Advanced healthcare materials




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سفارش

Thermochromic Polyvinyl Alcohol-Iodine Hydrogels with Safe Threshold Temperature for Infectious Wound Healing (Adv. Healthcare Mater. 18/2021)

Zhaohua Miao,Yanbin Sun,Zhenchao Tao,Yu Chen,Yan Ma,Dongdong Zhu,Xiang Huang,Zhengbao Zha,

doi : 10.1002/adhm.202170081

Volume 10, Issue 18 2170081

In article number 2100722 by Zhengbao Zha and co-workers, a blue polyvinyl alcohol-iodine hydrogel with thermochromic and laser-triggered liquefaction properties, originated from the dynamic interaction between iodine and polyvinyl alcohol, is explored as an effective alternative to conventional iodophor for safe and controllable management of multidrug-resistance bacterial-infected open wounds.

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Emerging Technologies for In Vitro Inhalation Toxicology (Adv. Healthcare Mater. 18/2021)

Ajay Vikram Singh,Anthony Romeo,Kassandra Scott,Sandra Wagener,Lars Leibrock,Peter Laux,Andreas Luch,Pranali Kerkar,Shidin Balakrishnan,Sarada Prasad Dakua,Byung-Wook Park,

doi : 10.1002/adhm.202170082

Volume 10, Issue 18 2170082

In article number 2100633 by Ajay Vikram Singh, Byung-Wook Park, and co-workers, a systematic approach is taken to discuss the bottleneck, pros and cons of current technologies pertaining to organ-on-a-chip systems for inhalation toxicology. Design processes inspired from soft robotics actuation with attention to the inhalation exposure, lung cells, and materials used are presented.

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Sex-Specific Response to Combinations of Shear Stress and Substrate Stiffness by Endothelial Cells In Vitro (Adv. Healthcare Mater. 18/2021)

Bryan D. James,Josephine B. Allen,

doi : 10.1002/adhm.202170084

Volume 10, Issue 18 2170084

The work presented in article number 2100735 by Bryan D. James and Josephine B. Allen highlights the differential response of male and female endothelial cells to microenvironments of physiological shear stress and substrates stiffness. In terms of cell spreading and YAP1 expression, conditions where male endothelial cells showed sensitivity to mechanical stimulation, female endothelial cells were largely insensitive. These insights reiterate that biological sex is an important variable to consider when designing precision biomaterials.

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Masthead: (Adv. Healthcare Mater. 18/2021)

doi : 10.1002/adhm.202170083

Volume 10, Issue 18 2170083

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Monodispersed Bioactive Glass Nanoclusters with Ultralarge Pores and Intrinsic Exceptionally High miRNA Loading for Efficiently Enhancing Bone Regeneration

Yumeng Xue,Yi Guo,Meng Yu,Min Wang,Peter X. Ma,Bo Lei,

doi : 10.1002/adhm.202101616

Volume 10, Issue 18 2101616

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Tumor Associated Macrophages and TAMs-Based Anti-Tumor Nanomedicines

Yuxi Cheng,Siyang Song,Peiyao Wu,Bochen Lyu,Mengmeng Qin,Yanan Sun,Aning Sun,Limin Mu,Fei Xu,Lu Zhang,Jiancheng Wang,Qiang Zhang,

