ALBERT

Description: 〈p〉Publication date: Available online 27 January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Simona Baroni, Maria Rosaria Ruggiero, Valeria Bitonto, Lionel M. Broche, David J. Lurie, Silvio Aime, Simonetta Geninatti Crich〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Tumour-associated macrophages (TAM) are forced by cancer cells to adopt an anti-inflammatory phenotype and secrete factors to promote tumour invasion thus being responsible for poor patient outcome. The aim of this study is to develop a clinically applicable, non-invasive method to obtain a quantitative TAM detection in tumour tissue. The method is based on longitudinal proton relaxation rate (R〈sub〉1〈/sub〉) measurements at low field (0.01–1 MHz) to assess the localization of ferumoxytol (clinical approved iron oxide particles) in TAM present in melanoma tumours, where R〈sub〉1〈/sub〉 = 1/T〈sub〉1〈/sub〉. R〈sub〉1〈/sub〉 at low magnetic fields appears highly dependent on the intra or extra cellular localization of the nanoparticles thus allowing an unambiguous TAM quantification. R〈sub〉1〈/sub〉 profiles were acquired on a Fast Field-Cycling relaxometer equipped with a 40 mm wide bore magnet and an 11 mm solenoid detection coil placed around the anatomical region of interest. The R〈sub〉1〈/sub〉 values measured 3 h and 24 h after the injection were significantly different. At 24 h R〈sub〉1〈/sub〉 exhibited a behavior similar to “in vitro” ferumoxytol-labelled J774A.1 macrophages whereas at 3 h, when the ferumoxytol distribution was extracellular, R〈sub〉1〈/sub〉 exhibited higher values similar to that of free ferumoxytol in solution. This finding clearly indicated the intracellular localization of ferumoxytol at 24 h, as confirmed by histological analysis (Pearls and CD68 assays). This information could be hardly achievable from measurements at a single magnetic field and opens new horizons for cell tracking applications using FFC-MRI.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S014296122030051X-fx1.jpg" width="306" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 27 January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Linjie Wang, Yannan Zhao, Feng Yang, Meng Feng, Yazhen Zhao, Xi Chen, Junwei Mi, Yuanjiang Yao, Dongwei Guan, Zhifeng Xiao, Bing Chen, Jianwu Dai〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In situ restoration of severely damaged lung remains difficult due to its limited regeneration capacity after injury. Artificial lung scaffolds are emerging as potential substitutes, but it is still a challenge to reconstruct lung regeneration microenvironment in scaffold after lung resection injury. Here, a 3D biomimetic porous collagen scaffold with similar structure characteristics as lung is fabricated, and a novel collagen binding hepatocyte growth factor (CBD-HGF) is tethered on the collagen scaffold for maintaining the biomimetic function of HGF to improve the lung regeneration microenvironment. The biomimetic scaffold was implanted into the operative region of a rat partial lung resection model. The results revealed that vascular endothelial cells and endogenous alveolar stem cells entered the scaffold at the early stage of regeneration. At the later stage, inflammation and fibrosis were attenuated, the microvascular and functional alveolar-like structures were formed, and the general morphology of the injured lung was restored. Taken together, the functional 3D biomimetic collagen scaffold facilitates recovery of the injured lung, alveolar regeneration, and angiogenesis after acute lung injury. Particularly, this is the first study of lung regeneration in vivo guided by biomimetic collagen scaffold materials, which supports the concept that tissue engineering is an effective strategy for alveolar regeneration.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 27 January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Dianjun Qi, Wen Shi, Adrian R. Black, Mitchell A. Kuss, Xining Pang, Yini He, Bing Liu, Bin Duan〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The small intestine (SI) is difficult to regenerate or reconstruct due to its complex structure and functions. Recent developments in stem cells research, advanced engineering technologies, and regenerative medicine strategies bring new hope of solving clinical problems of the SI. This review will fist summarize the structure, function, development, cell types and matrix components, of the SI. Then, the major cell sources for SI regeneration are introduced, and state-of-the-art biofabrication technologies for generating engineered SI tissues or models are overviewed. Furthermore, 〈em〉in vitro〈/em〉 models and 〈em〉in vivo〈/em〉 transplantation, based on intestinal organoids and tissue engineering, are highlighted. Finally, current challenges and future perspectives are discussed to help direct future applications for SI repair and regeneration.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 27 January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Jianming Chen, Taojian Fan, Zhongjian Xie, Qiqiao Zeng, Ping Xue, Tingting Zheng, Yun Chen, Xiaoling Luo, Han Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Photodynamic therapy (PDT), as a non-invasive therapeutic modality that is alternative to radiotherapy and chemotherapy, is extensively investigated for cancer treatments. Although conventional organic photosensitizers (PSs) are still widely used and have achieved great progresses in PDT, the disadvantages such as hydrophobicity, poor stability within PDT environment and low cell/tissue specificity largely limit their clinical applications. Consequently, nano-agents with promising physicochemical and optical properties have emerged as an attractive alternative to overcome these drawbacks of traditional PSs. Herein, the up-to-date advances in the fabrication and fascinating applications of various nanomaterials in PDT have been summarized, including various types of nanoparticles, carbon-based nanomaterials, and two-dimensional nanomaterials, etc. In addition, the current challenges for the clinical use of PDT, and the corresponding strategies to address these issues, as well as future perspectives on further improvement of PDT have also been discussed.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 235〈/p〉 〈p〉Author(s): Xiaolei Nie, Yon Jin Chuah, Wenzhen Zhu, Pengfei He, Yvonne Peck, Dong-An Wang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Articular cartilage repair has been a long-standing challenge in orthopaedic medicine due to the limited self-regenerative capability of cartilage tissue. Currently, cartilage lesions are often treated by microfracture or autologous chondrocyte implantation (ACI). However, these treatments are frequently reported to result in a mixture of the desired hyaline cartilage and mechanically inferior fibrocartilage. In this study, by combining the advantages of cartilage tissue engineering and decellularization technology, we developed a decellularized allogeneic hyaline cartilage graft, named dLhCG, which achieved superior efficacy in articular cartilage repair and surpassed living autologous chondrocyte-based cartilaginous engraftment and ACI. By the 6-month time point after implantation in porcine knee joints, the fine morphology, composition, phenotype, microstructure and mechanical properties of the regenerated hyaline-like cartilaginous neo-tissue have been demonstrated via histology, biochemical assays, DNA microarrays and mechanical tests. The articular cartilaginous engraftment with allogeneic dLhCG was indicated to be well consistent, compatible and integrated with the native cartilage of the host. The successful repair of articular chondral defects in large animal models suggests the readiness of allogeneic dLhCG for clinical trials.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 235〈/p〉 〈p〉Author(s): Hiroyasu Takemoto, Takanori Inaba, Takahiro Nomoto, Makoto Matsui, Xiaomeng Liu, Masahiro Toyoda, Yuto Honda, Kaori Taniwaki, Naoki Yamada, Junhyun Kim, Keishiro Tomoda, Nobuhiro Nishiyama〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Gemcitabine (GEM) is a powerful anticancer drug for various cancers. However, the anticancer efficacy and the side effects should be addressed for effective therapeutics. To this end, we created a GEM-conjugated polymer (P-GEM) based on cyclic acetal linkage as a delivery carrier of GEM. The obtained P-GEM stably conjugated GEM at physiological pH (i.e., bloodstream), but released GEM in response to acidic environments such as endosome/lysosome. After systemic administration of P-GEM for mice bearing subcutaneous tumors, it achieved prolonged blood circulation and enhanced tumor accumulation relative to free GEM system. In addition, the polymer-drug conjugate structure of P-GEM realized effective distribution in the tumor tissues toward the induction of apoptosis in most areas of the tumor sites. Of note, the molecular design of P-GEM achieved minimal accumulation in normal tissues, resulting in negligible GEM-derived adverse effects (e.g., gastrointestinal toxicity and hematotoxicity). Ultimately, even four times smaller dose of P-GEM on a GEM basis realized comparable/higher tumor growth suppression effect for two distinct pancreatic tumor models, compared to free GEM system. The obtained results suggest the huge potential of the present design of GEM-conjugated polymer for anticancer therapeutics.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 234〈/p〉 〈p〉Author(s): 〈/p〉

