was assessed using the PedsQL™ Acute Version, a validated HRQOL instrument. HRQOL was measured on ED presentation and at 7-10 day follow-up. At follow-up, duration of fever, child functional impairment, missed daycare/school, and disrupted family unit functioning, were assessed. Results: Of 160 subjects enrolled, 97 (61%) completed the study; mean follow-up was 8.7 days. Mean total HRQOL score on ED presentation was 76.4; mean follow-up score was 86.3. Compared to subjects that returned to baseline, statistically significant differences in HRQOL were noted for those with prolonged fever, child functional impairment, and relapse. Significant correlation was observed between HRQOL at follow-up and days of daycare/school missed (r = - 0.35, p = .003) and days of family disruption (r = -0.43, p < .001). Mean change in HRQOL within subjects, from ED visit to follow-up, was +9.8 (95% CI: 5.6-14.6). Effect size was 0.53, indicating moderate responsiveness. Conclusion: The PedsQL™ appears to be a valid and responsive indicator of HRQOL for shortterm febrile illnesses evaluated in the ED. [ABSTRACT FROM AUTHOR]

Materials that enhance bone regeneration have a wealth of potential clinical applications from the treatment of nonunion fractures to spinal fusion. The use of porous material scaffolds from bioceramic and polymer components to support bone cell and tissue growth is a longstanding area of interest. Current challenges include the engineering of materials that can match both the mechanical and biological context of real bone tissue matrix and support the vascularization of large tissue constructs. Scaffolds with new levels of biofunctionality that attempt to recreate nanoscale topographical and biofactor cues from the extracellular environment are emerging as interesting candidate biomimetic materials. [Copyright &y& Elsevier]

Abstract: This paper describes simple, inexpensive, and potentially generic methodology for generating patterns of mammalian cells on porous scaffolds for tissue engineering using replica printing. Circular patterns (diameter: 200, 700, and 1000μm) of human osteoblasts were transferred directly from topographically patterned agarose stamps onto porous hydroxyapatite scaffolds or onto fibronectin-coated glass slides. The use of hydrogel stamps provided a “wet”, biocompatible surface and maintained the viability of cells adsorbed on stamps during the patterning process. Stamps inked once with suspensions of cells allowed the repeated patterning of substrates. Direct stamping of human osteoblasts (and, potentially other mammalian cells) can be used to control the size, spacing, and geometry of patterns of cells printed on porous tissue engineering substrates. This approach may find use in controlling the spatial invasion of scaffolds, promoting the hierarchical organization of cells, and in controlling cell–cell interactions as a step in preservation of phenotypes of cells. [Copyright &y& Elsevier]

Cells are inherently sensitive to local mesoscale, microscale, and nanoscale patterns of chemistry and topography. We review current approaches to control cell behavior through the nanoscale engineering of materials surfaces. Far-reaching implications are emerging for applications including medical implants, cell supports, and materials that can be used as instructive three-dimensional environments for tissue regeneration. [ABSTRACT FROM AUTHOR]

Treatment of large defects requires the harvest of fresh living bone from the iliac crest. Harvest of this limited supply of bone is accompanied by extreme pain and morbidity. This has prompted the exploration of other alternatives to generate new bone using traditional principles of tissue engineering, wherein harvested cells are combined with porous scaffolds and stimulated with exogenous mitogens and morphogens in vitro and/or in vivo. We now show that large volumes of bone can be engineered in a predictable manner, without the need for cell transplantation and growth factor administration. The crux of the approach lies in the deliberate creation and manipulation of an artificial space (bioreactor) between the tibia and the periosteum, a mesenchymal layer rich in pluripotent cells, in such a way that the body's healing mechanism is leveraged in the engineering of neotissue. Using the "in vivo bioreactor" in New Zealand White rabbits, we have engineered bone that is biomechanically identical to native bone. The neobone formation followed predominantly an intramembraneous path, with woven bone matrix subsequently maturing into fully mineralized compact bone exhibiting all of the histological markers and mechanical properties of native bone. We harvested the bone after 6 weeks and transplanted it into contralateral tibial defects, resulting in complete integration after 6 weeks with no apparent morbidity at the donor site. Furthermore, in a proof-of-principle study, we have shown that by inhibiting angiogenesis and promoting a more hypoxic environment within the "in vivo bioreactor space," cartilage formation can be exclusively promoted. [ABSTRACT FROM AUTHOR]