doi : 10.1002/adhm.202100590

Volume 10, Issue 18 2100590

As an important part of tumor microenvironment, tumor associated macrophages (TAMs) play a vital role in the occurrence, development, invasion, and metastasis of many malignant tumors and can significantly promote the formation of tumor blood vessels and lymphatic vessels, hence TAMs are greatly associated with poor prognosis. The research on nanomedicine has achieved huge progress, and nano-drugs have been widely utilized to treat various diseases through different mechanisms. Therefore, developing nano-drugs that are based on TAMs-associated anti-tumor mechanisms to effectively suppress tumor growth is expected to be a promising research filed. This paper introduces relevant information about TAMs in terms of their origin, and their roles in tumor genesis, development and metastasis. Furthermore, TAMs-related anti-tumor nano-drugs are summarized. Specifically, a wide range of nano-drugs targeting at TAMs are introduced, and categorized according to their therapeutic mechanisms toward tumors. Additionally, various nano delivery platforms using TAMs as cell carriers which aim at inhibiting tumor growth are reviewed. These two parts elucidate that the exploration of nanomedicine is essential to the study on TAMs-related anti-tumor strategies. This review is also intended to provide novel ideas for in-depth investigation on anti-tumor molecular mechanisms and nano-drug delivery systems based on TAMs.

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The Action-Networks of Nanosilver: Bridging the Gap between Material and Biology

Huiliang Cao,Hui Qin,Yongsheng Li,Klaus D. Jandt,

doi : 10.1002/adhm.202100619

Volume 10, Issue 18 2100619

The emergence of nanosilver (silver in nanoscale shapes and their assemblies) benefits the landscape of modern healthcare; however, this brings about concerns over its safety issues associated with an ultrasmall size and high mobility. By reviewing previous reporting details about the synthesis and characterization of nanosilver and its biological responses, a gap between materials synthesis and their biomedical uses is characterized by the insufficient understanding of the interacting and interplaying nanoscale actions of silver. To improve reporting quality and advance clinical translations, it is suggested that researchers have a comprehensive recognition of the “Indications for use” before designing innovative nanosilver-based materials and an “Action-network” concept addressing the acting range and strength of those nanoscale actions is implemented. Although this discussion is specific to nanosilver, the idea of “Indications for use” centered design and synthesis is generally applicable to other biomedical nanomaterials.

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Emerging Technologies for In Vitro Inhalation Toxicology

Ajay Vikram Singh,Anthony Romeo,Kassandra Scott,Sandra Wagener,Lars Leibrock,Peter Laux,Andreas Luch,Pranali Kerkar,Shidin Balakrishnan,Sarada Prasad Dakua,Byung-Wook Park,

doi : 10.1002/adhm.202100633

Volume 10, Issue 18 2100633

Respiratory toxicology remains a major research area in the 21st century since current scenario of airborne viral infection transmission and pollutant inhalation is expected to raise the annual morbidity beyond 2 million. Clinical and epidemiological research connecting human exposure to air contaminants to understand adverse pulmonary health outcomes is, therefore, an immediate subject of human health assessment. Important observations in defining systemic effects of environmental contaminants on inhalation metabolic dysfunction, liver health, and gastrointestinal tract have been well explored with in vivo models. In this review, a framework is provided, a paradigm is established about inhalation toxicity testing in vitro, and a brief overview of breathing Lungs-on-Chip (LoC) as design concepts is given. The optimized bioengineering approaches and microfluidics with their fundamental pros, and cons are presented. There are different strategies that researchers apply to inhalation toxicity studies to assess a variety of inhalable substances and relevant LoC approaches. A case study from published literature and frame arguments about reproducibility as well as in vitro/in vivo correlations are discussed. Finally, the opportunities and challenges in soft robotics, systems inhalation toxicology approach integrating bioengineering, machine learning, and artificial intelligence to address a multitude model for future toxicology are discussed.

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Polymeric Micro/Nanomotors and Their Biomedical Applications

Ziying Liang,Yingfeng Tu,Fei Peng,

doi : 10.1002/adhm.202100720

Volume 10, Issue 18 2100720

Since their naissance in the 2000s, various micro or nanomotors with powerful functions have been proposed. Among them, polymer-based micro or nanomotors stand out for the easy processing and facile functionalization, holding immense potential for bioapplications. In this review, fabrication of polymer-based micro or nanomotors and their applications in biomedical areas are covered. Classic manufacturing approaches as well as cutting-edge techniques are discussed with representative works highlighted. Current challenges and future prospects are presented in the hope of pointing new research directions to facilitate practical translations of micro/nanomotors.

