Sheng, ShuZhang, SijiaNi, WeidongTian, Huayu...
10页查看更多>>摘要：Because of molecular heterogeneity in tumors, clinical outcomes of tumor treatment are not very satisfactory, and novel strategies are therefore needed to address this challenge. Combination therapy could efficiently enhance tumor treatment by stimulating multiple pathways, reducing the systemic toxicity of monotherapy, and regulating the tumor immune microenvironments. Herein, metal-organic framework MIL-100 (Fe) nanoparticles (NPs) were synthesized by a microwave-assisted method, and oxaliplatin (OXA) and indocyanine green (ICG) were then loaded into hyaluronic acid (HA)-modified MIL-100 NPs to obtain multifunctional nanoparticles (OIMH NPs). The OIMH NPs exhibited sensitive photoacoustic imaging (PAI) for imaging-guided therapy and showed a good synergistic effect by combining chemotherapy with photothermal therapy (PIT) to kill tumor cells. Immunogenic cell death (ICD) and activation of T cells induced by the chemo-photothermal therapy could sensitize for immune checkpoint blockade (aPD-L1) response, thus eliciting systemic antitumor immunity. Finally, tumor inhibition was observed, which could be attributed to the combination of chemotherapy, PIT, and aPD-L1. On the basis of the study findings, an innovative imaging-mediated combined therapeutic strategy involving multifunctional NPs was proposed, which might potentially offer a new clinical treatment for colorectal cancer. Statement of significance The metal-organic framework-mediated chemo-photothermal therapy guided by photoacoustic imaging (PAI) is an accurate and effective approach for tumor inhibition, which can synergistically achieve immunogenic cell death and lead to an increasing infiltration of immune cells in the tumor microenvironment, thereby enhancing the sensitivity for immune checkpoint blockade (aPD-L1) therapy. This type of therapy can not only reduce the systemic toxicity caused by traditional treatment methods, but it can also solve the issue of low response of immune checkpoint blockade in colorectal cancer (CRC). Our study provides experimental evidence for using the combination of immunotherapy and chemo-photothermal therapy against CRC. (C) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
原文链接:
NSTL
Elsevier
Huang, ZhixuanQian, KunChen, JinQi, Yao...
15页查看更多>>摘要：Zeolite-based nanomaterials have a large number of applications in the field of medicine due to their high porosity, biocompatibility and biological stability. In this study, we designed cerium (Ce)-doped Linde Type A (LTA) zeolite-based nanomaterials (Ce/Zeo-NMs) as a multifunctional mesoporous nanoenzyme to reduce dysfunction of the neurovascular unit (NVU) and attenuate cerebral ischaemia-reperfusion (I/R) injury. Owing to its unique adsorption capacity and mimetic catalytic activities, Ce@Zeo-NMs adsorbed excess zinc ions and exhibited scavenging activity against reactive oxygen species (ROS) induced by acute I/R, thus reshaping the oxidative and zinc microenvironment in the ischaemic brain. In vivo results demonstrated that Ce@Zeo-NMs significantly reduced ischaemic damage to the NVU by decreasing the infarct area, protecting against breakdown of the blood-brain barrier (BBB) via inhibiting the degradation of tight junction proteins (TJPs) and inhibiting activation of microglia and astrocytes in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). Taken together, these findings indicated that Ce@Zeo-NMs may serve as a promising dual-targeting therapeutic agent for alleviating cerebral I/R injury. Statement of Significance Cerium (Ce)-doped Linde Type A zeolite-based nanomaterials (Ce/Zeo-NMs) as a multifunctional mesoporous nanoenzyme were designed for inducing neuroprotection after ischaemic stroke by reducing dysfunction of the neurovascular unit (NVU). Ce@Zeo-NMs had the ability to adsorb excessive Zn2+ and showed mimetic enzymatic activities. As a result, Ce@Zeo-NMs protected against cerebral ischaemia and reduced the damage of NVU by improving the integrity of blood brain barrier (BBB) and inhibiting activation of microglia and astrocytes in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). These findings indicated that Ce@Zeo-NMs may serve as a therapeutic strategy for neuroprotection and functional recovery upon ischaemic stroke onset. (C) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
原文链接:- NSTL
- Elsevier
Liu, WeiZhang, HuiDong, XiaoyanSun, Yan...