The use of periosteum as a cell source for the in vitro engineering of grafts for articular cartilage repair requires the development of methods to obtain high viable cell numbers in the early stages of culture. In this study, we demonstrate that the addition of a mitogen, fibroblast growth factor-2 (FGF-2), during the early stage of the in vitro culture of periosteum in the presence of transforming growth factor-β1 (TGF-β1), significantly enhances cell proliferation, which results in increased neo-cartilage formation at later stages. Periosteal explants were cultured in vitro within alginate or agarose based gels in the presence of either FGF-2 for the first week, TGF-β1 for the first 2 weeks, FGF-2 and TGF-β1 for the first week and first 2 weeks respectively, or no added factors. Consistent with previous studies, periosteum derived neo-chondrogenesis occurred only in the presence of TGF-β1. The neo-cartilage was found to contain cartilage specific proteoglycans and Type-II collagen as determined by safranin-O and immunohistochemical staining respectively. Further medium supplementation with FGF-2 stimulated early cell proliferation (>3 fold higher total DNA content per explant at day 10). This resulted in a marked increase in the size of the cultured explants and in the total area of the explant staining positive for safranin-O (from around 50% to 85%, (p<0.05)) after 6 weeks culture. The ability to generate significant quantities of neo-cartilage within a biocompatible and biodegradable matrix such as alginate, which lacks the immunogenicity of agarose, could open new pathways to utilizing such constructs in articular cartilage tissue engineering applications. [Copyright &y& Elsevier]

Periosteum has been promoted as a potential substrate for tissue engineering. Its principal virtues are that it has a source of pluripotential mesenchymal cells and chondrogenic growth factors located in the cambium layer, and it can serve as a template for directional evolution of neo-tissue. The clinical use and in vitro study of periosteum-derived neo-tissue has been limited by the level of surgical skill required for harvest. Precise surgical technique, task-specific experience, adequate volume of procedures, and general surgical expertise are required for optimal harvest using the traditional periosteal elevator method. This report describes an easily mastered technique that preserves viability while providing the harvest of relatively large amounts of periosteum. Skeletally mature New Zealand white rabbits (11 males/20 tibias; 4 females/8 tibias; approximate weight 3.5 kg) and one Yucatan miniature pig were used for harvest of periosteum from the tibia using the traditional periosteal elevator and the developed hydraulic elevation approach. Histologic examination of the periosteal explants obtained by the developed method showed preservation of the cambium layer containing the progenitor cells necessary for the generation of neo-cartilage. This technique provides a simple method of harvesting large segments (>5 cm × 1 cm) of periosteum in a single procedure and may facilitate better exploitation of periosteum in tissue engineering. [ABSTRACT FROM AUTHOR]

In this study, we have developed a rapid-curing alginate gel system and demonstrated its utility as a scaffold for periosteum-derived chondrogenesis for articular cartilage tissue engineering applications. A homogeneous mechanically stable gel was formulated by inducing gelation of a 2% (w/v) solution of a high G content alginate (65–75% G) with a 75 mm solution of CaCl2. The gel exhibited near-elastic behavior at low levels of deformation (15%, R2=0.996), Young''s modulus of 0.17±0.01 MPa, and rapid gelation kinetics (<1 min to completion). The in vitro cell culture of chondrocytes in the gel yielded alginate/cell constructs that lacked the continuous, interconnected collagen/proteoglycan network of hyaline cartilage. In addition, we have demonstrated that this gel system is capable of supporting periosteum-derived chondrogenesis. We observed that when whole-tissue explants of periosteum were cultured in vitro within the gel, after 6 weeks, significant quantities (>50%) of the total area of the periosteal explants was composed of cartilage that was hyaline-like in appearance and contained cartilage-specific proteoglycans and type-II collagen. It is envisioned that such explants could be transplanted or regenerated in vivo within the biodegradable alginate matrix for the treatment of partial or full-thickness defects in articular cartilage. Importantly, the injectable delivery of the gel could be used in filling complex defects in the articular surface via minimally invasive procedures. [Copyright &y& Elsevier]