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Thermochromic Polyvinyl Alcohol-Iodine Hydrogels with Safe Threshold Temperature for Infectious Wound Healing

Zhaohua Miao,Yanbin Sun,Zhenchao Tao,Yu Chen,Yan Ma,Dongdong Zhu,Xiang Huang,Zhengbao Zha,

doi : 10.1002/adhm.202100722

Volume 10, Issue 18 2100722

Iodophor (povidone-iodine) has been widely used for antibacterial applications in the clinic. Yet, limited progress in the field of iodine-based bactericides has been achieved since the invention of iodophor. Herein, a blue polyvinyl alcohol-iodine (PAI) complex-based antibacterial hydrogel is explored as a new generation of biocompatible iodine-based bactericides. The obtained PAI hydrogel maintains laser triggered liquefaction, thermochromic, and photothermal features for highly efficient elimination of bacteria. In vitro antibacterial test reveals that the relative bacteria viabilities of Escherichia coli (E.coli) and methicillin-resistant Staphylococcus aureus (MRSA) incubated with PAI hydrogel are only 8% and 3.8%, respectively. Upon single injection of the PAI hydrogel, MRSA-infected open wounds can be efficiently healed in only 5 days, and the healing speed is further accelerated by laser irradiation due to the dynamic interaction between iodine and polyvinyl alcohol, causing up to ?29% of wound area being closed on day 1. In addition, a safe threshold temperature of skin scald (?45 °C) emerges for PAI hydrogels because of thermochromic properties, avoiding thermal injuries during irradiation. In addition, no observed toxicity or skin irritation is observed for the PAI hydrogel. This work expands the category of iodine-based bactericides for safe and controllable management of infected wounds.

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Sex-Specific Response to Combinations of Shear Stress and Substrate Stiffness by Endothelial Cells In Vitro

Bryan D. James,Josephine B. Allen,

doi : 10.1002/adhm.202100735

Volume 10, Issue 18 2100735

By using a full factorial design of experiment, the combinatorial effects of biological sex, shear stress, and substrate stiffness on human umbilical vein endothelial cell (HUVEC) spreading and Yes-associated protein 1 (YAP1) activity are able to be efficiently evaluated. Within the range of shear stress (0.5–1.5 Pa) and substrate stiffness (10–100 kPa), male HUVECs are smaller than female HUVECs. Only with sufficient mechanical stimulation do they spread to a similar size. More importantly, YAP1 nuclear localization in female HUVECs is invariant to mechanical stimulation within the range of tested conditions whereas for male HUVECs it increases nonlinearly with increasing shear stress and substrate stiffness. The sex-specific response of HUVECs to combinations of shear stress and substrate stiffness reinforces the need to include sex as a biological variable and multiple mechanical stimuli in experiments, informs the design of precision biomaterials, and offers insight for understanding cardiovascular disease sexual dimorphisms. Moreover, here it is illustrated that different complex mechanical microenvironments can lead to sex-specific phenotypes and sex invariant phenotypes in cultured endothelial cells.

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A Conformable, Gas-Permeable, and Transparent Skin-Like Micromesh Architecture for Glucose Monitoring

