Apoptotic extracellular vesicles derived from hypoxia-preconditioned mesenchymal stem cells within a modified gelatine hydrogel promote osteochondral regeneration by enhancing stem cell activity and regulating immunity.

Due to its unique structure, articular cartilage has limited abilities to undergo self-repair after injury. Additionally, the repair of articular cartilage after injury has always been a difficult problem in the field of sports medicine. Previous studies have shown that the therapeutic use of mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) has great potential for promoting cartilage repair. Recent studies have demonstrated that most transplanted stem cells undergo apoptosis in vivo, and the apoptotic EVs (ApoEVs) that are subsequently generated play crucial roles in tissue repair. Additionally, MSCs are known to exist under low-oxygen conditions in the physiological environment, and these hypoxic conditions can alter the functional and secretory properties of MSCs as well as their secretomes. This study aimed to investigate whether ApoEVs that are isolated from adipose-derived MSCs cultured under hypoxic conditions (hypoxic apoptotic EVs [H-ApoEVs]) exert greater effects on cartilage repair than those that are isolated from cells cultured under normoxic conditions. Through in vitro cell proliferation and migration experiments, we demonstrated that H-ApoEVs exerted enhanced effects on stem cell proliferation, stem cell migration, and bone marrow derived macrophages (BMDMs) M2 polarization compared to ApoEVs. Furthermore, we utilized a modified gelatine matrix/3D-printed extracellular matrix (ECM) scaffold complex as a carrier to deliver H-ApoEVs into the joint cavity, thus establishing a cartilage regeneration system. The 3D-printed ECM scaffold provided mechanical support and created a microenvironment that was conducive to cartilage regeneration, and the H-ApoEVs further enhanced the regenerative capacity of endogenous stem cells and the immunomodulatory microenvironment of the joint cavity; thus, this approach significantly promoted cartilage repair. In conclusion, this study confirmed that a ApoEVs delivery system based on a modified gelatine matrix/3D-printed ECM scaffold together with hypoxic preconditioning enhances the functionality of stem cell-derived ApoEVs and represents a promising approach for promoting cartilage regeneration.

Geometric lightguide for near-eye light field displays.

Most near-eye displays with one fixed focal plane suffer from the vergence-accommodation conflict and cause visual discomfort to users. In contrast, light field displays can provide natural and comfortable 3D visual sensation to users without the conflict. This paper presents a near-eye light field display consisting of a geometric lightguide and a light field generator, along with a collimator to ensure the light rays propagating in the lightguide are collimated. Unlike most lightguides, which reduce thickness by employing total internal reflection that can easily generate stray light, our lightguide directly propagates light rays without total internal reflection. The partially reflective mirrors of the lightguide expand the exit pupil to achieve an eyebox of 13m m(h o r i z o n t a l)×6.5m m(v e r t i c a l) with an eye relief of 18 mm. The collimator and the light field generator, both having effective focal lengths different in the horizontal and vertical directions, are designed to provide a 40-deg diagonal field of view. The working range of the light field generator, which is 30 cm to infinity, is verified qualitatively and quantitatively by experiments. We optimize the illuminance uniformity and analyze the illuminance variation across the eyebox. Further, we minimize the ghost artifact (referring to the split-up of light fields replicated by the partially reflective mirrors) by orienting the partially reflective mirrors at slightly different angles to enhance the image quality for short-range applications such as medical surgery.

Effect of Protein-Glutaminase on Calcium Sulphate-Induced Gels of SPI with Different Thermal Treatments.

The effects of protein-glutaminase (PG) on calcium sulphate (CaSO4)-induced gels of soy protein isolate (SPI) with different heat treatment levels were investigated. The time-dependent degree of deamidation showed that the mild denaturation of the protein favored the deamidation. The particle size distribution showed that the heat treatment increased the SPI particle size, and the particle size distribution of the SPI shifted to the right or increased the proportion of the large particle size component as the degree of deamidation increased for each sample. Rheological analysis showed that the deamidation substantially pushed up the gel temperature and decreased the value of G'. The gel strength and water-holding capacity showed that the higher the amount of enzyme added, the more significant the decrease in gel strength, while the gel water-holding capacity increased. In summary, the deamidation of PG and heat treatment can affect the gel properties of SPI synergistically.

Effect of Ionic Strength on Heat-Induced Gelation Behavior of Soy Protein Isolates with Ultrasound Treatment.