Description: 〈p〉Publication date: Available online 27 January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Mohamed Elbadawy, Megumi Yamanaka, Yuta Goto, Kimika Hayashi, Ryouichi Tsunedomi, Shoichi Hazama, Hiroaki Nagano, Toshinori Yoshida, Makoto Shibutani, Ryo Ichikawa, Junta Nakahara, Tsutomu Omatsu, Tetsuya Mizutani, Yukie Katayama, Yuta Shinohara, Amira Abugomaa, Masahiro Kaneda, Hideyuki Yamawaki, Tatsuya Usui, Kazuaki Sasaki〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Non-alcoholic steatohepatitis (NASH) is associated with liver fibrosis and cirrhosis, which eventually leads to hepatocellular carcinoma. Although several animal models were developed to understand the mechanisms of NASH pathogenesis and progression, it remains obscure. A 3D organoid culture system can recapitulate organ structures and maintain gene expression profiles of original tissues. We therefore tried to generate liver organoids from different degrees [defined as mild (NASH A), moderate (NASH B) and severe (NASH C)] of methionine- and choline-deficient diet-induced NASH model mice and analyzed the difference of their architecture, cell components, organoid-forming efficacy, and gene expression profiles. Organoids from each stage of NASH model mice were successfully generated. Interestingly, epithelial-mesenchymal transition was observed in NASH C organoids. Expression of Collagen I and an activated hepatic satellite cell marker, α-sma was upregulated in the liver organoids from NASH B and C mice. The analysis of RNA sequencing revealed that several novel genes were upregulated in all NASH liver organoids. These results suggest that our generated liver organoids from different stages of NASH diseased mice might become a useful tool for in vitro studies of the molecular mechanism of NASH development and also for identifying novel biomarkers for early diagnosis of NASH disease.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 25 January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Ning Ran, Xianjun Gao, Xue Dong, Junjin Li, Caorui Lin, Mengyuan Geng, HaiFang Yin〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Duchenne muscular dystrophy (DMD) is a devastating disorder caused by loss of functional dystrophin protein, resulting in muscle wasting. Enhancing muscle growth by inhibiting myostatin, a growth factor negatively regulating skeletal muscle mass, is a promising approach to slow disease progression. Direct administration of myostatin propeptide, a natural inhibitor of mature myostatin, has shown limited efficacy probably due to low serum stability. Here, we demonstrate that serum stability, delivery efficiency and efficacy of propeptide can be significantly enhanced by anchoring propeptide to the surface of exosomes by fusing the inhibitory domain of myostatin propeptide into the second extracellular loop of CD63 (EXOpro). Repeated administrations of EXOpro accelerated muscle regeneration and growth, resulting in significantly increased muscle mass and functional rescue without any detectable toxicity in 〈em〉mdx〈/em〉 mice. Importantly, EXOpro partially rehabilitated bone structure and promoted bone regeneration in 〈em〉mdx〈/em〉 mice. Our findings demonstrate that anchoring to exosomes increased delivery and serum stability of propeptide and augmented the inhibitory efficacy of myostatin propeptide and thus provide a delivery platform for propeptide-based intervention in DMD.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 24 January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Hui Zhou, Youcong Gong, Yanan Liu, Anlian Huang, Xufeng Zhu, Jiawei Liu, Guanglong Yuan, Li Zhang, Ji-an Wei, Jie Liu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Alzheimer's disease (AD) seriously affects human health and life and lacks effective treatments. The lessons of many clinical trial failures suggest that targeting amyloid beta to treat AD is difficult, and finding new targets is an important direction for AD drug research. The neurofibrillary tangles formed by hyperphosphorylation of tau protein induce the production of cytotoxic reactive oxygen species (ROS) and cause neuronal apoptosis. Therefore, inhibition of hyperphosphorylation of tau protein and reduction of neuronal damage have become promising methods for the treatment of AD. We herein designed a novel nanocomposite with high stability and good biocompatibility by using flower-shaped hollow nano-ruthenium (Ru NPs) as a carrier, loading nerve growth factor (NGF) and sealing with phase change material (PCM). Due to its excellent photothermal effect, under the near-infrared (NIR) irradiation, the nanocomposite could effectively penetrate the blood-brain barrier (BBB) and respond to phase changes in the lesion area, releasing NGF, which inhibited tau hyperphosphorylation, reduced oxidative stress, and more importantly restored nerve damage and maintained neuronal morphology, thereby significantly improving learning and memory in AD mice. Thus, the experimental results indicate that multifunctional nanocomposites may be a promising drug in the treatment of AD.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 235〈/p〉 〈p〉Author(s): Han Wang, Zhaohui Wang, Yuanbiao Tu, Yongkuan Li, Tian Xu, Man Yang, Peng Wang, Yueqing Gu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Cancer starvation therapy based on catalytic chemistry of glucose oxidase (GOx) offers great potential for multimodal treatment, benefiting from both nutrition shutting-off and the oxidization product hydrogen peroxide (H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉). Herein, further optimization of such combined therapy was achieved by a cascade Nano-reactor, which was constructed by incorporating GOx into a bio-mimic upconversion nanosystem. The cascade began when GOx was delivered into tumor sites through homotypic targeting, facilitating selective starving of cancer cells and H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 generation. Then, upon 980 nm laser excitation, the 470 nm light emitted by upconversion nanoparticles (NaYF〈sub〉4〈/sub〉: Yb, Tm) photolyzed H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 into hydroxyl radical for phototherapy, superior to direct photolysis by blue light with limited tissue penetration depth. Meanwhile, the 800 nm emission of UCNPs was used to track the 〈em〉in vivo〈/em〉 fate and tumor targeting ability of the Nano-reactor. Radionuclide imaging further confirmed the targeting of the Nano-reactor to subcutaneous 4T1 tumor and lung metastasis. Significantly enhanced therapeutic efficacy of this cascade starvation-phototherapy was validated 〈em〉in vitro〈/em〉 and 〈em〉in vivo〈/em〉, suggesting the Nano-reactor as a smart, simple and strong system for cancer multimodal therapy.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 235〈/p〉 〈p〉Author(s): Huan Xu, Mengying Hu, Mengrui Liu, Sai An, Kaiyun Guan, Menglin Wang, Lei Li, Jing Zhang, Jun Li, Leaf Huang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Tumor associated fibroblasts (TAFs) are key stromal cells mediating the desmoplastic reaction and being partially responsible for the drug-resistance and immunosuppressive microenvironment formation in solid tumors. Delivery of genotoxic drugs off-targetedly to kill TAFs results in production of Wnt16 which renders the neighboring tumor cells drug resistant as shown in our previous study (PMC4623876). Our current approach looks for means to deactivate, rather than kill, TAFs. Reactive oxygen species (ROS) are the central hub of multiple profibrogenic pathways and indispensable for TAFs activation. Herein, puerarin was identified to effectively downregulate ROS production in the activated myofibroblast. In this study, a novel puerarin nanoemulsion (nanoPue) was developed to improve the solubility and bioavailability of puerarin. NanoPue significantly deactivated the stromal microenvironment (e.g., ~6-fold reduction of TAFs in nanoPue treated mice compared with the PBS control, p 〈 0.0001) and facilitated chemotherapy effect of nano-paclitaxel in the desmoplastic triple-negative breast cancer (TNBC) model. Moreover, the removal of the physical barrier increased intra-tumoral infiltration of cytotoxic T cell by 2-fold. This activated immune microenvironment allowed nanoPue to synergize PD-L1 blockade therapy in TNBC model.