Digital archives of personal memories are becoming increasingly technically feasible, but there remain significant interaction design challenges. In this paper, we present a research and design study of the Living Memory Box, a device and service to assist families in preserving memories in a variety of media forms. Through a series of ethnographic interviews, design activities and focus groups, we have developed recommendations for the design and development of future personal memory systems and appliances. These improvements must be considered by future researchers in the coordination of multiple disciplines toward successful holistic systems. [ABSTRACT FROM AUTHOR]

The abundance dynamics of short-lived marine species often exhibit large-amplitude fluctuations, potentially driven by unknown but important species interactions and environmental effects. These complex dynamics pose challenges in forecasting and establishing robust reference points. Here, we introduce an empirical dynamic modeling (EDM) framework using time-delay embeddings to recover unspecified species interactions and environmental effects, and use walk-forward simulations with varying harvest rates to estimate maximum sustainable yield (MSY). Firstly, we apply our framework to simulated data under various dynamics scenarios and demonstrate the statistical robustness of EDM-based MSY. Secondly, we apply our framework to abundance and catch time series (>30 years) of federally managed brown shrimp stocks in the US Gulf of Mexico. We identify nonlinear signals and achieve high prediction accuracy in the empirical dynamics of brown shrimp. Lastly, based on the EDM of brown shrimp dynamics, we obtain MSY for timely and effective management. Our results highlight the utility of EDM in deriving reference points for short-lived species, particularly in situations where stock abundance and catch dynamics are influenced by unobserved species interactions and environmental effects in a complex ecosystem. [ABSTRACT FROM AUTHOR]

To address our climate emergency, "we must rapidly, radically reshape society"—Johnson & Wilkinson, All We Can Save. In science, reshaping requires formidable technical (cloud, coding, reproducibility) and cultural shifts (mindsets, hybrid collaboration, inclusion). We are a group of cross‐government and academic scientists that are exploring better ways of working and not being too entrenched in our bureaucracies to do better science, support colleagues, and change the culture at our organizations. We share much‐needed success stories and action for what we can all do to reshape science as part of the Open Science movement and 2023 Year of Open Science. [ABSTRACT FROM AUTHOR]

To address our climate emergency, "we must rapidly, radically reshape society"—Johnson & Wilkinson, All We Can Save. In science, reshaping requires formidable technical (cloud, coding, reproducibility) and cultural shifts (mindsets, hybrid collaboration, inclusion). We are a group of cross‐government and academic scientists that are exploring better ways of working and not being too entrenched in our bureaucracies to do better science, support colleagues, and change the culture at our organizations. We share much‐needed success stories and action for what we can all do to reshape science as part of the Open Science movement and 2023 Year of Open Science. [ABSTRACT FROM AUTHOR]

Due to the variety of roles served by the cell membrane, its composition and structure are complex, making it difficult to study. Bioorthogonal reactions, such as the strain promoted azide‐alkyne cycloaddition (SPAAC), are powerful tools for exploring the function of biomolecules in their native environment but have been largely unexplored within the context of lipid bilayers. Here, we developed a new approach to study the SPAAC reaction in liposomal membranes using azide‐ and strained alkyne‐functionalized Förster resonance energy transfer (FRET) dye pairs. This study represents the first characterization of the SPAAC reaction between diffusing molecules inside liposomal membranes. Potential applications of this work include in situ bioorthogonal labeling of membrane proteins, improved understanding of membrane dynamics and fluidity, and the generation of new probes for biosensing assays. [ABSTRACT FROM AUTHOR]

Due to the variety of roles served by the cell membrane, its composition and structure are complex, making it difficult to study. Bioorthogonal reactions, such as the strain promoted azide‐alkyne cycloaddition (SPAAC), are powerful tools for exploring the function of biomolecules in their native environment but have been largely unexplored within the context of lipid bilayers. Here, we developed a new approach to study the SPAAC reaction in liposomal membranes using azide‐ and strained alkyne‐functionalized Förster resonance energy transfer (FRET) dye pairs. This study represents the first characterization of the SPAAC reaction between diffusing molecules inside liposomal membranes. Potential applications of this work include in situ bioorthogonal labeling of membrane proteins, improved understanding of membrane dynamics and fluidity, and the generation of new probes for biosensing assays. [ABSTRACT FROM AUTHOR]