This study investigated the effect of ultrasound on gel properties of soy protein isolates (SPIs) at different salt concentrations. The results showed that ultrasound could significantly improve the gel hardness and the water holding capacity (WHC) of the salt-containing gel (p < 0.05). The gel presents a uniform and compact three-dimensional network structure. The combination of 200 mM NaCl with 20 min of ultrasound could significantly increase the gel hardness (four times) and the WHC (p < 0.05) compared with the SPI gel without treatment. With the increase in NaCl concentration, the ζ potential and surface hydrophobicity increased, and the solubility decreased. Ultrasound could improve the protein solubility, compensate for the loss of solubility caused by the addition of NaCl, and further increase the surface hydrophobicity. Ultrasound combined with NaCl allowed proteins to form aggregates of different sizes. In addition, the combined treatment increased the hydrophobic interactions and disulfide bond interactions in the gel. Overall, ultrasound could improve the thermal gel properties of SPI gels with salt addition.

Effects of soy protein composition in recombined soy-based cream on the stability and physical properties of whipping cream.

BACKGROUND: Recombinant plant-based whipping cream (RSWC) has been widely studied in recent years. The present study investigated the effects of soybean protein and its hydrolysates on the stability and physical properties of the RSWC. The RSWC was made with 28% soybean oil bodies and 4% additional soy proteins or its hydrolysates. The proteins used were soy protein isolate, 7S, 11S, oil body protein, soybean proteins isolate hydrolyzed by pepsin (SPHPe) and soybean protein isolate hydrolyzed by papain (SPHPa). RESULTS: RSWC made with SPHPa containing a large amount of small-molecule polypeptide had the lowest apparent viscosity, shortest whipping time, best overrun and worst whipping stability, whereas RSWC made with SPHPe containing the α, ß subunit and small-molecule polypeptides exhibited the second highest overrun and best whipping stability. The partial coalescence of fat and confocal micrographs of cream emulsions suggested that oil body protein was displaced by the small peptides from the interface, which led to partial destabilization and sufficient coalescence of fat globules after aging and whipping. CONCLUSION: Selectively hydrolyzed soy protein, such as SPHPe, can be used for the production of RSWC with sufficient overrun and whipping stability. This research is of great significance and opens a route to production of the recombinant plant-based cream in the future. © 2020 Society of Chemical Industry.

Cascaded DBR plasmonic cavity lens for far-field subwavelength imaging at a visible wavelength.

We experimentally demonstrate a novel cascaded plasmonic superlens, which can directly image subwavelength objects with magnification in the far field at a wavelength of 640nm. The lens consists of two plasmonic slabs. One is a plasmonic cavity lens used for near-field coupling, and the other one is a planar plasmonic lens for phase compensation and thus, image magnification. To tune the performance wavelength to visible and to enhance the near-field transmission, distributed Bragg reflectors are integrated to the plasmonic cavity lens around the lens center, forming additional lateral cavities for surface waves. In this article, we first show numerical results about the working principle and the performance of the lens. Then, we demonstrate the imaging performance of a fabricated superlens experimentally. The fabricated superlens exhibits a lateral resolution down to 200 nm at the wavelength of 640 nm observed in the far field. Compared to our earlier design, shift invariance is achieved with the current approach. Our results could open a way for designing and fabricating novel miniaturized plasmonic superlenses in the future.

Cascaded plasmonic superlens for far-field imaging with magnification at visible wavelength.

We experimentally demonstrate a novel design of a cascaded plasmonic superlens, which can directly image subwavelength objects with magnification in the far field at visible wavelengths. The lens consists of two cascaded plasmonic slabs. One is a plasmonic metasurface used for near field coupling, and the other one is a planar plasmonic lens used for phase compensation and thus image magnification. First, we show numerical calculations about the performance of the lens. Based on these results we then describe the fabrication of both sub-structures and their combination. Finally, we demonstrate imaging performance of the lens for a subwavelength double-slit object as an example. The fabricated superlens exhibits a lateral resolution down to 180 nm at a wavelength of 640 nm, as predicted by numerical calculations. This might be the first experimental demonstration in which a planar plasmonic lens is employed for near-field image magnification. Our results could open a way for designing and fabricating novel miniaturized plasmonic superlenses in the future.

Depolarization of a randomly distributed plasmonic meander metasurface characterized by Mueller matrix spectroscopic ellipsometry.