Ya-Lei Li,Yan-Hua Liu,Lin-Sen Chen,Jian-Long Xu,

doi : 10.1002/adhm.202100046

Volume 10, Issue 18 2100046

Monitoring the concentration of useful biomarkers via electronic skins (e-skins) is highly important for the development of wearable health management systems. While some biosensor e-skins with high flexibility, sensitivity, and stability have been developed, little attention has been paid to their long-term comfortability and optical transparency. Here, a conformable, gas permeable, and transparent skin-like Cu2O@Ni micromesh structural glucose monitoring patch is reported. With its self-supporting micromesh structure, the skin-like glucose monitoring patch exhibits excellent shape conformability, high gas permeability, and high optical transmittance. The skin-like glucose biosensor achieves real-time monitoring of glucose concentrations with high sensitivity (15?420 µA cm?2mM?1), low detection limit (50 nM), fast response time (?2 s), high selectivity, and long-term stability. These desirable performance properties arise from the synergistic effects of the self-supporting micromesh configuration, high conductivity of the metallic Ni micromesh, and high electrocatalytic activities of the Cu2O toward glucose. This work presents a versatile and efficient strategy for constructing conformable, gas permeable, and transparent biosensor e-skins with excellent practicability towards wearable electronics.

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Substance P/Heparin-Conjugated PLCL Mitigate Acute Gliosis on Neural Implants and Improve Neuronal Regeneration via Recruitment of Neural Stem Cells

Donghak Kim,DoYeun Park,Tae Hee Kim,Justin J. Chung,Youngmee Jung,Soo Hyun Kim,

doi : 10.1002/adhm.202100107

Volume 10, Issue 18 2100107

The inflammatory host tissue response, characterized by gliosis and neuronal death at the neural interface, limits signal transmission and longevity of the neural probe. Substance P induces an anti-inflammatory response and neuronal regeneration and recruits endogenous stem cells. Heparin prevents nonspecific protein adsorption, suppresses the inflammatory response, and is beneficial to neuronal behavior. Poly(l-lactide-co-?-caprolactone) (PLCL) is a soft and flexible polymer, and PLCL covalently conjugated with biomolecules has been widely used in tissue engineering. Coatings of heparin-conjugated PLCL (Hep-PLCL), substance P-conjugated PLCL (SP-PLCL), and heparin/substance P-conjugated PLCL (Hep/SP-PLCL) reduced the adhesion of astrocytes and fibroblasts and improved neuronal adhesion and neurite development compared to bare glass. The effects of these coatings are evaluated using immunohistochemistry analysis after implantation of coated stainless steel probes in rat brain for 1 week. In particular, Hep/SP-PLCL coating reduced the activation of microglia and astrocytes, the neuronal degeneration caused by inflammation, and indicated a potential for neuronal regeneration at the tissue–device interface. Suppression of the acute host tissue response by coating Hep/SP-PLCL could lead to improved functionality of the neural prosthesis.

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Enhancing the Stability of COVID-19 Serological Assay through Metal–Organic Framework Encapsulation

Yixuan Wang,Zheyu Wang,Prashant Gupta,Jeremiah J. Morrissey,Rajesh R. Naik,Srikanth Singamaneni,

doi : 10.1002/adhm.202100410

Volume 10, Issue 18 2100410

Enzyme-linked immunosorbent assay is widely utilized in serologic assays, including COVID-19, for the detection and quantification of antibodies against SARS-CoV-2. However, due to the limited stability of the diagnostic reagents (e.g., antigens serving as biorecognition elements) and biospecimens, temperature-controlled storage and handling conditions are critical. This limitation among others makes biodiagnostics in resource-limited settings, where refrigeration and electricity are inaccessible or unreliable, particularly challenging. In this work, metal–organic framework encapsulation is demonstrated as a simple and effective method to preserve the conformational epitopes of antigens immobilized on microtiter plate under non-refrigerated storage conditions. It is demonstrated that in situ growth of zeolitic imidazolate framework-90 (ZIF-90) renders excellent stability to surface-bound SARS-CoV-2 antigens, thereby maintaining the assay performance under elevated temperature (40 °C) for up to 4 weeks. As a complementary method, the preservation of plasma samples from COVID-19 patients using ZIF-90 encapsulation is also demonstrated. The energy-efficient approach demonstrated here will not only alleviate the financial burden associated with cold-chain transportation, but also improve the disease surveillance in resource-limited settings with more reliable clinical data.