We introduce a method, single-particle profiler, that provides single-particle information on the content and biophysical properties of thousands of particles in the size range 5–200 nm. We use our single-particle profiler to measure the messenger RNA encapsulation efficiency of lipid nanoparticles, the viral binding efficiencies of different nanobodies, and the biophysical heterogeneity of liposomes, lipoproteins, exosomes and viruses. Lipid nanoparticles, viruses, exosomes and liposomes are characterized by analysis of fluorescence fluctuations. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs), including exosomes and microvesicles, mediate intercellular communication in cancer, from development to metastasis. EV‐based liquid biopsy is a promising strategy for cancer diagnosis as EVs can be found in cancer patients' body fluids. In this study, the lipid composition of breast cancer‐derived EVs was studied as well as the potential of blood plasma EVs for the identification of lipid biomarkers for breast cancer detection. Initially, an untargeted lipidomic analysis was carried out for a panel of cancerous and non‐cancerous mammary epithelial cells and their secreted EVs. We found that breast cancer‐derived EVs are enriched in sphingolipids and glycerophospholipids compared to their parental cells. The initial in vitro study showed that EVs and their parental cells can be correctly classified (100% accuracy) between cancerous and non‐cancerous, as well as into their respective breast cancer subtypes, based on their lipid composition. Subsequently, an untargeted lipidomic analysis was carried out for blood plasma EVs from women diagnosed with breast cancer (primary or progressive metastatic breast cancer) as well as healthy women. Correspondingly, when blood plasma EVs were analysed, breast cancer patients and healthy women were correctly classified with an overall accuracy of 93.1%, based on the EVs' lipid composition. Similarly, the analysis of patients with primary breast cancer and healthy women showed an overall accuracy of 95% for their correct classification. Furthermore, primary and metastatic breast cancers were correctly classified with an overall accuracy of 89.5%. This reveals that the blood plasma EVs' lipids may be a promising source of biomarkers for detection of breast cancer. Additionally, this study demonstrates the usefulness of untargeted lipidomics in the study of EV lipid composition and EV‐associated biomarker discovery studies. This is a proof‐of‐concept study and a starting point for further analysis on the identification of EV‐based biomarkers for breast cancer. [ABSTRACT FROM AUTHOR]

The article discusses the use of alumina tubes for longitudinal intracellular monitoring in live cells. It mentions the use of cell cultures for cell heterogeneity, and states that alumina tubes have messenger RNA that reduce cell viability. It also mentions the identification of cell membrane through enzymatic assays or polymerase chain reaction (PCR).

Diagnostic and therapeutic nanoparticles have been actively investigated for the last few decades as new platforms for biomedical applications. Despite their great versatility and potency, nanoparticles have generally required further modification with biocompatible materials such as biopolymers and synthetic polymers for in vivo administration to improve their biological functions, stability, and biocompatibility. Among a variety of natural and synthetic biomaterials, hyaluronate (HA) has been considered a promising biomolecule with which to construct nanohybrid systems, as it can enable long-term and efficient delivery of nanoparticles to target sites as well as physiological stabilization of nanoparticles by forming hydrophilic shells. In this review, we first describe various kinds of HA derivatives and their interactions with nanoparticles, and discuss how to design and develop optimal HA-nanoparticle hybrid systems for biomedical applications. Furthermore, we show several exemplary applications of HA-nanoparticle hybrid systems and provide our perspectives to their futuristic translational applications. Unlabelled Image • Hyaluronate (HA) is used to construct multifunctional nanohybrid systems. • HA enables the long-term and facilitated delivery of nanoparticles to target sites. • HA-nanoparticle systems can be used for diagnostic, therapeutic and theranostic applications. • HA-based nanohybrid systems seem promising for further clinical applications. [ABSTRACT FROM AUTHOR]