Metallic nanostructures offer efficient solutions in polarization control with a very low thickness. In this report, we investigate the optical properties of a nano-fabricated plasmonic pseudo-depolarizer using Mueller matrix spectroscopic ellipsometry in transmission configuration. The depolarizer is composed of 256 square cells, each containing a periodically corrugated metallic film with random orientation. The full Mueller matrix was analyzed as a function of incident angle in a range between 0 and 20° and over the whole rotation angle range. Depolarization could be achieved in two visible wavelength regions around the short-range and long-range surface plasmon polariton frequencies, respectively. Furthermore, depolarization for circularly polarized light was 2.5 times stronger than that for linearly polarized light. Our results could work as a guidance for realizing a broadband high efficiency dielectric metasurface depolarizers.

Rigorous speckle simulation using surface integral equations and higher order boundary element method.

The scattering of electromagnetic waves from rough surfaces has been actively studied for more than a century now because of its involvement in vast application areas. In the past two decades, great advances have been made by incorporating multiple scattering effects into analytical approaches. However, no model can yet be applied to surfaces with arbitrary roughness. It is also very difficult to study the cross-polarization, shadowing, or multiple scattering effects. In order to study more fundamentally the interaction of polarized light with more general rough surfaces of general media, we have developed a rigorous numerical simulator to calculate the resulting speckle fields. The full Maxwell equations were solved using surface integral equations combined with a boundary element method. The rough surface was discretized by higher order quadrilateral edge elements. The effective tangential electric and magnetic fields in each element in terms of 10 edges were first solved. The scattered electric and magnetic fields everywhere in space were then calculated correspondingly. One of the great advantages of such a simulator is that both the near and far fields can be calculated directly. Preliminary results of different kinds of metallic structures are presented, by which the advantages of the method are demonstrated.

Constant force grinding controller for robots based on SAC optimal parameter finding algorithm.

Since conventional PID (Proportional-Integral-Derivative) controllers hardly control the robot to stabilize for constant force grinding under changing environmental conditions, it is necessary to add a compensation term to conventional PID controllers. An optimal parameter finding algorithm based on SAC (Soft-Actor-Critic) is proposed to solve the problem that the compensation term parameters are difficult to obtain, including training state action and normalization preprocessing, reward function design, and targeted deep neural network design. The algorithm is used to find the optimal controller compensation term parameters and applied to the PID controller to complete the compensation through the inverse kinematics of the robot to achieve constant force grinding control. To verify the algorithm's feasibility, a simulation model of a grinding robot with sensible force information is established, and the simulation results show that the controller trained with the algorithm can achieve constant force grinding of the robot. Finally, the robot constant force grinding experimental system platform is built for testing, which verifies the control effect of the optimal parameter finding algorithm on the robot constant force grinding and has specific environmental adaptability.

Training With Uncertain Annotations for Semantic Segmentation of Basal Cell Carcinoma From Full-Field OCT Images.

Semantic segmentation of basal cell carcinoma (BCC) from full-field optical coherence tomography (FF-OCT) images of human skin has received considerable attention in medical imaging. However, it is challenging for dermatopathologists to annotate the training data due to OCT's lack of color specificity. Very often, they are uncertain about the correctness of the annotations they made. In practice, annotations fraught with uncertainty profoundly impact the effectiveness of model training and hence the performance of BCC segmentation. To address this issue, we propose an approach to model training with uncertain annotations. The proposed approach includes a data selection strategy to mitigate the uncertainty of training data, a class expansion to consider sebaceous gland and hair follicle as additional classes to enhance the performance of BCC segmentation, and a self-supervised pre-training procedure to improve the initial weights of the segmentation model parameters. Furthermore, we develop three post-processing techniques to reduce the impact of speckle noise and image discontinuities on BCC segmentation. The mean Dice score of BCC of our model reaches 0.503±0.003, which, to the best of our knowledge, is the best performance to date for semantic segmentation of BCC from FF-OCT images.

Effect of tetrahedral framework nucleic acids on the reconstruction of tendon-to-bone injuries after rotator cuff tears.