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 17 January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Marietta Landgraf, Christoph A. Lahr, Ishdeep Kaur, Abbas Shafiee, Alvaro Sanchez-Herrero, Phillip W. Janowicz, Akhilandeshwari Ravichandran, Christopher B. Howard, Anna Cifuentes-Rius, Jacqui A. McGovern, Nicolas H. Voelcker, Dietmar W. Hutmacher〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈p〉In advanced breast cancer (BCa) patients, not the primary tumor, but the development of distant metastases, which occur mainly in the organ bone, and their adverse health effects are responsible for high mortality. Targeted delivery of already known drugs which displayed potency, but rather unfavorable pharmacokinetic properties, might be a promising approach to overcome the current limitations of metastatic BCa therapy.〈/p〉 〈p〉Camptothecin (CPT) is a highly cytotoxic chemotherapeutic compound, yet poorly water-soluble and non-specific. Here, CPT was loaded into porous silicon nanoparticles (pSiNP) displaying the epidermal growth factor receptor (EGFR)-targeting antibody (Ab) cetuximab to generate a soluble and targeted nanoscale delivery vehicle for cancer treatment.〈/p〉 〈p〉After confirming the cytotoxic effect of targeted CPT-loaded pSiNP 〈em〉in vitro〈/em〉 on MDA-MB-231BO cells, nanoparticles were studied in a humanized BCa bone metastasis mouse model. Humanized tissue-engineered bone constructs (hTEBCs) provided a humanized microenvironment for BCa bone metastases in female NOD-scid IL2Rg〈sup〉null〈/sup〉 (NSG) mice. Actively targeted CPT-loaded pSiNP led to a reduction of orthotopic primary tumor growth, increased survival rate and significant decrease in hTEBC and murine lung, liver and bone metastases. This study demonstrates that targeted delivery via pSiNP is an effective approach to employ CPT and other potent anti-cancer compounds with poor pharmacokinetic profiles in cancer therapy.〈/p〉 〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0142961220300375-fx1.jpg" width="485" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 235〈/p〉 〈p〉Author(s): Xiaohua Zheng, Lei Wang, Yuyao Guan, Qing Pei, Jian Jiang, Zhigang Xie〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Porphyrin-based porous organic polymers are highly potential candidates for cancer theranostics. However, un-controllable particle size and unclear photoactive mechanisms have been deemed to be “Achilles’ heels” for their biomedical application. Herein, a facile self-template strategy has been applied to integrate two types of porous materials to build the MOF@POP-PEG nanocomposite (named HUC-PEG). As-synthesized HUC-PEG exhibited controllable particle shape and size, good biocompatibility, and better colloidal stability. Importantly, synergy “0 + 1 〉 1” interface effects have been demonstrated to simultaneously enhance both the generation of more singlet oxygen (〈sup〉1〈/sup〉O〈sub〉2〈/sub〉) for photodynamic therapy (PDT) and local hyperthermia for photothermal therapy (PTT), thus to achieve favorable proliferation inhibition of tumor cell both in vitro and in vivo. Moreover, the strong X-ray attenuating ability of Hf element and excellent photothermal conversion efficacy endow this nanocomposite with computed tomography (CT)/photothermal imaging functions. We believe that our ingenious design may open a new horizon for the preparation of nanoscale POP-based therapeutic agents and also realize a paradigm shift in the understanding of photoactive mechanism in porous materials.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 235〈/p〉 〈p〉Author(s): Zheyu Shen, Ting Liu, Zhen Yang, Zijian Zhou, Wei Tang, Wenpei Fan, Yijing Liu, Jing Mu, Ling Li, Vladimir I. Bregadze, Swadhin K. Mandal, Anna A. Druzina, Zhenni Wei, Xiaozhong Qiu, Aiguo Wu, Xiaoyuan Chen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Glioblastoma (GBM) is one of the most malignant tumors with poor prognosis and outcomes. Although smaller particle size can lead to higher blood-brain barrier (BBB)-permeability of the nanomaterials, most of the reported BBB-crossable nanomaterials for targeted GBM therapy are larger than 24 nm. To realize theranostics of GBM, co-loading of therapeutic and diagnostic agents on the same nanomaterials further results in larger particle size. In this study, we developed a kind of novel BBB-transportable nanomaterials smaller than 14 nm for high-efficiency theranostics of GBM (〈em〉i.e.〈/em〉, high contrast magnetic resonance imaging (MRI) and radiosensitization of GBM). Typically, poly(acrylic acid) (PAA) stabilized extremely small gadolinium oxide nanoparticles with modification of reductive bovine serum albumin (ES-GON-rBSA) was synthesized in water phase, resulting in excellent water-dispersibility. RGD dimer (RGD2, Glu-{Cyclo[Arg-Gly-Asp-(D-Phe)-Lys]}〈sub〉2〈/sub〉) and lactoferrin (LF) were then conjugated to the ES-GON-rBSA to obtain composite nanoparticle ES-GON-rBSA-LF-RGD2 with extraordinary relaxivities (〈em〉r〈/em〉〈sub〉1〈/sub〉 = 60.8 mM〈sup〉−1〈/sup〉 s〈sup〉−1〈/sup〉, 〈em〉r〈/em〉〈sub〉2〈/sub〉/〈em〉r〈/em〉〈sub〉1〈/sub〉 = 1.1). The maximum signal enhancement (ΔSNR) for 〈em〉T〈/em〉〈sub〉1〈/sub〉-weighted MRI of tumors reached up to 423 ± 42% at 12 h post-injection of ES-GON-rBSA-LF-RGD2, which is much higher than commercial Gd-chelates (〈80%). ES-GON-rBSA-LF-RGD2 exhibited high biocompatibility and can transport across the 〈em〉in vitro〈/em〉 BBB model and the 〈em〉in vivo〈/em〉 BBB of mice due to its small particle size (〈em〉d〈/em〉〈sub〉〈em〉h〈/em〉〈/sub〉 = 13.4 nm) and LF receptor mediated transcytosis. Orthotopic GBM studies reinforce that ES-GON-rBSA3-LF-RGD2 can accumulate in the orthotopic GBM and enhance the radiation therapy of GBM as an effective radiosensitizing agent.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 21 January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Heyong Yin, Franziska Strunz, Zexing Yan, Jiaju Lu, Christoph Brochhausen, Stefanie Kiderlen, Hauke Clausen-Schaumann, Xiumei Wang, Manuela E. Gomes, Volker Alt, Denitsa Docheva〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The poor healing capacity of tendons is known to worsen in the elderly. During tendon aging and degeneration, endogenous human tendon stem/progenitor cells (hTSPCs) experience profound pathological changes. Here, we explored a rejuvenation strategy for hTSPCs derived from aged/degenerated Achilles tendons (A-TSPCs) by a providing three-dimensional (3D) nanofiber hydrogels and comparing them to young/healthy TSPCs (Y-TSPCs). RADA peptide hydrogel has a self-assembling ability, forms a nanofibrous 3D niche and can be further functionalized by adding RGD motifs. Cell survival, apoptosis, and proliferation assays demonstrated that RADA and RADA/RGD hydrogels support A-TSPCs in a comparable manner to Y-TSPCs. Moreover, they rejuvenated A-TSPCs to a phenotype similar to that of Y-TSPCs, as evidenced by restored cell morphology and cytoskeletal architecture. Transmission electron, confocal laser scanning and atomic force microscopies demonstrated comparable ultrastructure, surface roughness and elastic modulus of A- and Y-TSPC-loaded hydrogels. Lastly, quantitative PCR revealed similar expression profiles as well a significant upregulation of genes related to tenogenesis and multipotency. Taken together, the RADA-based hydrogels exert a rejuvenating effect by recapitulating 〈em〉in vitro〈/em〉 specific features of the natural microenvironment of human TSPCs, which strongly indicates their potential to direct cell behaviour and overcome the challenge of cell aging and degeneration in tendon repair.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 235〈/p〉 〈p〉Author(s): Jiefei Wang, Zhongjie Wang, Yong Zhong, Yan Zou, Chong Wang, Haigang Wu, Albert Lee, Weitao Yang, Xiao Wang, Yanjie Liu, Dongya Zhang, Jiliang Yan, Mingcong Hao, Meng Zheng, Roger Chung, Feng Bai, Bingyang Shi〈/p〉