Cubosomen sind hochstabile Nanopartikel, die aus einer kubischen Lipidphase gebildet und durch eine polymerbasierte äußere Hülle stabilisiert werden. Lipidische kubische Phasen bestehen aus einer einzigen Lipid‐Doppelschicht, die eine kontinuierliche periodische Membran‐Gitterstruktur mit Poren aufweist, die von zwei miteinander verwobenen Wasserkanälen gebildet wird. Die Porengröße kann durch die Cubosom‐Zusammensetzung angepasst werden. Dabei können die Cubosomen auch bioaktive Lipide enthalten. Zusätzlich kann die äußere Polymerhülle als Target verwendet werden und ist unter physiologischen Bedingungen sehr stabil. Die Cubosomstruktur bietet eine deutlich höhere Membranoberfläche für die Beladung von Membranproteinen und kleinen Wirkstoffmolekülen als Liposomen. Aufgrund der jüngsten Fortschritte können sie in vitro sowohl als Bulkmaterial als auch als Nanopartikel für Wirkstoff‐Transporte, Membranbioreaktoren, künstliche Zellen und Biosensoren genutzt werden. Dieser Aufsatz skizziert die jüngsten Fortschritte in der Cubosom‐Technologie und liefert Empfehlungen für die zielgerichtete Entwicklung neuer Systeme für biomedizinische Anwendungen. Cubosomen sind Nanopartikel mit einer inneren periodischen Lipidmembran, die durch zwei spezifische Wasserkanäle separiert ist. Die Oberfläche wird durch eine polymere Außenhülle stabilisiert. Die Schlüsselfaktoren für die gezielte Entwicklung von Cubosomen für maßgeschneiderte Anwendungen, einschließlich Wirkstofftransport, Biosensorik und medizinische Anwendungen, werden in diesem Aufsatz beschrieben. [ABSTRACT FROM AUTHOR]

Cubosomes are highly stable nanoparticles formed from the lipid cubic phase and stabilized by a polymer based outer corona. Bicontinuous lipid cubic phases consist of a single lipid bilayer that forms a continuous periodic membrane lattice structure with pores formed by two interwoven water channels. Cubosome composition can be tuned to engineer pore sizes or include bioactive lipids, the polymer outer corona can be used for targeting and they are highly stable under physiological conditions. Compared to liposomes, the structure provides a significantly higher membrane surface area for loading of membrane proteins and small drug molecules. Owing to recent advances, they can be engineered in vitro in both bulk and nanoparticle formats with applications including drug delivery, membrane bioreactors, artificial cells, and biosensors. This review outlines recent advances in cubosome technology enabling their application and provides guidelines for the rational design of new systems for biomedical applications. Cubosomes are nanoparticles with an internal periodic lipid membrane separated by two distinct water channels. The surface is stabilized by a polymer outer corona. Recent advances have enabled the rational design of cubosome systems. Key considerations are outlined for engineering cubosomes for tailor‐made applications including delivery, biosensing, and medical applications. [ABSTRACT FROM AUTHOR]

The article discusses research being done on a new 3D model of liver tissue to assess the toxicity of various nanoparticles. It references a study by Nicholas Kotov and colleagues of the University of Michigan. According to the study, the new cultur model aims to bridge the gap between in vitro and in vivo testing of nanoparticles.

All vertebrates possess mechanisms to restore damaged tissues with outcomes ranging from regeneration to scarring. Unfortunately, the mammalian response to tissue injury most often culminates in scar formation. Accounting for nearly 45% of deaths in the developed world, fibrosis is a process that stands diametrically opposed to functional tissue regeneration. Strategies to improve wound healing outcomes therefore require methods to limit fibrosis. Wound healing is guided by precise spatiotemporal deposition and remodelling of the extracellular matrix (ECM). The ECM, comprising the non-cellular component of tissues, is a signalling depot that is differentially regulated in scarring and regenerative healing. This Review focuses on the importance of the native matrix components during mammalian wound healing alongside a comparison to scar-free healing and then presents an overview of matrix-based strategies that attempt to exploit the role of the ECM to improve wound healing outcomes. [ABSTRACT FROM AUTHOR]

Tissue engineering (TE) has the potential to improve the outcome for patients with osteoarthritis (OA). The successful clinical translation of this technique as part of a therapy requires the ability to measure extracellular matrix (ECM) production of engineered tissues in vitro , in order to ensure quality control and improve the likelihood of tissue survival upon implantation. Conventional techniques for assessing the ECM content of engineered cartilage, such as biochemical assays and histological staining are inherently destructive. Raman spectroscopy, on the other hand, represents a non-invasive technique for in situ biochemical characterization. Here, we outline current roadblocks in translational Raman spectroscopy in TE and introduce a comprehensive workflow designed to non-destructively monitor and quantify ECM biomolecules in large (>3 mm), live cell TE constructs online. Diffuse near-infrared fiber-optic Raman spectra were measured from live cell cartilaginous TE constructs over a 56-day culturing period. We developed a multivariate curve resolution model that enabled quantitative biochemical analysis of the TE constructs. Raman spectroscopy was able to non-invasively quantify the ECM components and showed an excellent correlation with biochemical assays for measurement of collagen (R 2 = 0.84) and glycosaminoglycans (GAGs) (R 2 = 0.86). We further demonstrated the robustness of this technique for online prospective analysis of live cell TE constructs. The fiber-optic Raman spectroscopy strategy developed in this work offers the ability to non-destructively monitor construct growth online and can be adapted to a broad range of TE applications in regenerative medicine toward controlled clinical translation. [ABSTRACT FROM AUTHOR]