Clinicians and researchers have always faced challenges in performing surgery for rotator cuff tears (RCT) due to the intricate nature of the tendon-bone gradient and the limited long-term effectiveness. At the same time, the occurrence of an inflammatory microenvironment further aggravates tissue damage, which has a negative impact on the regeneration process of mesenchymal stem cells (MSCs) and eventually leads to the production of scar tissue. Tetrahedral framework nucleic acids (tFNAs), novel nanomaterials, have shown great potential in biomedicine due to their strong biocompatibility, excellent cellular internalisation ability, and unparalleled programmability. The objective of this research was to examine if tFNAs have a positive effect on regeneration after RCTs. Experiments conducted in a controlled environment demonstrated that tFNAs hindered the assembly of inflammasomes in macrophages, resulting in a decrease in the release of inflammatory factors. Next, tFNAs were shown to exert a protective effect on the osteogenic and chondrogenic differentiation of bone marrow MSCs under inflammatory conditions. The in vitro results also demonstrated the regulatory effect of tFNAs on tendon-related protein expression levels in tenocytes after inflammatory stimulation. Finally, intra-articular injection of tFNAs into a rat RCT model showed that tFNAs improved tendon-to-bone healing, suggesting that tFNAs may be promising tendon-to-bone protective agents for the treatment of RCTs.

Toward cell nuclei precision between OCT and H&E images translation using signal-to-noise ratio cycle-consistency.

Medical image-to-image translation is often difficult and of limited effectiveness due to the differences in image acquisition mechanisms and the diverse structure of biological tissues. This work presents an unpaired image translation model between in-vivo optical coherence tomography (OCT) and ex-vivo Hematoxylin and eosin (H&E) stained images without the need for image stacking, registration, post-processing, and annotation. The model can generate high-quality and highly accurate virtual medical images, and is robust and bidirectional. Our framework introduces random noise to (1) blur redundant features, (2) defend against self-adversarial attacks, (3) stabilize inverse conversion, and (4) mitigate the impact of OCT speckles. We also demonstrate that our model can be pre-trained and then fine-tuned using images from different OCT systems in just a few epochs. Qualitative and quantitative comparisons with traditional image-to-image translation models show the robustness of our proposed signal-to-noise ratio (SNR) cycle-consistency method.

Incorporation of Magnesium Ions into an Aptamer-Functionalized ECM Bioactive Scaffold for Articular Cartilage Regeneration.

The regeneration and reconstruction of articular cartilage (AC) after a defect are often difficult. The key to the treatment of AC defects lies in regeneration of the defect site and regulation of the inflammatory response. In this investigation, a bioactive multifunctional scaffold was formulated using the aptamer Apt19S as a mediator for mesenchymal stem cell (MSC)-specific recruitment and the enhancement of cellular chondrogenic and inflammatory regulation through the incorporation of Mg2+. Apt19S, which can recruit MSCs in vitro and in vivo, was chemically conjugated to a decellularized cartilage extracellular matrix (ECM)-lysed scaffold. The results from in vitro experiments using the resulting scaffold demonstrated that the inclusion of Mg2+ could stimulate not only the chondrogenic differentiation of synovial MSCs but also the increased polarization of macrophages toward the M2 phenotype. Additionally, Mg2+ inhibited NLRP3 inflammasome activation, thereby decreasing chondrocyte pyroptosis. Subsequently, Mg2+ was incorporated into the bioactive multifunctional scaffold, and the resulting scaffold promoted cartilage regeneration in vivo. In conclusion, this study confirms that the combination of Mg2+ and aptamer-functionalized ECM scaffolds is a promising strategy for AC regeneration based on in situ tissue engineering and early inflammatory regulation.

Recent advances in tendon tissue engineering strategy.

Tendon injuries often result in significant pain and disability and impose severe clinical and financial burdens on our society. Despite considerable achievements in the field of regenerative medicine in the past several decades, effective treatments remain a challenge due to the limited natural healing capacity of tendons caused by poor cell density and vascularization. The development of tissue engineering has provided more promising results in regenerating tendon-like tissues with compositional, structural and functional characteristics comparable to those of native tendon tissues. Tissue engineering is the discipline of regenerative medicine that aims to restore the physiological functions of tissues by using a combination of cells and materials, as well as suitable biochemical and physicochemical factors. In this review, following a discussion of tendon structure, injury and healing, we aim to elucidate the current strategies (biomaterials, scaffold fabrication techniques, cells, biological adjuncts, mechanical loading and bioreactors, and the role of macrophage polarization in tendon regeneration), challenges and future directions in the field of tendon tissue engineering.

Hierarchical porous ECM scaffolds incorporating GDF-5 fabricated by cryogenic 3D printing to promote articular cartilage regeneration.