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Effect of Particle Size and Surface Chemistry of Photon-Upconversion Nanoparticles on Analog and Digital Immunoassays for Cardiac Troponin

Julian C. Brandmeier,Kirsti Raiko,Zden?k Farka,Riikka Peltomaa,Matthias J. Mickert,Antonín Hlavá?ek,Petr Skládal,Tero Soukka,Hans H. Gorris,

doi : 10.1002/adhm.202100506

Volume 10, Issue 18 2100506

Sensitive immunoassays are required for troponin, a low-abundance cardiac biomarker in blood. In contrast to conventional (analog) assays that measure the integrated signal of thousands of molecules, digital assays are based on counting individual biomarker molecules. Photon-upconversion nanoparticles (UCNP) are an excellent nanomaterial for labeling and detecting single biomarker molecules because their unique anti-Stokes emission avoids optical interference, and single nanoparticles can be reliably distinguished from the background signal. Here, the effect of the surface architecture and size of UCNP labels on the performance of upconversion-linked immunosorbent assays (ULISA) is critically assessed. The size, brightness, and surface architecture of UCNP labels are more important for measuring low troponin concentrations in human plasma than changing from an analog to a digital detection mode. Both detection modes result approximately in the same assay sensitivity, reaching a limit of detection (LOD) of 10 pg mL?1 in plasma, which is in the range of troponin concentrations found in the blood of healthy individuals.

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A Microfluidic Model Artery for Studying the Mechanobiology of Endothelial Cells

Hyeonji Yu,Dongwon Kang,Minji Whang,Taeyoung Kim,Jungwook Kim,

doi : 10.1002/adhm.202100508

Volume 10, Issue 18 2100508

Recent vascular mechanobiology studies find that endothelial cells (ECs) convert multiple mechanical forces into functional responses in a nonadditive way, suggesting that signaling pathways such as those regulating cytoskeleton may be shared among the processes of converting individual forces. However, previous in vitro EC-culture platforms are inherent with extraneous mechanical components, which may saturate or insufficiently activate the shared signaling pathways and accordingly, may misguide EC mechanobiological responses being investigated. Here, a more physiologically relevant model artery is reported that accurately reproduces most of the mechanical forces found in vivo, which can be individually varied in any combination to pathological levels to achieve diseased states. Arterial geometries of normal and diseased states are also realized. By mimicking mechanical microenvironments of early-stage atherosclerosis, it is demonstrated that the elevated levels of the different types of stress experienced by ECs strongly correlate with the disruption of barrier integrity, suggesting that boundaries of an initial lesion could be sites for efficient disease progression.

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A Honeycomb-Like Bismuth/Manganese Oxide Nanoparticle with Mutual Reinforcement of Internal and External Response for Triple-Negative Breast Cancer Targeted Therapy

Xingyi Xu,Rongyuan Zhang,Xianfeng Yang,Yao Lu,Zhongmin Yang,Mingying Peng,Zhijun Ma,Ju Jiao,Lihua Li,

doi : 10.1002/adhm.202100518

Volume 10, Issue 18 2100518

Triple-negative breast cancer (TNBC) exhibits aggressive behavior and high levels of metastasis owing to its complex heterogeneous structure and lack of specific receptors. Here, tumor cell membrane (CM)-coated bismuth/manganese oxide nanoparticles (NPs) with high indocyanine green (ICG) payload up to 50.6 wt% (mBMNI NPs) for targeted TNBC therapy are constructed. The extra-high drug load Bi@Bi2O3@MnOx NPs (honey-comb like structure) are formed by Kirkendall effect and electrostatic attraction. After modified with CM, they can home into tumor sites precisely, where they respond to internal overexpressed glutathione (GSH), releasing Mn2+ for chemodynamic therapy (CDT) with GSH depletion, while H2O2 degrades into O2 enabling relief of tumor hypoxia. In response to external near-infrared irradiation, mBMNI NPs intelligently generate vigorous heat and single oxygen (1O2) for photothermal therapy (PTT) and photodynamic therapy (PDT) owing to high load. Importantly, O2 production and GSH consumption during the internal response reinforce external PDT, while the heat generated through PTT during the external response promotes internal CDT. The honeycomb-like structure with high ICG load and mutual reinforcement between internal and external response results in excellent therapeutic effects against TNBC.