11页查看更多>>摘要：Photo-oxygenation has become an effective way to inhibit Alzheimer's beta-amyloid protein (A beta) fibrillogenesis, which involves oxidative modification of A beta by photo-oxidants. However, limitations of the current photo-oxidants, such as low biocompatibility and low affinity for A beta, hinder the progression of the photo-oxygenation strategy. Herein, using human serum albumins (HSA) with binding affinity for A beta as a platform, we have fabricated HSA-stabilized gold nanoclusters (AuNCs@HSA) and further modified the AuNCs@HSA with ethylenediamine to create basified HSA (HSA-B)-stabilized AuNCs. The basified composite, AuNCs@HSA-B, showed significantly higher potency on the inhibition of beta-amyloid formation and capability of reactive oxidative species generation than AuNCs@HSA. In addition to the inhibition effect, under near-infrared (NIR) laser irradiation, AuNCs@HSA-B generated singlet oxygen to oxygenate A beta monomers, distinctly alleviating A beta-mediated neurotoxicity at a low concentration. In vivo studies demonstrated that NIR-activated AuNCs@HSA-B promoted the lifespan extension of transgenic C. elegans strain CL2006 by decreasing the A beta burden. This well-designed AuNCs@HSA-B integrates inhibition, A beta targeting, and photo-oxygenation, providing new insights into the development of protein-based photo-oxidant against Alzheimer's beta-amyloid. Statement of significance Alzheimer's disease (AD) has been threatening human health for more than 100 years. Recently, researchers have focused on inhibiting beta-amyloid protein (A beta) aggregation by exploring photo-excited biomaterials, which enable modulation of A beta fibrillization with high spatiotemporal controllability. The present work demonstrates the fabrication of basified human serum albumins (HSA-B)-stabilized gold nanoclusters (AuNCs@HSA-B), and shows the potential of this near-infrared (NIR) laser-activated AuNCs@HSA-B as a photo-oxidant against A beta aggregation by photo-oxygenation. Our work should open a new horizon in the design of protein-based photo-oxidant for treating AD in the future. (C) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
原文链接:- NSTL
- Elsevier
Xu, ShiboChang, LinnaZhao, XingjunHu, Yanan...
15页查看更多>>摘要：Osteoarthritis (OA), a widespread degenerative disease characterized by cartilage destruction, has emerged as a public health challenge in the current aging society. In addition to applied steroids and surgery, near-infrared (NIR) sensitive nano-enzyme for the treatment of osteoarthritis through mitochondrial repair and cartilage protection is attractive and promising. In this study, a NIR sensitive multifunctional heterostructure (EGCG (Epigallocatechin gallate) decorated Au-Ag nano-jars (E@Au-Ag)) was introduced as an enzyme-sensitive active nanoplatform for the treatment of osteoarthritis. Molecular biology results indicated that E@Au-Ag possesses intrinsic properties of anti-oxidative stress and was able to reduce the apoptosis rate of chondrocytes by 83.3%. The area of the intra-articular joint cavity injected with E@Au-Ag can be elevated to 46.6 degrees C under NIR to promote the release of EGCG further to induce cartilage regeneration. X-ray radiography and section staining showed that E@Au-Ag reduced cartilage damage and decreased OARSI scores by approximately 52% after 8 weeks of treatment in a surgically induced OA model. The results demonstrated that this multifunctional enzyme-like nanoplatform with a synergistic NIR sensitive property to facilitate cartilage migration and regeneration repair provides a promising OA treatment strategy.
原文链接:- NSTL
- Elsevier
Kim, JuSeo, Bo-BaeHong, Ki HyunKim, Sung Eun...