Description: 〈p〉Publication date: Available online 20 January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Lijuan Wen, Kai Wang, Fengtian Zhang, Yanan Tan, Xuwei Shang, Yun Zhu, Xueqing Zhou, Hong Yuan, Fuqiang Hu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Glioblastoma (GBM) is one of the malignant tumors with high mortality, and the presence of the blood brain barrier (BBB) severely limits the penetration and tissue accumulation of therapeutic agents in the lesion of GBM. Active targeting nanotechnologies can achieve efficient drug delivery in the brain, while still have a very low success rate. Here we revealed a previously unexplored phenomenon that chemotherapy with active targeting nanotechnologies causes pathological BBB functional recovery through VEGF-PI3K-AKT signaling pathway inhibition, accompanied with up-regulated expression of Claudin-5 and Occludin. Seriously, pathological BBB functional recovery induces a significant decrease of intracerebral active targeting nanotechnologies transport during GBM multiple administration, leading to chemotherapy failure in GBM therapeutics. To address this issue, we chose AKT agonist SC79 to transiently re-open functional recovering pathological BBB for continuously intracerebral delivery of brain targeted nanotherapeutics, finally producing an observable anti-GBM effect 〈em〉in vivo〈/em〉, which may offer new sight for other CNS disease treatment.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 16 January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Songlei Zhou, Yukun Huang, Yu Chen, Shanshan Liu, Minjun Xu, Tianze Jiang, Qingxiang Song, Gan Jiang, Xiao Gu, Xiaoling Gao, Jun Chen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Efficient delivery of vaccines to dendritic cells (DCs) is critical for inducing sufficient immune response and realizing effective cancer immunotherapy. In the past decade, researchers have spent tremendous effort in delivering vaccines by using nanoparticles. However, most of the present strategies are designed based on receptor-mediated endocytosis to increase nanovaccines uptake by DCs, and underestimate the role of macropinocytosis in taking up exogenous antigen. Here, we proposed that macropinocytosis, an efficient pathway for DCs to internalize extracellular fluid-phase solutes, might be utilized as a highly-effective approach to facilitate nanovaccines uptake in DCs. Accordingly, we designed a biomimetic nanovaccine (R837-αOVA-ApoE3-HNP), composing of a poly-(D, 〈span〉l〈/span〉-lactide-co-glycolide) (PLGA) core to encapsulate adjuvant imiquimod (R837), a phospholipid membrane to load antigen peptide (αOVA), and apolipoprotein E3 (ApoE3), to boost the internalization of antigens into DCs. The nanovaccine exhibited highly efficient cellular uptake into DCs through the macropinocytosis pathway, and significantly promoted DCs maturation and antigen presentation. After subcutaneous injection, the nanovaccine was efficiently drained to lymph nodes. Strong T cell immune responses including the generation of antigen-specific CD8〈sup〉+〈/sup〉 T cells, expansion of IFN-γ〈sup〉+〈/sup〉 CD8〈sup〉+〈/sup〉 T cells and the secretion of IFN-γ〈sup〉+〈/sup〉 were observed after the vaccination of R837-αOVA-ApoE3-HNP. It also efficiently inhibited the formation of tumor metastasis in lung as a prevention vaccine, and exerted superior therapeutic efficiency on B16-OVA tumor-bearing mice when in combination with αPD-1 therapy. Overall, our work demonstrated that by utilizing the macropinocytosis pathway, ApoE3-incorporated biomimetic nanoparticle has great potential to function as a feasible, effective, and safe nanovaccine for cancer immunotherapy.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0142961220300417-fx1.jpg" width="325" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 235〈/p〉 〈p〉Author(s): Helin Xing, Xing Wang, Gao Xiao, Zongmin Zhao, Shiquan Zou, Man Li, Joseph J. Richardson, Blaise L. Tardy, Liangxia Xie, Satoshi Komasa, Joji Okazaki, Qingsong Jiang, Guodong Yang, Junling Guo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Advancing bone implant engineering offers the opportunity to overcome crucial medical challenges and improve clinical outcomes. Although the establishment of a functional vascular network is crucial for bone development, its regeneration inside bone tissue has only received limited attention to date. Herein, we utilize siRNA-decorated particles to engineer a hierarchical nanostructured coating on clinically used titanium implants for the synergistic regeneration of skeletal and vascular tissues. Specifically, an siRNA was designed to target the regulation of cathepsin K and conjugated on nanoparticles. The functionalized nanoparticles were assembled onto the bone implant to form a hierarchical nanostructured coating. By regulating mRNA transcription, the coating significantly promotes cell viability and growth factor release related to vascularization. Moreover, microchip-based experiments demonstrate that the nanostructured coating facilitates macrophage-induced synergy in up-regulation of at least seven bone and vascular growth factors. Ovariectomized rat and comprehensive beagle dog models highlight that this siRNA-integrated nanostructured coating possesses all the key traits of a clinically promising candidate to address the myriad of challenges associated with bone regeneration.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉siRNA-decorated nanoparticles were assembled to engineer a hierarchical nanostructured coating on clinically used titanium implants for the synergistic regeneration of skeletal and vascular tissues. The release of siRNA targeted the regulation of cathepsin K and enhanced bone-implant interfacial interaction. siRNA-〈em〉CTSK〈/em〉 could be released and internalized by the adjacent macrophages, demonstrating a therapeutic improvement on the osteointegration with synergetic effects on bone regeneration and blood vessel system repair in vitro and 〈em〉in vivo〈/em〉. The use of multi-scaled bio-functional coatings as presented herein may find applications in regenerative medicine for other tissue due to their ability to favor complex stem cell differentiation paths.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0142961220300302-fx1.jpg" width="500" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 13 January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Zejun Wang, Hongjun Li, Jinqiang Wang, Zhaowei Chen, Guojun Chen, Di Wen, Amanda Chan, Zhen Gu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The integration of sampling and instant metabolite readout can fundamentally elevate patient compliance. To circumvent the need for complex in-lab apparatus, here, an all-in-one sampling and display transdermal colorimetric microneedle patch was developed for sensing hyperglycemia in mice. The coloration of 3,3′,5,5′-tetramethylbenzidine (TMB) is triggered by the cascade enzymatic reactions of glucose oxidase (GOx) and horseradish peroxidase (HRP) at abnormally high glucose levels. The HRP in the upper layer is biomineralized with calcium phosphate (CaP) shell to add a pH responsive feature for increased sensitivity as well as protection from nonspecific reactions. This colorimetric sensor achieved minimally invasive extraction of the interstitial fluid from mice and converted glucose level to a visible color change promptly. Quantitative red green and blue (RGB) information could be obtained through a scanned image of the microneedle. This costless, portable colorimetric sensor could potentially detect daily glucose levels without blood drawing procedures.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 233〈/p〉 〈p〉Author(s): Zhenzhen Wang, Kai Dong, Zhen Liu, Yan Zhang, Zhaowei Chen, Hanjun Sun, Jinsong Ren, Xiaogang Qu〈/p〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 234〈/p〉 〈p〉Author(s): Junjie Ren, Lei Zhang, Jiayi Zhang, Wei Zhang, Yang Cao, Zhigang Xu, Hongjuan Cui, Yuejun Kang, Peng Xue〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Glucose oxidase (GOx)-mediated starvation circumvents the energy supply for tumor growth, which has been proved as a potent tumor treatment modality. However, tumor hypoxia negatively affects the efficacy of oxygen-involved glucose decomposition reaction. Moreover, curative effect via glucose depletion is not usually satisfactory enough and adjuvant remedies are always required for a promoted tumor ablation. Herein, a multifunctional nanoreactor based on hollow Bi〈sub〉2〈/sub〉Se〈sub〉3〈/sub〉 nanoparticles was developed by loading oxygenated perfluorocarbon (PFC) and surface modification with GOx, which was exploited for an enhanced tumor starvation and highly sensitive photothermal therapy (PTT). GOx-mediated tumor starvation could impede the adenosine triphosphate (ATP) generation and further downregulate the expression of heat shock protein (HSP) to decrease the thermoresistance of cells. Afterwards, near infrared (NIR) laser irradiation was performed not only to trigger sensitized PTT but also to initiate the release of encapsulated oxygen to relieve local hypoxia. Then, such GOx-mediated tumor starvation would be further amplified, accompanying with secondary enhanced suppression of HSP. Both 〈em〉in vitro〈/em〉 and 〈em〉in vivo〈/em〉 investigations demonstrated that such nanoreactor can realize a fascinating therapeutic outcome with minimal adverse effects in virtue of the improved synergistic starvation therapy and PTT. Taken together, the proposed treatment paradigm may inspire the future development of more intelligent nanoplatforms toward high efficient cancer therapy.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 234〈/p〉 〈p〉Author(s): Shi-Bo Wang, Zhao-Xia Chen, Fan Gao, Cheng Zhang, Mei-Zhen Zou, Jing-Jie Ye, Xuan Zeng, Xian-Zheng Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Photodynamic therapy (PDT) is a promising treatment modality for tumor suppression. However, the hypoxic state of most solid tumors might largely hinder the efficacy of PDT. Here, a functional covalent organic framework (COF) is fabricated to enhance PDT efficacy by remodeling the tumor extracellular matrix (ECM). Anti-fibrotic drug pirfenidone (PFD) is loaded in an imine-based COF (COF〈sub〉TTA-DHTA〈/sub〉) and followed by the decoration of poly(lactic-co-glycolic-acid)-poly(ethylene glycol) (PLGA-PEG) to fabricate PFD@COF〈sub〉TTA-DHTA〈/sub〉@PLGA-PEG, or PCPP. After injected intravenously, PCPP can accumulate and release PFD in tumor sites, leading to down-regulation of ECM compenents such as hyaluronic acid (HA) and collagen I. Such depletion of tumor ECM reduces the intratumoral solid stress, a compressive force exerted by the ECM and cells, decompresses tumor blood vessels, and increases the density of effective vascular areas, resulting in significantly improved oxygen supply in tumor. Furthermore, PCPP-mediated tumor ECM depletion also enhances the tumor uptake of subsequently injected Protoporphyrinl IX (PPIX)-conjugated peptide formed nanomicelles (NM-PPIX) due to the improved enhanced permeability and retention (EPR) effect. Both the alleviated tumor hypoxia and improved tumor homing of photosensitizer (PS) molecules after PCPP treatment significantly increase the reactive oxygen species (ROS) generation in tumor and therefore realize greatly enhanced PDT effect of tumor in vivo.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉A covalent organic framework (COF)-based nanosystem PCPP was fabricated to enhance tumor photodynamic therapy (PDT). PCPP can trigger the depletion of tumor extracellular matrix (ECM), leading to improved oxygen supply as well as photosensitizer uptake in tumor to achieve enhanced tumor PDT.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0142961220300181-fx1.jpg" width="276" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 233〈/p〉 〈p〉Author(s): Zhengwei Liu, Faming Wang, Jinsong Ren, Xiaogang Qu〈/p〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 234〈/p〉 〈p〉Author(s): Seep Arora, Shiming Lin, Christine Cheung, Evelyn K.F. Yim, Yi-Chin Toh〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The effective deployment of arterial (AECs), venous (VECs) and stem cell-derived endothelial cells (PSC-ECs) in clinical applications requires understanding of their distinctive phenotypic and functional characteristics, including their responses to microenvironmental cues. Efforts to mimic the 〈em〉in-vivo〈/em〉 vascular basement membrane milieu have led to the design and fabrication of nano- and micro-topographical substrates. Although the basement membrane architectures of arteries and veins are different, investigations into the effects of substrate topographies have so far focused on generic EC characteristics. Thus, topographical modulation of arterial- or venous-specific EC phenotype and function remains unknown. Here, we comprehensively evaluated the effects of 16 unique topographies on primary AECs, VECs and human PSC-ECs using a Multi Architectural (MARC) Chip. Gratings and micro-lenses augmented venous-specific phenotypes and depressed arterial functions in VECs; while AECs did not respond consistently to topography. PSC-ECs exhibited phenotypic and functional maturation towards an arterial subtype with increased angiogenic potential, NOTCH1 and Ac-LDL expression on gratings. Specific topographies could elicit different phenotypic and functional changes, despite similar morphological response in different ECs, demonstrating no direct correlation between the two responses.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 233〈/p〉 〈p〉Author(s): Chao Shi, Mingle Li, Zhen Zhang, Qichao Yao, Kun Shao, Feng Xu, Ning Xu, Haidong Li, Jiangli Fan, Wen Sun, Jianjun Du, Saran Long, Jingyun Wang, Xiaojun Peng〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Photodynamic therapy (PDT) and chemotherapy has been applied as a prospective approach in tumor therapeutics. However, suffering from the inherent hypoxia status in tumor microenvironment (TME), the anticancer efficiency is enormously restricted, especially PDT. Herein, we develop a unique liposomal encapsulated catalase (CAT), lyso-targeted NIR photosensitizer (MBDP) and doxorubicin (Dox), forming FA-L@MD@CAT, to increase tumor oxygenation by catalyzing intratumoral high-expressed H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 for enhancing the combination of chemo-PDT. Moreover, the enhanced tumoral oxygenation not only facilitates singlet oxygen (〈sup〉1〈/sup〉O〈sub〉2〈/sub〉) production but also reverses immunosuppressive TME by modulating immune cytokines to favor antitumor immunities, which significantly induce tumor death. Notably, this system also realizes specific tumor recognition to folate receptor upregulated tumors and improves intratumoral accumulation. This work provides an effective strategy to promote tumor therapeutic index, which may possess a promising future in clinical application.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 234〈/p〉 〈p〉Author(s): Nayana Tusamda Wakhloo, Sebastian Anders, Florent Badique, Melanie Eichhorn, Isabelle Brigaud, Tatiana Petithory, Maxime Vassaux, Jean-Louis Milan, Jean-Noël Freund, Jürgen Rühe, Patricia M. Davidson, Laurent Pieuchot, Karine Anselme〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Cell deformation occurs in many critical biological processes, including cell extravasation during immune response and cancer metastasis. These cells deform the nucleus, their largest and stiffest organelle, while passing through narrow constrictions 〈em〉in vivo〈/em〉 and the underlying mechanisms still remain elusive. It is unclear which biochemical actors are responsible and whether the nucleus is pushed or pulled (or both) during deformation. Herein we use an easily-tunable poly-L-lactic acid micropillar topography, mimicking 〈em〉in vivo〈/em〉 constrictions to determine the mechanisms responsible for nucleus deformation. Using biochemical tools, we determine that actomyosin contractility, vimentin and nucleo-cytoskeletal connections play essential roles in nuclear deformation, but not A-type lamins. We chemically tune the adhesiveness of the micropillars to show that pulling forces are predominantly responsible for the deformation of the nucleus. We confirm these results using an 〈em〉in silico〈/em〉 cell model and propose a comprehensive mechanism for cellular and nuclear deformation during confinement. These results indicate that microstructured biomaterials are extremely versatile tools to understand how forces are exerted in biological systems and can be useful to dissect and mimic complex 〈em〉in vivo〈/em〉 behaviour.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 26 February 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Su-Hwan Kim, Kyungmin Kim, Beom Seok Kim, Young-Hyeon An, Uk-Jae Lee, Sang-Hyuk Lee, Seunghyun L. Kim, Byung-Gee Kim, Nathaniel S. Hwang〈/p〉