Background: Stochastic optical reconstruction microscopy (STORM), a super-resolution microscopy technique based on single-molecule localizations, has become popular to characterize sub-diffraction limit targets. However, due to lengthy image acquisition, STORM recordings are prone to sample drift. Existing cross-correlation or fiducial marker-based algorithms allow correcting the drift within each channel, but misalignment between channels remains due to interchannel drift accumulating during sequential channel acquisition. This is a major drawback in multi-color STORM, a technique of utmost importance for the characterization of various biological interactions. Results: We developed RegiSTORM, a software for reducing channel misalignment by accurately registering STORM channels utilizing fiducial markers in the sample. RegiSTORM identifies fiducials from the STORM localization data based on their non-blinking nature and uses them as landmarks for channel registration. We first demonstrated accurate registration on recordings of fiducials only, as evidenced by significantly reduced target registration error with all the tested channel combinations. Next, we validated the performance in a more practically relevant setup on cells multi-stained for tubulin. Finally, we showed that RegiSTORM successfully registers two-color STORM recordings of cargo-loaded lipid nanoparticles without fiducials, demonstrating the broader applicability of this software. Conclusions: The developed RegiSTORM software was demonstrated to be able to accurately register multiple STORM channels and is freely available as open-source (MIT license) at and (archived), and runs as a standalone executable (Windows) or via Python (Mac OS, Linux). [ABSTRACT FROM AUTHOR]

Bioglass was the first synthetic biomaterial that formed a chemical bond to bone. Although bioactive glass scaffolds can mimic bone's porous structure, they are brittle. Sol-gel derived hybrids could overcome this problem because their nanoscale conetworks of silica and organic polymer have the potential to provide unique physical properties and controlled homogeneous biodegradation. Copolymers of methyl methacrylate (MMA) and 3-(trimethoxysilyl)propyl methacrylate (TMSPMA) have been used as an organic source for hybrids to take advantage of their self-hardening property. However, the effect of well-defined poly(MMA-co-TMSPMA) architecture in the hybrid system has not been investigated. Here, linear, randomly branched, and star shaped methacrylate based copolymers were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization method. These copolymers were then used to fabricate hybrids. The 3-D polymer structure had a significant effect on mechanical properties, providing higher strain to failure while maintaining a compressive strength similar to sol-gel glass. Star copolymer-SiO2 hybrids had a modulus of toughness 9.6-fold greater and Young's modulus 4.5-fold lower than a sol-gel derived bioactive glass. During in vitro cell culture, MC3T3-E1 osteoblast precursor cells adhered on the surface regardless of the polymer structure. Introducing star polymers to inorganic-organic hybrids opens up possibilities for the fine-tuning physical properties of bone scaffold materials. [ABSTRACT FROM AUTHOR]

Hybrid self-assembly has become a reliable approach to synthesize soft materials with multiple levels of structural complexity and synergistic functionality. In this work, photoluminescent graphene quantum dots (GQDs, 2-5 nm) are used for the first time as molecule-like building blocks to construct self-assembled hybrid materials for label-free biosensors. Ionic self-assembly of disc-shaped GQDs and charged biopolymers is found to generate a series of hierarchical structures that exhibit aggregation-induced fluorescence quenching of the GQDs and change the protein/polypeptide secondary structure. The integration of GQDs and biopolymers via self-assembly offers a flexible toolkit for the design of label-free biosensors in which the GQDs serve as a fluorescent probe and the biopolymers provide biological function. The versatility of this approach is demonstrated in the detection of glycosaminoglycans (GAGs), pH, and proteases using three strategies: 1) competitive binding of GAGs to biopolymers, 2) pH-responsive structural changes of polypeptides, and 3) enzymatic hydrolysis of the protein backbone, respectively. It is anticipated that the integrative self-assembly of biomolecules and GQDs will open up new avenues for the design of multifunctional biomaterials with combined optoelectronic properties and biological applications. [ABSTRACT FROM AUTHOR]