12页查看更多>>摘要：The treatment of chronic Achilles tendonitis (AT) often requires prolonged therapy and invasive therapeu-tic methods such as surgery or therapeutic endoscopy. To prevent the progression of chronic AT, exces-sive inflammation must be alleviated at an early stage. Corticosteroids or nonsteroidal anti-inflammatory drugs are generally prescribed to control inflammation; however, the high doses and long therapeutic periods required may lead to serious side effects. Herein, a local injectable poly(organophosphazene) (PPZ) - celecoxib (CXB) nanoparticle (PCNP) hydrogel system with long-term anti-inflammatory effects was developed for the treatment of tendonitis. The amphiphilic structure and thermosensitive mechani-cal properties of PPZ means that the hydrophobic CXB can be easily incorporated into the hydrophobic core to form PCNP at 4 degrees C. Following the injection of PCNP into the AT, PCNP hydrogel formed at body temperature and induced long-term local anti-inflammatory effects via sustained release of the PCNP. The therapeutic effects of the injectable PCNP system can alleviate excessive inflammation during the early stages of tissue damage and boost tissue regeneration. This study suggests that PCNP has significant po-tential as a long-term anti-inflammatory agent through sustained nonsteroidal anti-inflammatory drugs (NSAIDs) delivery and tissue regeneration boosting.& nbsp;Statement of significance & nbsp;In the treatment of Achilles tendinitis, a long-term anti-inflammatory effect is needed to alle-viate excessive inflammation and induce regeneration of the damaged Achilles tendon. Injectable poly(organophosphazene)(PPZ)-celecoxib(CXB) nanoparticles (PCNP) generated a long-term, localized-anti-inflammatory effect in the injected region, which successfully induced the expression of anti-inflammatory cytokines and suppressed pro-inflammatory cytokines, while the PCNPs degraded com-pletely. Accordingly, regeneration of the damaged Achilles tendon was achieved through the long-term anti-inflammatory effect induced by a single PCNP injection. The PCNP system therefore has great poten-tial in long-term NSAIDs delivery for various tissue engineering applications. (C)& nbsp;2022 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc.
原文链接:- NSTL
- Elsevier
Nanda, RajuHazan, ShaniSauer, KatreinAladin, Victoria...
15页查看更多>>摘要：Bone is a fascinating biomaterial composed mostly of type-I collagen fibers as an organic phase, apatite as an inorganic phase, and water molecules residing at the interfaces between these phases. They are hierarchically organized with minor constituents such as non-collagenous proteins, citrate ions and glycosaminoglycans into a composite structure that is mechanically durable yet contains enough porosity to accommodate cells and blood vessels. The nanometer scale organization of the collagen fibrous structure and the mineral constituents in bone were recently extensively scrutinized. However, molecular details at the lowest hierarchical level still need to be unraveled to better understand the exact atomic-level arrangement of all these important components in the context of the integral structure of the bone. In this report, we unfold some of the molecular characteristics differentiating between two load-bearing (cleithrum) bones, one from sturgeon fish, where the matrix contains osteocytes and one from pike fish where the bone tissue is devoid of these bone cells. Using enhanced solid-state NMR measurements, we underpin disparities in the collagen fibril structure and dynamics, the mineral phases, the citrate content at the organic-inorganic interface and water penetrability in the two bones. These findings suggest that different strategies are undertaken in the erection of the mineral-organic interfaces in various bones characterized by dissimilar osteogenesis or remodeling pathways and may have implications for the mechanical properties of the particular bone.& nbsp;Statement of significance & nbsp;Bone boasts unique interactions between collagen fibers and mineral phases through interfaces holding together this bio-composite structure. Over evolution, fish have gone from mineralizing their bones aided by certain bone cells called osteocytes, like tetrapod, to mineralization without these cells. Here, we report atomic level differences in collagen fiber cross linking and organization, porosity of the mineral phases and content of citrate molecules at the bio-mineral interface in bones from modern versus ancient fish. The dissimilar structural features may suggest disparate mechanical properties for the two bones. Fundamental level understanding of the organic and inorganic components in bone and the interfacial interactions holding them together is essential for successful bone repair and for treating better tissue pathologies. (C) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
原文链接:- NSTL
- Elsevier
Kohn, StephanLeichsenring, KayMorales-Orcajo, EnriqueBoel, Markus...