BACKGROUND: In recent years, there has been significant research progress on in situ articular cartilage (AC) tissue engineering with endogenous stem cells, which uses biological materials or bioactive factors to improve the regeneration microenvironment and recruit more endogenous stem cells from the joint cavity to the defect area to promote cartilage regeneration. METHOD: In this study, we used ECM alone as a bioink in low-temperature deposition manufacturing (LDM) 3D printing and then successfully fabricated a hierarchical porous ECM scaffold incorporating GDF-5. RESULTS: Comparative in vitro experiments showed that the 7% ECM scaffolds had the best biocompatibility. After the addition of GDF-5 protein, the ECM scaffolds significantly improved bone marrow mesenchymal stem cell (BMSC) migration and chondrogenic differentiation. Most importantly, the in vivo results showed that the ECM/GDF-5 scaffold significantly enhanced in situ cartilage repair. CONCLUSION: In conclusion, this study reports the construction of a new scaffold based on the concept of in situ regeneration, and we believe that our findings will provide a new treatment strategy for AC defect repair.

Tetrahedral framework nucleic acids enhance the chondrogenic potential of human umbilical cord mesenchymal stem cells via the PI3K/AKT axis.

The field of regenerative medicine faces a notable challenge in terms of the regeneration of articular cartilage. Without proper treatment, it can lead to osteoarthritis. Based on the research findings, human umbilical cord mesenchymal stem cells (hUMSCs) are considered an excellent choice for regenerating cartilage. However, there is still a lack of suitable biomaterials to control their ability to self-renew and differentiate. To address this issue, in this study using tetrahedral framework nucleic acids (tFNAs) as a new method in an in vitro culture setting to manage the behaviour of hUMSCs was proposed. Then, the influence of tFNAs on hUMSC proliferation, migration and chondrogenic differentiation was explored by combining bioinformatics methods. In addition, a variety of molecular biology techniques have been used to investigate deep molecular mechanisms. Relevant results demonstrated that tFNAs can affect the transcriptome and multiple signalling pathways of hUMSCs, among which the PI3K/Akt pathway is significantly activated. Furthermore, tFNAs can regulate the expression levels of multiple proteins (GSK3ß, RhoA and mTOR) downstream of the PI3K-Akt axis to further enhance cell proliferation, migration and hUMSC chondrogenic differentiation. tFNAs provide new insight into enhancing the chondrogenic potential of hUMSCs, which exhibits promising potential for future utilization within the domains of AC regeneration and clinical treatment.

Polarization scramblers with plasmonic meander-type metamaterials.

Due to plasmonic excitations, metallic meander structures exhibit an extraordinarily high transmission within a well-defined pass band. Within this frequency range, they behave like almost ideal linear polarizers, can induce large phase retardation between s- and p-polarized light and show a high polarization conversion efficiency. Due to these properties, meander structures can interact very effectively with polarized light. In this report, we suggest a novel polarization scrambler design using spatially distributed metallic meander structures with random angular orientations. The whole device has an optical response averaged over all pixel orientations within the incident beam diameter. We characterize the depolarizing properties of the suggested polarization scrambler with the Mueller matrix and investigate both single layer and stacked meander structures at different frequencies. The presented polarization scrambler can be flexibly designed to work at any wavelength in the visible range with a bandwidth of up to 100 THz. With our preliminary design, we achieve depolarization rates larger than 50% for arbitrarily polarized monochromatic and narrow-band light. Circularly polarized light could be depolarized by up to 95% at 600 THz.

Lipid nanoparticle-assisted miR29a delivery based on core-shell nanofibers improves tendon healing by cross-regulation of the immune response and matrix remodeling.

Inferior healing and peritendinous adhesions are the major clinical problems following Achilles tendon injury, leading to impaired motor function and an increased risk of re-rupture. These complications are presumed to be inextricably linked to inflammation and fibroscar formation. Here, microRNA29a is identified as a promising therapeutic target for tendon injury through the cross-regulation of the immune response and matrix remodeling. MiR29a-LNPs were successfully prepared by microfluidic technology. They are then loaded into the core-shell nanofibers to achieve local delivery in the injured tendon, where the shell layer is composed of PELA for anti-adhesion. Our studies reveal that miR29a regulates collagen synthesis and NF-κB activation in tenocytes, and promotes macrophage polarization by inhibiting the inflammasome pathway. In vivo studies of the Achilles tendon-rupture model indicate the best repair in the miR29a group, as evidenced by superior collagen composition and alignment, higher mechanical strength, and better functional recovery. In conclusion, a functionalized anti-adhesive membrane that promotes nascent tendon matrix remodeling and improves the regenerative immune microenvironment is developed for the treatment of tendon injury.