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Promoting Long-Term Cultivation of Motor Neurons for 3D Neuromuscular Junction Formation of 3D In Vitro Using Central-Nervous-Tissue-Derived Bioink

Jeong Sik Kong,Xuan Huang,Yeong-Jin Choi,Hee-Gyeong Yi,Junsu Kang,Sejin Kim,Jongmin Kim,Hyungseok Lee,Yeri Alice Rim,Ji Hyeon Ju,Wan Kyun Chung,Clifford J. Woolf,Jinah Jang,Dong-Woo Cho,

doi : 10.1002/adhm.202100581

Volume 10, Issue 18 2100581

3D cell printing technology is in the spotlight for producing 3D tissue or organ constructs useful for various medical applications. In printing of neuromuscular tissue, a bioink satisfying all the requirements is a challenging issue. Gel integrity and motor neuron activity are two major characters because a harmonious combination of extracellular materials essential to motor neuron activity consists of disadvantages in mechanical properties. Here, a method for fabrication of 3D neuromuscular tissue is presented using a porcine central nervous system tissue decellularized extracellular matrix (CNSdECM) bioink. CNSdECM retains CNS tissue-specific extracellular molecules, provides rheological properties crucial for extrusion-based 3D cell printing, and reveals positive effects on the growth and maturity of axons of motor neurons compared with Matrigel. It also allows long-term cultivation of human-induced-pluripotent-stem-cell-derived lower motor neurons and sufficiently supports their cellular behavior to carry motor signals to muscle fibers. CNSdECM bioink holds great promise for producing a tissue-engineered motor system using 3D cell printing.

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Self-Cycling Free Radical Generator from LDH-Based Nanohybrids for Ferroptosis-Enhanced Chemodynamic Therapy

Xueting Yang,Li Wang,Shuaitian Guo,Ran Li,Fangzhen Tian,Shanyue Guan,Shuyun Zhou,Jun Lu,

doi : 10.1002/adhm.202100539

Volume 10, Issue 18 2100539

Nonapoptotic ferroptosis has been a novel form of programmed cell death, which provides a new solution to enrich the anticancer treatment efficacy of traditional apoptotic therapeutic modality. Herein, a novel nanohybrid is designed by loading the PEG-encapsulated Artemisinin (denoted as A@P) on the ultrathin MgFe-LDH nanosheets (denoted as uLDHs) for improved chemodynamic therapy (CDT). The A@P/uLDHs cannot only realize the self-assembly between the Art and carrier but also be regarded as free radical generator. A comprehensive mechanistic study suggests that this unique A@P/uLDHs is able to in situ activate Art and self-cycling generate toxic C-centered free radical inside the cancer cells, without depending on abundant H2O2, accompanied with diminished cancerous antioxidation by depleting glutathione (GSH). The accumulation of ROS and depletion of GSH can further oxidize unsaturated fatty acid to generate lipid peroxide, whose overexpression can induce cell ferroptosis accompanied by cellular iron homeostasis turbulence. Both in vitro and in vivo results exhibit that A@P/uLDHs are an efficient nanoagent for highly efficient ferroptosis-enhanced CDT treatment. This work imparts the promising new visions about the ferroptosis-enhanced CDT via fine regulation of material design for improved cancer treatments.