We report on the use of high resolution Raman spectroscopy mapping combined with a micro-engineered stem cell platform. This technique obtains quantitative information about the concentration of individual intracellular molecules such as proteins, lipids, and other metabolites, while tightly controlling cell shape and adhesion. This new quantitative analysis will prove highly relevant for in vitro drug screening applications and regenerative medicine. [ABSTRACT FROM AUTHOR]

The article presents a study which showed that the activation of non-muscle myosin IIC (NM IIC) or physical restriction to young topology improves in vitro regeneration by old epithelium. Topics discussed include contribution of various cell types to the overall curvature of the intestinal niche in the domains at the bottom of the crypts of self-organized organoids, effect of high surface-to-volume ratio on signal reception in intestinal stem cells (ISCs,) and preparation of collagen scaffold.

Constructing artificial systems that effectively replace or supplement natural biological machinery within cells is one of the fundamental challenges underpinning bioengineering. At the sub‐cellular scale, artificial organelles (AOs) have significant potential as long‐acting biomedical implants, mimicking native organelles by conducting intracellularly compartmentalized enzymatic actions. The potency of these AOs can be heightened when judiciously combined with genetic engineering, producing highly tailorable biohybrid cellular systems. Here, the authors present a cost‐effective, microliter scale (10 µL) polymersome (PSome) synthesis based on polymerization‐induced self‐assembly for the in situ encapsulation of Gaussia luciferase (GLuc), as a model luminescent enzyme. These GLuc‐loaded PSomes present ideal features of AOs including enhanced enzymatic resistance to thermal, proteolytic, and intracellular stresses. To demonstrate their biomodulation potential, the intracellular luminescence of GLuc‐loaded PSomes is coupled to optogenetically engineered cardiomyocytes, allowing modulation of cardiac beating frequency through treatment with coelenterazine (CTZ) as the substrate for GLuc. The long‐term intracellular stability of the luminescent AOs allows this cardiostimulatory phenomenon to be reinitiated with fresh CTZ even after 7 days in culture. This synergistic combination of organelle‐mimicking synthetic materials with genetic engineering is therefore envisioned as a highly universal strategy for the generation of new biohybrid cellular systems displaying unique triggerable properties. [ABSTRACT FROM AUTHOR]

A general strategy for the preparation of aligned multi-walled carbon nanotube (AMWCNT)/inorganic composites and aligned nanostructures was realized by synthesizing materials within an AMWCNT/hydrogel composite template. Chemical reactions that could damage the AMWCNT structure are not necessary in this strategy. AMWCNT composites of many materials were synthesized. Three typical and popularly used materials were present to show the versatility of the strategy: hydroxyapatite, alumina, and silver. The morphologies of the materials formed on the nanotube surface include continuous layers, nanoparticles, and microspheres. The structures formed after the removal of AMWCNTs include aligned nanofibers, aligned nanotubes, and particles. [ABSTRACT FROM AUTHOR]

Efficient signal amplification processesare key to the designof sensitive assays for biomolecule detection. Here, we describe anew assay platform that takes advantage of both polymerization reactionsand the aggregation of nanoparticles to amplify signal. In our design,a cascade is set up in which radicals generated by either enzymesor metal ions are polymerized to form polymers that can entangle multiplegold nanoparticles (AuNPs) into aggregates, resulting in a visiblecolor change. Less than 0.05% monomer-to-polymer conversion is requiredto initiate aggregation, providing high sensitivity toward the radicalgenerating species. Good sensitivity of this assay toward horseradishperoxidase, catalase, and parts per billion concentrations of ironand copper is shown. Incorporation of the oxygen-consuming enzymeglucose oxidase (GOx), enables this assay to be performed in openair conditions at ambient temperature. We anticipate that such a designwill provide a useful platform for sensitive detection of a broadrange of biomolecules through polymerization-based amplification. [ABSTRACT FROM AUTHOR]