Description: 〈p〉Publication date: Available online 21 February 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Xintao Zhang, Bui Anthony, Zheng Chai, Amanda Lee Dobbins, Roger Bryan Sutton, Chengwen Li〈/p〉

Description: 〈p〉Publication date: Available online 20 February 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Jingxian Feng, Minjun Xu, Jiahao Wang, Songlei Zhou, Yipu Liu, Shanshan Liu, Yukun Huang, Yu Chen, Liang Chen, Qingxiang Song, Jingru Gong, Huiping Lu, Xiaoling Gao, Jun Chen〈/p〉

Description: 〈p〉Publication date: May 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 241〈/p〉 〈p〉Author(s): Liangliang Dai, Xiang Li, Mengjiao Yao, Peiyun Niu, Xichen Yuan, Ke Li, Maowen Chen, Zengxiang Fu, Xianglong Duan, Haibin Liu, Kaiyong Cai, Hui Yang〈/p〉

Description: 〈p〉Publication date: Available online 19 February 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Xiuli Zhang, Feng Chen, Melik Z. Turker, Kai Ma, Pat Zanzonico, Fabio Gallazzi, Manankumar A. Shah, Austin R. Prater, Ulrich Wiesner, Michelle S. Bradbury, Michael R. McDevitt, Thomas P. Quinn〈/p〉

Description: 〈p〉Publication date: May 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 240〈/p〉 〈p〉Author(s): Jingjie Yeo, Yimin Qiu, Gang Seob Jung, Yong-Wei Zhang, Markus J. Buehler, David L. Kaplan〈/p〉

Description: 〈p〉Publication date: May 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 240〈/p〉 〈p〉Author(s): Aline L.Y. Nachlas, Siyi Li, Benjamin W. Streeter, Kenneth J. De Jesus Morales, Fatiesa Sulejmani, David Immanuel Madukauwa-David, Donald Bejleri, Wei Sun, Ajit P. Yoganathan, Michael E. Davis〈/p〉

Description: 〈p〉Publication date: May 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 240〈/p〉 〈p〉Author(s): Yanan Gao, Zhihua Li, Yin Hong, Tingting Li, Xiaoyan Hu, Luyao Sun, Zhengchang Chen, Zijian Chen, Zhiheng Luo, Xin Wang, Jian Kong, Guanglei Li, Hsing-Lin Wang, Hwa Liang Leo, Hanry Yu, Lei Xi, Qiongyu Guo〈/p〉

Description: 〈p〉Publication date: April 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 238〈/p〉 〈p〉Author(s): Sunil Singh, Lucille A. Ray, Pradip Shahi Thakuri, Sydnie Tran, Michael C. Konopka, Gary D. Luker, Hossein Tavana〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Fibroblasts are a critical component of tumor microenvironments and associate with cancer cells physically and biochemically during different stages of the disease. Existing cell culture models to study interactions between fibroblasts and cancer cells lack native tumor architecture or scalability. We developed a scalable organotypic model by robotically encapsulating a triple negative breast cancer (TNBC) cell spheroid within a natural extracellular matrix containing dispersed fibroblasts. We utilized an established CXCL12 – CXCR4 chemokine-receptor signaling in breast tumors to validate our model. Using imaging techniques and molecular analyses, we demonstrated that CXCL12-secreting fibroblasts have elevated activity of RhoA/ROCK/myosin light chain-2 pathway and rapidly and significantly contract collagen matrices. Signaling between TNBC cells and CXCL12-producing fibroblasts promoted matrix invasion of cancer cells by activating oncogenic mitogen-activated protein kinase signaling, whereas normal fibroblasts significantly diminished TNBC cell invasiveness. We demonstrated that disrupting CXCL12 – CXCR4 signaling using a molecular inhibitor significantly inhibited invasiveness of cancer cells, suggesting blocking of tumor-stromal interactions as a therapeutic strategy especially for cancers such as TNBC that lack targeted therapies. Our organotypic tumor model mimics native solid tumors, enables modular addition of different stromal cells and extracellular matrix proteins, and allows high throughput compound screening against tumor-stromal interactions to identify novel therapeutics.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: April 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 238〈/p〉 〈p〉Author(s): Chunfang Wei, Yanan Liu, Xufeng Zhu, Xu Chen, Yanhui Zhou, Guanglong Yuan, Youcong Gong, Jie Liu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The application of nanozymes to specifically treat tumors in the tumor microenvironment (TME) would be a novel and effective strategy. Here, ultra-small IrRu alloy nanoparticles (IrRu NPs) with dual enzyme activities were synthesized by a simple method. PEG surface modification was carried out to improve the biocompatibility of nanoparticles. Meanwhile, the natural enzyme glucose oxidase (GOx) was loaded to synthesize a multi-enzyme nanoreactor (IrRu-GOx@PEG NPs) that could undergo cascade catalytic reaction. In the first catalytic stage, GOx in IrRu-GOx@PEG NPs degraded tumor tissue-sensitive glucose to hydrogen peroxide (H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉), which cut off the nutrient source of the tumor and inhibited tumor growth by starvation therapy. In the second catalytic stage, IrRu NPs in IrRu-GOx@PEG NPs catalyzed the upstream endogenous H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 to highly toxic singlet oxygen 〈sup〉1〈/sup〉O〈sub〉2〈/sub〉 and O〈sub〉2〈/sub〉. Among them, 〈sup〉1〈/sup〉O〈sub〉2〈/sub〉 could directly induce apoptosis of cancer cells by the oxidative therapy, and O〈sub〉2〈/sub〉 could resolve the problem of hypoxia that easily led to the termination of the starvation therapy response in tumor microenvironment, thereby making the cycle of starvation therapy-related reactions continue to occur. It also inhibited the metastasis of tumors caused by hypoxia. In vitro catalytic activity studies showed that IrRu-GOx@PEG NPs had good and stable catalytic activity and could effectively induce apoptosis of 4T1 cancer cells. In addition, in vivo results further demonstrated that IrRu-GOx@PEG NPs could effectively treat breast cancer in combination with starvation therapy and oxidative therapy. This treatment strategy is expected to be used in the treatment of other cancers, bringing new treatment strategies for cancer treatment.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 4 February 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Xiang Xiong, Zeng Xu, Huabei Huang, Yi Wang, Jingya Zhao, Xing Guo, Shaobing Zhou〈/p〉