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A Deep Eutectic Solvent-Based Approach to Intravenous Formulation

Jayoung Kim,Yujie Shi,Christopher J. Kwon,Yongsheng Gao,Samir Mitragotri,

doi : 10.1002/adhm.202100585

Volume 10, Issue 18 2100585

Clinically viable formulations of hydrophobic drugs, for example, chemotherapeutics, require strategies to promote sufficient drug solubilization. However, such strategies often involve the use of organic solvents that pose a significant risk in generating toxic, unstable products. Using verteporfin as a drug, a deep eutectic solvent (DES)-based approach to solvate drugs in a simple one-step process is reported. Lipoidal DES composed of choline and oleate is used to successfully solvate verteporfin, resulting in stable sub-100 nm nanocomplexes. The nanocomplexes successfully demonstrate efficient cellular uptake as well as retention, tumor spheroid penetration, and tumor accumulation in vivo. Systemic administration of the formulation significantly inhibits the primary tumor growth and its lung metastasis in the orthotopic 4T1 murine breast tumor model. Collectively, biocompatible DES shows great potential as a novel material for intravenous formulation of chemotherapeutics.

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An Injectable Multifunctional Dual-Phase Bead-Reinforced Gelatin Matrix Permissive of Mesenchymal Stem Cell Infiltration for Musculoskeletal Soft Tissue Repair

Dajiang Du,Zhen Liu,Wanting Niu,Ding Weng,Teck Chuan Lim,Motoichi Kurisawa,Myron Spector,

doi : 10.1002/adhm.202100626

Volume 10, Issue 18 2100626

This study develops a novel strategy for regenerative therapy of musculoskeletal soft tissue defects using a dual-phase multifunctional injectable gelatin-hydroxyphenyl propionic acid (Gtn-HPA) composite. The dual-phase gel consists of stiff, degradation-resistant, ?2-mm diameter spherical beads made from 8 wt% Gtn-HPA in a 2 wt% Gtn-HPA matrix. The results of a 3D migration assay show that both the cell number and migration distance in the dual-phase gel system are comparable with the 2 wt% mono-phase Gtn-HPA, but notably significantly higher than for 8 wt% mono-phase Gtn-HPA (into which few cells migrated). The results also show that the dual phase gel system has degradation resistance and a prolonged growth factor release profile comparable with 8 wt% mono-phase Gtn-HPA. In addition, the compressive modulus of the 2 wt% dual-phase gel system incorporating the 8 wt% bead phase is nearly four-fold higher than the 2 wt% mono-phase gel (5.3 ± 0.4 kPa versus 1.5 ± 0.06 kPa). This novel injectable dual-phase Gtn-HPA composite thus combines the advantages of low-concentration Gtn-HPA (cell migration) with high-concentration Gtn-HPA (stiffness, degradation resistance, slower chemical release kinetics) to facilitate effective reparative/regenerative processes in musculoskeletal soft tissue.

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Quantitative Photothermal Characterization with Bioprinted 3D Complex Tissue Constructs for Early-Stage Breast Cancer Therapy Using Gold Nanorods

Ki-Hwan Nam,Chan Bae Jeong,HyeMi Kim,Minjun Ahn,Sung-Jun Ahn,Hwan Hur,Dong Uk Kim,Jinah Jang,Hui-Jeong Gwon,Youn-Mook Lim,Dong-Woo Cho,Kye-Sung Lee,Ji Yong Bae,Ki Soo Chang,

doi : 10.1002/adhm.202100636

Volume 10, Issue 18 2100636

Plasmonic photothermal therapy (PPTT) using gold nanoparticles (AuNPs) has shown great potential for use in selective tumor treatment, because the AuNPs can generate destructive heat preferentially upon irradiation. However, PPTT using AuNPs has not been added to practice, owing to insufficient heating methods and tissue temperature measurement techniques, leading to unreliable and inaccurate treatments. Because the photothermal properties of AuNPs vary with laser power, particle optical density, and tissue depth, the accurate prediction of heat generation is indispensable for clinical treatment. In this report, bioprinted 3D complex tissue constructs comprising processed gel obtained from porcine skin and human decellularized adipose tissue are presented for characterization of the photothermal properties of gold nanorods (AuNRs) having an aspect ratio of 3.7 irradiated by a near-infrared laser. Moreover, an analytical function is suggested for achieving PPTT that can cause thermal damage selectively on early-stage human breast cancer by regulating the heat generation of the AuNRs in the tissue.