11页查看更多>>摘要：Skeletal muscle tissue shows a clear asymmetry with regard to the passive stresses under tensile and compressive deformation, referred to as tension-compression asymmetry (TCA). The present study is the first one reporting on TCA at different length scales, associated with muscle tissue and muscle fibres, respectively. This allows for the first time the comparison of TCA between the tissue and one of its individual components, and thus to identify the length scale at which this phenomenon originates. Not only the passive stress-stretch characteristics were recorded, but also the volume changes during the axial tension and compression experiments. The study reveals clear differences in the characteristics of TCA between fibres and tissue. At tissue level TCA increases non-linearly with increasing deformation and the ratio of tensile to compressive stresses at the same magnitude of strain reaches a value of approximately 130 at 13.5% deformation. At fibre level instead it initially drops to a value of 6 and then rises again to a TCA of 14. At a deformation of 13.5%, the tensile stress is about 6 times higher. Thus, TCA is about 22 times more expressed at tissue than fibre scale. Moreover, the analysis of volume changes revealed little compressibility at tissue scale whereas at fibre level, especially under compressive stress, the volume decreases significantly. The data collected in this study suggests that the extracellular matrix has a distinct role in amplifying the TCA, and leads to more incompressible tissue behaviour. Statement of significance This article analyses and compares for the first time the tension-compression asymmetry (TCA) displayed by skeletal muscle at tissue and fibre scale. In addition, the volume changes of tissue and fibre specimens with application of passive tensile and compressive loads are studied. The study identifies a key role of the extracellular matrix in establishing the mechanical response of skeletal muscle tissue: It contributes significantly to the passive stress, it is responsible for the major part of tissue-scale TCA and, most probably, prevents/balances the volume changes of muscle fibres during deformation. These new results thus shed light on the origin of TCA and provide new information to be used in microstructure-based approaches to model and simulate skeletal muscle tissue.(c) 2022 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
原文链接:- NSTL
- Elsevier
Zwaans, Bernadette M. M.Grobbel, MarissaCarabulea, Alexander L.Lamb, Laura E....
9页查看更多>>摘要：Radiation cystitis, a long-term bladder defect due to pelvic radiation therapy, results in lower urinary tract symptoms, such as urinary frequency and nocturia, suggestive of compromised bladder compliance. The goal of this study was to identify alterations to the mechanical behavior of the urinary bladder extracel-lular matrix of a murine model of radiation cystitis, at 3 and 6 months after radiation exposure. The re-sults of this study demonstrated that the extracellular matrix of irradiated bladders was significantly less distensible when compared to age matching controls. These findings coincided with functional bladder changes, including increased number of voids and decreased voided volume. Both mechanical and func-tional changes were apparent at 3 months post-irradiation and were statistically significant at 6 months, demonstrating the progressive nature of radiation cystitis. Overall, the results of this study indicate that irradiation exposure changes both the mechanical and physiological properties of the bladder.Statement of significance In humans, radiation cystitis results in lower urinary tract symptoms, such as urinary frequency and noc-turia, suggestive of compromised bladder compliance. This pathology can significantly affect recovery and quality of life for cancer survivors. Gaining knowledge about how alterations to the mechanical behavior of the urinary bladder extracellular matrix can affect urinary function will have a significant impact on this population. The results of this study demonstrated that the extracellular matrix of irradiated bladders was significantly less distensible when compared to age matching controls, in a mouse model of radiation cystitis. These findings were accompanied by functional voiding changes, including increased number of voids and decreased voided volume. The results of this study uncovered that irradiation exposure changes the mechanical and physiological properties of the bladder.(c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
原文链接:- NSTL
- Elsevier
Serr, AnneroseWittmer, AnnetteBohner, MarcSeidenstuecker, Michael...