Description: 〈p〉Publication date: April 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 238〈/p〉 〈p〉Author(s): Yang Bo, Yunjiang Jiang, Kangmei Chen, Kaimin Cai, Wenming Li, Jarron Roy, Yan Bao, Jianjun Cheng〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The early 〈em〉in vivo〈/em〉 diagnosis of infectious disease foci is largely hindered by invasion and concealment of pathogens in host cells, making it difficult for conventional probes to detect and analyze intracellular pathogens. Taking advantage of the excessively produced reactive oxygen species (ROS) within host cells, herein we report the design of thiol-hemiketal blocked N-azidoacetyl galactosamine (Ac〈sub〉3〈/sub〉GalNAzSP), an azido unnatural sugar bearing an unprecedent designed ROS-responsive moiety for targeted labelling of infected host cells. Ac〈sub〉3〈/sub〉GalNAzSP showed great stability under physiological conditions, specifically released active unnatural sugar in host cells overproducing ROS, metabolically labeled infected host cells with azido groups, and enabled targeting 〈em〉in vivo〈/em〉 infection sites by subsequent Click Chemistry reactions, substantiating an unprecedented approach for targeting infected host cells. This technique could be a powerful tool for early 〈em〉in vivo〈/em〉 diagnosis and targeted treatment of infectious disease.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉We report the design of caged N-azidoacetyl galactosamine (Ac〈sub〉3〈/sub〉GalNAzSP), an azido unnatural monosaccharide bearing an unprecedent moiety for targeted metabolic labelling of infected host cells in response to overexpressed ROS. The labelling will enable an efficient targeting approach towards the 〈em〉in vivo〈/em〉 infection site by subsequent Click Chemistry reactions.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0142961220300892-fx1.jpg" width="233" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: April 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 238〈/p〉 〈p〉Author(s): Emeka B. Okeke, Cameron Louttit, Chris Fry, Alireza Hassani Najafabadi, Kai Han, Jean Nemzek, James J. Moon〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Neutrophil elastase (NE) is a serine protease stored in the azurophilic granules of neutrophils and released into the extracellular milieu during inflammatory response or formation of neutrophil extracellular traps (NETs). Neutrophils release NETs to entrap pathogens by externalizing their cellular contents in a DNA framework decorated with anti-microbials and proteases, including NE. Importantly, excess NETs in tissues are implicated in numerous pathologies, including sepsis, rheumatoid arthritis, vasculitis, and cancer. However, it remains unknown how to effectively prevent NET formation. Here, we show that NE plays a major role during NET formation and that inhibition of NE is a promising approach for decreasing NET-mediated tissue injury. NE promoted NET formation by human neutrophils. Whereas sivelestat, a small molecule inhibitor of NE, inhibited the formation of NETs 〈em〉in vitro〈/em〉 , administration of free sivelestat did not have any efficacy in a murine model of lipopolysaccharide-induced endotoxic shock. To improve the efficacy of sivelestat 〈em〉in vivo〈/em〉, we have developed a nanoparticle system for delivering sivelestat. We demonstrate that nanoparticle-mediated delivery of sivelestat effectively inhibited NET formation, decreased the clinical signs of lung injury, reduced NE and other proinflammatory cytokines in serum, and rescued animals against endotoxic shock. Collectively, our data demonstrates that NE signaling can initiate NET formation and that nanoparticle-mediated inhibition of NE improves drug efficacy for preventing NET formation.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: April 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 238〈/p〉 〈p〉Author(s): Xuewen He, Chen Peng, Sujing Qiang, Ling-Hong Xiong, Zheng Zhao, Zaiyu Wang, Ryan T.K. Kwok, Jacky W.Y. Lam, Nan Ma, Ben Zhong Tang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Nanomaterials with integrated multiple imaging and therapeutic modalities possess great potentials in accurate cancer diagnostics and enhanced therapeutic efficacy. Traditional strategies for achieving multimodality nanoplatform through one by one combination of different modalities are challenged by the complicated structural design and fabrication as well as inherent incompatibility between different modalities. Herein, a novel strategy is presented to realize multimodal imaging and synergistic therapy using a class of simple silver core/AIE (aggregation-induced emission) shell nanoparticles. In addition to the intrinsic AIE fluorescence (FL) and metal-based computed tomography (CT) and radiation therapy (RT) properties, an extra functionality at the core/shell interface was identified to enable excellent photothermal (PT) and photoacoustic (PA) performance. As a result, five imaging and therapy modalities (FL, CT, PA, photothermal therapy (PTT), and RT) were achieved with a single structural unit for sensitive tumor imaging and effective therapy.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉A “less is more” strategy is presented to realize multifunctionality within a simple silver core/AIE shell nanoparticle. Apart from their intrinsic AIE fluorescence and noble metal based computed tomography properties, an extra interface with excellent photothermal and photoacoustic functionalities was 〈em〉in situ〈/em〉 generated between the core and shell part, enabling multimodality tumor imaging and synergistic therapy.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0142961220300806-fx1.jpg" width="378" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: April 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 238〈/p〉 〈p〉Author(s): Li-Zhen Zheng, Jia-Li Wang, Jian-Kun Xu, Xiao-Tian Zhang, Bao-Yi Liu, Le Huang, Ri Zhang, Hai-Yue Zu, Xuan He, Jie Mi, Qian-Qian Pang, Xin-Luan Wang, Ye-Chun Ruan, De-Wei Zhao, Ling Qin〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Magnesium (Mg)-based biometal attracts clinical applications due to its biodegradability and beneficial biological effects on tissue regeneration, especially in orthopaedics, yet the underlying anabolic mechanisms in relevant clinical disorders are lacking. The present study investigated the effect of magnesium (Mg) and vitamin C (VC) supplementation for preventing steroid-associated osteonecrosis (SAON) in a rat experimental model. In SAON rats, 50 mg/kg Mg, or 100 mg/kg VC, or combination, or water control was orally supplemented daily for 2 or 6 weeks respectively. Osteonecrosis was evaluated by histology. Serum Mg, VC, and bone turnover markers were measured. Microfil-perfused samples prepared for angiography and trabecular architecture were evaluated by micro-CT. Primary bone marrow cells were isolated from each group to evaluate their potentials in osteoblastogenesis and osteoclastogenesis. The mechanisms were tested 〈em〉in vitro〈/em〉. Histological evaluation showed SAON lesions in steroid treated groups. Mg and VC supplementation synergistically reduced the apoptosis of osteocytes and osteoclast number, and increased osteoblast surface. VC supplementation significantly increased the bone formation marker PINP, and the combination significantly decreased the bone resorption marker CTX. TNFα expression and oxidative injury were decreased in bone marrow in Mg/VC/combination group. Mg significantly increased the blood perfusion in proximal tibia and decreased the leakage particles in distal tibia 2 weeks after SAON induction. VC significantly elevated the osteoblast differentiation potential of marrow cells and improved the trabecular architecture. The combination supplementation significantly inhibited osteoclast differentiation potential of marrow cells. 〈em〉In vitro〈/em〉 study showed promoting osteoblast differentiation effect of VC, and anti-inflammation and promoting angiogenesis effect of Mg with underlying mechanisms. Mg and VC supplementation could synergistically alleviate SAON in rats, indicating great translational potentials of metallic minerals for preventing SAON.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 233〈/p〉 〈p〉Author(s): 〈/p〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 235〈/p〉 〈p〉Author(s): Anup Tuladhar, Jaclyn M. Obermeyer, Samantha L. Payne, Ricky C.W. Siu, Sohrab Zand, Cindi M. Morshead, Molly S. Shoichet〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Therapeutic delivery to the brain is limited by the blood-brain barrier and is exacerbated by off-target effects associated with systemic delivery, thereby precluding many potential therapies from even being tested. Given the systemic side effects of cyclosporine and erythropoietin, systemic administration would be precluded in the context of stroke, leaving only the possibility of local delivery. We wondered if direct delivery to the brain would allow new reparative therapeutics, such as these, to be identified for stroke. Using a rodent model of stroke, we employed an injectable drug delivery hydrogel strategy to circumvent the blood-brain barrier and thereby achieved, for the first time, local and sustained co-release to the brain of cyclosporine and erythropoietin. Both drugs diffused to the sub-cortical neural stem and progenitor cell (NSPC) niche and were present in the brain for at least 32 days post-stroke. Each drug had a different outcome on brain tissue: cyclosporine increased plasticity in the striatum while erythropoietin stimulated endogenous NSPCs. Only their co-delivery, but not either drug alone, accelerated functional recovery and improved tissue repair. This platform opens avenues for hitherto untested therapeutic combinations to promote regeneration and repair after stroke.