The development of novel assays for protease sensing plays an important role in clinical diagnostics and therapeutics. Herein, we report a supramolecular platform for label-free protease detection, based on protein/dye self-assembly and enzyme-triggered disassembly. In a typical case, coassembly of protamine sulfate and perylene dye via electrostatic attractions and π-π interactions caused significant colorimetric and fluorescent responses. Subsequent addition of trypsin was found to cleave the amide bonds of protein, triggering the dissociation of protein/dye aggregates and the release of perylene dyes. The enzyme-triggered disassembly was transduced into multiple readouts including absorption, fluorescence, and polarization, which were exploited for trypsin detection and inhibitor testing. This assay was also used for tum-on fluorescence detection of cathepsin B, an enzyme known to be overexpressed in mammalian cancer cells. The integration of supramolecular self-assembly into enzyme detection in this work has provided a novel label-free biosensing platform which is highly sensitive with multimodal readouts. The relative simplicity of the approach avoids the need for time-consuming substrate synthesis, and is also amenable to naked eye detection. [ABSTRACT FROM AUTHOR]

The application of nanomaterials to detect disease biomarkers is giving rise to ultrasensitive assays, with scientists exploiting the many advantageous physical and chemical properties of nanomaterials. The fundamental basis of such work is to link unique phenomena that arise at the nanoscale to the presence of a specific analyte biomolecule, and to modulate the intensity of such phenomena in a ratiometric fashion, in direct proportion with analyte concentration. Precise engineering of nanomaterial surfaces is of utmost importance here, as the interface between the material and the biological environment is where the key interactions occur. In this tutorial review, we discuss the use of plasmonic nanomaterials in the development of biodiagnostic tools for the detection of a large variety of biomolecular analytes, and how their plasmonic properties give rise to tunable optical characteristics and surface enhanced Raman signals. We put particular focus on studies that have explored the efficacy of the systems using physiological samples in an effort to highlight the clinical potential of such assays. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) play a key role in many physiological and pathophysiological processes and hold great potential for therapeutic and diagnostic use. Despite significant advances within the last decade, the key issue of EV storage stability remains unresolved and under investigated. Here, we aimed to identify storage conditions stabilizing EVs and comprehensively compared the impact of various storage buffer formulations at different temperatures on EVs derived from different cellular sources for up to 2 years. EV features including concentration, diameter, surface protein profile and nucleic acid contents were assessed by complementary methods, and engineered EVs containing fluorophores or functionalized surface proteins were utilized to compare cellular uptake and ligand binding. We show that storing EVs in PBS over time leads to drastically reduced recovery particularly for pure EV samples at all temperatures tested, starting already within days. We further report that using PBS as diluent was found to result in severely reduced EV recovery rates already within minutes. Several of the tested new buffer conditions largely prevented the observed effects, the lead candidate being PBS supplemented with human albumin and trehalose (PBS‐HAT). We report that PBS‐HAT buffer facilitates clearly improved short‐term and long‐term EV preservation for samples stored at ‐80°C, stability throughout several freeze‐thaw cycles, and drastically improved EV recovery when using a diluent for EV samples for downstream applications. [ABSTRACT FROM AUTHOR]

Abstract: Enzymes are key components of the bionanotechnology toolbox that possess exceptional biorecognition capabilities and outstanding catalytic properties. When combined with the unique physical properties of nanomaterials, the resulting enzyme-responsive nanoparticles can be designed to perform functions efficiently and with high specificity for the triggering stimulus. This powerful concept has been successfully applied to the fabrication of drug delivery schemes where the tissue of interest is targeted via release of cargo triggered by the biocatalytic action of an enzyme. Moreover, the chemical transformation of the carrier by the enzyme can also generate therapeutic molecules, therefore paving the way to design multimodal nanomedicines with synergistic effects. Dysregulation of enzymatic activity has been observed in a number of severe pathological conditions, and this observation is useful not only to program drug delivery in vivo but also to fabricate ultrasensitive sensors for diagnosing these diseases. In this review, several enzyme-responsive nanomaterials such as polymer-based nanoparticles, liposomes, gold nanoparticles and quantum dots are introduced, and the modulation of their physicochemical properties by enzymatic activity emphasized. When known, toxicological issues related to the utilization nanomaterials are highlighted. Key examples of enzyme-responsive nanomaterials for drug delivery and diagnostics are presented, classified by the type of effector biomolecule, including hydrolases such as proteases, lipases and glycosidases, and oxidoreductases. [Copyright &y& Elsevier]