12页查看更多>>摘要：The aim of this work was to establish an organ model for staphylococcal infection of human bone samples and to investigate the influence and efficacy of a microporous beta-tricalcium phosphate ceramic (beta-TCP, RMS Foundation) loaded with hydrogels (alginate, alginate-di-aldehyde (ADA)-gelatin) and clindamycin on infected human bone tissue over a period of 28 days. For this purpose, human tibia plateaus, collected during total knee replacement surgery, were used as a source of bone material. Samples were infected with S. aureus ATCC29213 and treated with differently loaded beta-TCP composites (alginate + /-clindamycin, ADA-gelatin + /-clindamycin, unloaded). The loading of the composites was carried out by means of a flow chamber. The infection was observed for 28 days, quantifying bacteria in the medium and the osseus material on day 1, 7, 14, 21 and 28. All samples were histologically processed for bone vitality evaluation. Bone infection could be consistently performed within the organ model. In addition, a strong reduction in bacterial counts was recorded in the groups treated with ADA-gelatin + clindamycin and alginate + clindamycin, while the bacterial count in the control groups remained constant. No significant differences between groups could be observed in the number of lacunae filled with osteocytes suggesting no differences in bone vitality among groups. In an ex-vivo human bone infection model, over a period of 28 days bacterial growth could be reduced by treatment with ADA-Gel + CLI and ALG + CLI-releasing beta-TCP composites. This could be relevant for its clinical use. Further work will be necessary to improve the loading of beta-TCP and the bone infection organ model itself.& nbsp;Statement of Significance & nbsp;The common treatment of bone infections is debridement and systemic administration of antibiotics. In some cases, antibiotic-containing carriers are already used, but these must be removed again. Our work is intended to show another treatment option. The scaffold we have developed, made of a calcium phosphate ceramic and a hydrogel as the active substance carrier, can, in addition to releasing the active substance, also assume a load-bearing function of the bone and is biodegradable. In addition, the model we developed can also be used for the analysis and treatment of bone infections other than those of the musculoskeletal system. More importantly, it can also serve as a substitute for previously used animal experiments. (C)& nbsp;2022 Published by Elsevier Ltd on behalf of Acta Materialia Inc.
原文链接:- NSTL
- Elsevier
Hu, XingyuYang, ZiyangTian, WeidongLiang, Xi...
16页查看更多>>摘要：A B S T R A C T Combined injectable cell-laden microspheres and angiogenesis approaches are promising for functional vascularized endodontic regeneration. However, advanced microsphere designs and production techniques that benefit practical applications are rarely developed. Herein, gelatin methacryloyl (GelMA)-alginate core-shell microcapsules were fabricated to co-encapsulate human dental pulp stem cells (hDPSCs) and human umbilical vein endothelial cells (HUVECs) based on a coaxial electrostatic microdroplet technique. This technique enables high-throughput production, convenient collection, and minimal material waste. The average diameter of core-shell microcapsules was-359 mu m, and that of GelMA cores was-278 mu m. There were higher proliferation rates for hDPSCs and HUVECs co-encapsulated in the GelMA cores than for hDPSCs or HUVECs monoculture group. HUVECs assembled to form 3D capillary-like networks in co-culture microcapsules. Moreover, HUVECs promoted the osteo/odontogenic differentiation of hDP-SCs in microcapsules. After 14 days of cultivation, prevascularized microtissues formed in microcapsules that contained abundant deposited extracellular matrix (ECM); no microcapsule aggregation occurred. In vivo studies confirmed that better microvessel formation and pulp-like tissue regeneration occurred in the co-culture group than in hDPSCs group. Thus, an effective platform for prevascularization microtissue preparation was proposed and showed great promise in endodontic regeneration and tissue engineering applications.
原文链接:- NSTL
- Elsevier