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 234〈/p〉 〈p〉Author(s): Ting Li, Qiong Wu, Wei Wang, Zengzhen Chen, Longfei Tan, Jie Yu, Changhui Fu, Xiangling Ren, Ping Liang, Jun Ren, Limin Ma, Xianwei Meng〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Microwave (MW) thermal therapy has been vigorously developed in recent years because of its better therapeutic efficiency and smaller side effects compared with traditional tumor treatment methods. In order to promote the tumor cell apoptosis under MW irradiation and achieve better therapeutic effect and prognosis, various microwave sensitizers have been developed. Metal organic frameworks (MOFs) have become one of the most popular materials for microwave sensitization due to their diverse morphology, porous surface and good biodegradability. However, the harsh preparation conditions and long growth time are insurmountable shortcomings of MOFs. Besides, the spongy porous structure of MOFs is not conducive to the retention of ions, leading to insufficient friction and collision between ions under MW radiation. Herein, we synthesized a kind of open-mouthed Zr MOF-derived nano-popcorns (ZDNPs) with the size of about 250 nm by a rapid sonochemical aerosol flow strategy. Compared with UIO-66, the open-mouthed ZDNPs have a better ability to entrap more ions due to their big cracks on the surface, thus improving their MW sensitization performance. The MW heating experiments 〈em〉in vitro〈/em〉 present that the net temperature change value of ZDNP was 120% higher than UIO-66 at the same concentration, proving that ZDNP had a higher MW-thermo conversion efficiency than UIO-66, which provided an unprecedented direction for the exploration of more diversified MW sensitizers.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 235〈/p〉 〈p〉Author(s): Yoshiki Takeoka, Takashi Yurube, Koichi Morimoto, Saori Kunii, Yutaro Kanda, Ryu Tsujimoto, Yohei Kawakami, Naomasa Fukase, Toshiyuki Takemori, Kaoru Omae, Yuji Kakiuchi, Shingo Miyazaki, Kenichiro Kakutani, Toru Takada, Kotaro Nishida, Masanori Fukushima, Ryosuke Kuroda〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Back pain is a global health problem with a high morbidity and socioeconomic burden. Intervertebral disc herniation and degeneration are its primary cause, further associated with neurological radiculopathy, myelopathy, and paralysis. The current surgical treatment is principally discectomy, resulting in the loss of spinal movement and shock absorption. Therefore, the development of disc regenerative therapies is essential. Here we show reduced disc damage by a new collagen type I-based scaffold through actinidain hydrolysis—Low Adhesive Scaffold Collagen (LASCol)—with a high 3D spheroid-forming capability, water-solubility, and biodegradability and low antigenicity. In human disc nucleus pulposus and annulus fibrosus cells surgically obtained, time-dependent spheroid formation with increased expression of phenotypic markers and matrix components was observed on LASCol but not atelocollagen (AC). In a rat tail nucleotomy model, LASCol-injected and AC-injected discs presented relatively similar radiographic and MRI damage control; however, LASCol, distinct from AC, decelerated histological disc disruption, showing collagen type I-comprising LASCol degradation, aggrecan-positive and collagen type II-positive endogenous cell migration, and M1-polarized and also M2-polarized macrophage infiltration. Reduced nucleotomy-induced disc disruption through spontaneous spheroid formation by LASCol warrants further investigations of whether it may be an effective treatment without stem cells and/or growth factors for intervertebral disc disease.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 234〈/p〉 〈p〉Author(s): Yamin Li, Zachary Glass, Mingqian Huang, Zheng-Yi Chen, Qiaobing Xu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The recently developed CRISPR/Cas9 technology has revolutionized the genome engineering field. Since 2016, increasing number of studies regarding CRISPR therapeutics have entered clinical trials, most of which are focusing on the 〈em〉ex vivo〈/em〉 genome editing. In this review, we highlight the 〈em〉ex vivo〈/em〉 cell-based CRISPR/Cas9 genome editing for therapeutic applications. In these studies, CRISPR/Cas9 tools were used to edit cells i〈em〉n vitro〈/em〉 and the successfully edited cells were considered as therapeutics, which can be introduced into patients to treat diseases. Considering a large number of previous reviews have been focused on the CRISPR/Cas9 delivery methods and materials, this review provides a different perspective, by mainly introducing the targeted conditions and design strategies for 〈em〉ex vivo〈/em〉 CRISPR/Cas9 therapeutics. Brief descriptions of the history, functionality, and applications of CRISPR/Cas9 systems will be introduced first, followed by the design strategies and most significant results from previous research that used 〈em〉ex vivo〈/em〉 CRISPR/Cas9 genome editing for the treatment of conditions or diseases. The last part of this review includes general information about the status of CRISPR/Cas9 therapeutics in clinical trials. We also discuss some of the challenges as well as the opportunities in this research area.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 233〈/p〉 〈p〉Author(s): Zhenhui Lu, Sijia Liu, Yiguan Le, Zainen Qin, Mingwei He, Fuben Xu, Ye Zhu, Jinmin Zhao, Chuanbin Mao, Li Zheng〈/p〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 234〈/p〉 〈p〉Author(s): Jian He, Yue Qiao, Hongbo Zhang, Jun Zhao, Wanli Li, Tingting Xie, Danni Zhong, Qiaolin Wei, Shiyuan Hua, Yinhui Yu, Ke Yao, Hélder A. Santos, Min Zhou〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Chronic infections, caused by multidrug-resistant (MDR) bacteria, constitute a serious problem yet often underappreciated in clinical practice. The in situ monitoring of the bacteria-infected disease is also necessary to track and verify the therapeutic effect. Herein we present a facile approach to overcome the above challenges through a Raman tag 3,3′-diethylthiatricarbocyanine iodide (DTTC)-conjugated gold-silver nanoshells (AuAgNSs). With a strong responsive of the near-infrared laser due to surface plasmon resonance (SPR) from hybrid metallic nanoshell structure, AuAgNSs exhibits an efficient photothermal effect, and it simultaneously releases silver ions during laser irradiation to bacterial eradicate. Herein, two MDR bacteria strain, methicillin-resistant 〈em〉Staphylococcus aureus〈/em〉 (MRSA) and extended-spectrum β-lactamase 〈em〉Escherichia coli〈/em〉, are chosen as models and studied both in vitro and in vivo. As a result, the AuAgNSs-DTTC substrates enable surface-enhanced Raman scattering imaging to provide a non-invasive and extremely high sensitive detection (down to 300 CFU mL〈sup〉−1〈/sup〉 for MRSA) and prolonged tracking (at least 8 days) of residual bacteria. In a chronic MRSA-infected wound mouse model, the AuAgNSs gel-mediated photothermal therapy/silver-release leads to a synergistic would healing with negligible toxicity or collateral damage to vital organs. These results suggest that AuAgNSs-DTTC is a promising anti-bacterial tool for clinical translation.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉3,3′-diethylthiatricarbocyanine iodide (DTTC)-conjugated gold-silver nanoshell (AuAg) nanosystems are fabricated to enable surface-enhanced Raman scattering imaging and photothermal eradication to multidrug-resistant bacteria. Remarkably, the designed nanostructures provide a non-invasive and highly sensitive detection (down to 300 CFU mL〈sup〉−1〈/sup〉 for MRSA) and prolonged tracking (at least 8 days) of residual bacteria during wound healing.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0142961220300090-fx1.jpg" width="500" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 234〈/p〉 〈p〉Author(s): Wei-Hung Jung, Nicholas Yam, Chin-Chi Chen, Khalid Elawad, Brian Hu, Yun Chen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉It is known cancer cells secrete cytokines inducing normal fibroblasts (NFs) to become carcinoma-associated fibroblasts (CAFs). However, it is not clear how the CAF-promoting cytokines can effectively navigate the dense ECM, a diffusion barrier, in the tumor microenvironment to reach NFs during the early stages of cancer development. In this study, we devised a 3D coculture system to investigate the possible mechanism of CAF induction at early stages of breast cancer. We found that in a force-dependent manner, ECM fibrils are radially aligned relative to the tumor spheroid. The fibril alignment enhances the diffusion of exosomes containing CAF-promoting cytokines towards NFs. Suppression of force generation or ECM remodeling abolishes the enhancement of exosome diffusion and the subsequent CAF induction. In summary, our finding suggests that early-stage, pre-metastatic cancer cells can generate high forces to align the ECM fibrils, thereby enhancing the diffusion of CAF-promoting exosomes to reach the stroma and induce CAFs.