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3D Printing of Microgel Scaffolds with Tunable Void Fraction to Promote Cell Infiltration

Alexis J. Seymour,Sungchul Shin,Sarah C. Heilshorn,

doi : 10.1002/adhm.202100644

Volume 10, Issue 18 2100644

Granular, microgel-based materials have garnered interest as promising tissue engineering scaffolds due to their inherent porosity, which can promote cell infiltration. Adapting these materials for 3D bioprinting, while maintaining sufficient void space to enable cell migration, can be challenging, since the rheological properties that determine printability are strongly influenced by microgel packing and void fraction. In this work, a strategy is proposed to decouple printability and void fraction by blending UV-crosslinkable gelatin methacryloyl (GelMA) microgels with sacrificial gelatin microgels to form composite inks. It is observed that inks with an apparent viscosity greater than ?100 Pa s (corresponding to microgel concentrations ?5 wt%) have rheological properties that enable extrusion-based printing of multilayered structures in air. By altering the ratio of GelMA to sacrificial gelatin microgels, while holding total concentration constant at 6 wt%, a family of GelMA:gelatin microgel inks is created that allows for tuning of void fraction from 0.20 to 0.57. Furthermore, human umbilical vein endothelial cells (HUVEC) seeded onto printed constructs are observed to migrate into granular inks in a void fraction-dependent manner. Thus, the family of microgel inks holds promise for use in 3D printing and tissue engineering applications that rely upon cell infiltration.

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Sub 5 nm Gd3+–Hemoporfin Framework Nanodots for Augmented Sonodynamic Theranostics and Fast Renal Clearance

Peng Geng,Nuo Yu,Xiaohan Liu,Qin Zhu,Mei Wen,Qian Ren,Pu Qiu,Haijun Zhang,Maoquan Li,Zhigang Chen,

doi : 10.1002/adhm.202100703

Volume 10, Issue 18 2100703

Metal–organic nanomaterials have emerged as promising therapeutic agents to produce reactive oxygen species (ROS) under ultrasound (US) or light irradiation for tumor treatments. However, their relatively large sizes (ranging from tens to hundreds of nanometers) usually lead to low ROS utilization and body metabolism, thus enlarging their long-term toxicity and low therapeutic effect. To solve these shortcomings, herein the ultrasmall Gd3+–hemoporfin framework nanodots (GdHF-NDs? ?5 nm) is reported as efficient nano-sonosensitizers. Compared with GdHF aggregation (GdHF-A, ?400 nm), the ultrasmall GdHF-NDs generate 2.3-fold toxic ROS amount under similar conditions, due to shorter diffusion path and larger relative specific surface area. When the GdHF-NDs dispersion is introvenously injected into tumor-bearing mouse, they are accumulated within tumors to provide high magnetic resonance imaging (MRI) contrast. Under US irradiation, the GdHF-NDs achieve a better sonodynamic therapeutic efficacy for tumors, compared with that from GdHF-A. More importantly, owing to ultrasmall size, most of GdHF-NDs can be rapidly cleared through the renal pathway. Therefore, GdHF-NDs can be used as a biosafety and high-performance sonodynamic agent for cancer theranostics.

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Synergistical Starvation and Chemo-Dynamic Therapy for Combating Multidrug-Resistant Bacteria and Accelerating Diabetic Wound Healing

Danxia Li,Tao Chen,Yanfang Zhang,Yuanhong Xu,Haitao Niu,

doi : 10.1002/adhm.202100716

Volume 10, Issue 18 2100716

Danxia Li,Tao Chen,Yanfang Zhang,Yuanhong Xu,Haitao Niu,

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