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: February 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 232〈/p〉 〈p〉Author(s): Conglian Yang, Kun Tu, Hanlu Gao, Liao Zhang, Yu Sun, Ting Yang, Li Kong, Defang Ouyang, Zhiping Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Herein, a small library of Pt(IV) prodrugs based on cisplatin and chemosensitizer adjudin (ADD) were explored for efficient cisplatin resistant triple-negative breast cancer (TNBC) treatment. We further elucidated the detail relationship of chemical structure, alkyl chain length (ethyl to dodecyl) and ADD substituted degree, with respect to the self-assembly ability and cytotoxic effect of prodrugs. It demonstrated that all prodrugs could self-assemble into nanomedicine, which was in consist with the molecule structure building and self-assembly simulation. All nanomedicines possessed small particle size, uniform morphology and ultra-high drug loading content (84.0%–86.5%). Moreover, the length of alkyl chain was of great importance for the structure-transformable character and cytotoxicity of nanomedicines. Interestingly, ADD monosubstituted with butyl or hexyl contralateral substituted prodrug (C〈sub〉4〈/sub〉-Pt-ADD or C〈sub〉6〈/sub〉-Pt-ADD) assembled nanomedicine could convert to wire or sheet structure. These transformable nanoparticles showed great potential in improving the sensitivity of cisplatin to TNBC with up to 266-fold lower IC〈sub〉50〈/sub〉 value and significantly enhanced 〈em〉in vivo〈/em〉 tumor growth inhibition. Therefore, the self-assembled nanomedicine based on Pt(IV)-ADD could be a promising strategy for TNBC therapy.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉A series of self-assembled nanomedicine based on Pt(IV)-ADD prodrug were fabricated here for cisplatin resistant triple-negative breast cancer (TNBC) therapy. Interestingly, the length of alkyl chain was of great importance for the structure-transformable character and cytotoxicity of nanomedicines. ADD monosubstituted with butyl or hexyl contralateral substituted prodrug (C〈sub〉4〈/sub〉-Pt-ADD or C〈sub〉6〈/sub〉-Pt-ADD) assembled nanomedicine could convert to wire or sheet structure. These transformable nanoparticles showed great potential in improving cisplatin sensitive to TNBC with up to 266-fold lower IC〈sub〉50〈/sub〉 value and significantly enhanced 〈em〉in vivo〈/em〉 tumor growth inhibition.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0142961219308695-fx1.jpg" width="281" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 233〈/p〉 〈p〉Author(s): Yesi Shi, Junqing Wang, Jingyi Liu, Gan Lin, Fengfei Xie, Xin Pang, Yihua Pei, Yi Cheng, Yang Zhang, Zhongning Lin, Zhengyu Yin, Xiaomin Wang, Gang Niu, Xiaoyuan Chen, Gang Liu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉There exists an emergency clinical demand to overcome TRAIL/Apo2L (tumor necrosis factor-related apoptosis-inducing ligand) resistance, which is a major obstacle attributed to insufficient level or mutation of TRAIL receptors. Here, we developed an iron oxide cluster-based nanoplatform for both sensitization and MR image-guided evaluation to improve TRAIL/Apo2L efficacy in colorectal cancer, which has an inadequate response to TRAIL/Apo2L or chemotherapy. Specifically, NanoTRAIL (TRAIL/Apo2L-iron oxide nanoparticles) generated ROS (reactive oxygen species)-triggered JNK (c-Jun N-terminal kinase) activation and induced subsequent autophagy-assisted DR5 upregulation, resulting in a significant enhanced antitumor efficacy of TRAIL/Apo2L, which confirmed in both TRAIL-resistant HT-29, intermediately resistant SW-480 and sensitive HCT-116 cells. Furthermore, in a subcutaneous colorectal cancer mouse model, the 〈em〉in vivo〈/em〉 tumor retention of NanoTRAIL can be demonstrated by MR 〈em〉T〈/em〉〈sub〉2〈/sub〉 weighted contrast imaging, and NanoTRAIL significantly suppressed tumor growth and prolonged the survival time without observable adverse effects compared with control and TRAIL/Apo2L monotherapy. Importantly, in the study of colorectal cancer patient-derived xenograft models, we found that the NanoTRAIL treatment could significantly improve the survival outcome with consistent ROS-dependent autophagy-assisted DR5 upregulation and tumor apoptosis. Our results describe a transformative design that can be applied clinically to sensitize Apo2L/TRAIL-resistant patients using FDA-approved iron oxide nanoparticles.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 233〈/p〉 〈p〉Author(s): Olya Mastikhina, Byeong-Ui Moon, Kenneth Williams, Rupal Hatkar, Dakota Gustafson, Omar Mourad, Xuetao Sun, Margaret Koo, Alan Y.L. Lam, Yu Sun, Jason E. Fish, Edmond W.K. Young, Sara S. Nunes〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉While interstitial fibrosis plays a significant role in heart failure, our understanding of disease progression in humans is limited. To address this limitation, we have engineered a cardiac-fibrosis-on-a-chip model consisting of a microfabricated device with live force measurement capabilities using co-cultured human cardiac fibroblasts and pluripotent stem cell-derived cardiomyocytes. Transforming growth factor-β was used as a trigger for fibrosis. Here, we have reproduced the classic hallmarks of fibrosis-induced heart failure including high collagen deposition, increased tissue stiffness, BNP secretion, and passive tension. Force of contraction was significantly decreased in fibrotic tissues that displayed a transcriptomic signature consistent with human cardiac fibrosis/heart failure. Treatment with an anti-fibrotic drug decreased tissue stiffness and BNP secretion, with corresponding changes in the transcriptomic signature. This model represents an accessible approach to study human heart failure 〈em〉in vitro〈/em〉, and allows for testing anti-fibrotic drugs while facilitating the real-time assessment of cardiomyocyte function.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0142961219308592-fx1.jpg" width="441" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: February 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 232〈/p〉 〈p〉Author(s): Rongrong Ni, Guojing Song, Xiaohong Fu, Ruifeng Song, Lanlan Li, Wendan Pu, Jining Gao, Jun Hu, Qin Liu, Fengtian He, Dinglin Zhang, Gang Huang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease that results in synovitis, cartilage destruction, and even loss of joint function. The frequent and long-term administration of anti-rheumatic drugs often leads to obvious adverse effects and patient non-compliance. Therefore, to specifically deliver dexamethasone (Dex) to inflamed joints and reduce the administration frequency of Dex, we developed Dex-loaded reactive oxygen species (ROS)-responsive nanoparticles (Dex/Oxi-αCD NPs) and folic acid (FA) modified Dex/Oxi-αCD NPs (Dex/FA-Oxi-αCD NPs) and validated their anti-inflammatory effect 〈em〉in vitro〈/em〉 and 〈em〉in vivo〈/em〉. 〈em〉In vitro〈/em〉 study demonstrated that these NPs can be effectively internalized by activated macrophages and the released Dex from NPs significantly downregulated the expression of iRhom2, TNF-α, and BAFF in activated Raw264.7. 〈em〉In vivo〈/em〉 experiments revealed that Dex/Oxi-αCD NPs, especially Dex/FA-Oxi-αCD NPs significantly accumulated at inflamed joints in collagen-induced arthritis (CIA) mice and alleviated the joint swelling and cartilage destruction. Importantly, the expression of iRhom2, TNF-α, and BAFF in the joint was inhibited by intravenous injection of Dex/Oxi-αCD NPs and Dex/FA-Oxi-αCD NPs. Collectively, our data revealed that Dex-loaded ROS-responsive NPs can target inflamed joints and attenuate arthritis, and the ‘iRhom2-TNF-α-BAFF’ pathway plays an important role in the treatment of RA with the NPs, suggesting that this pathway may be a novel target for RA therapy.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 24 February 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Sean H. Kelly, Yaoying Wu, Ajay K. Varadhan, Elizabeth J. Curvino, Anita S. Chong, Joel H. Collier〈/p〉

Description: 〈p〉Publication date: Available online 24 February 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Wei Hu, Lingyu Zeng, Shuyang Zhai, Chenchen Li, Wenqi Feng, Yang Feng, Zhihong Liu〈/p〉

Description: 〈p〉Publication date: Available online 25 February 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Yu-Jing He, Xiao-Ying Liu, Lei Xing, Xing Wan, Xin Chang, Hu-Lin Jiang〈/p〉

Description: 〈p〉Publication date: Available online 21 February 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Silvia Sanchez-Casanova, Francisco M. Martin-Saavedra, Clara Escudero-Duch, Maria I. Falguera Uceda, Martin Prieto, Manuel Arruebo, Paloma Acebo, Mario L. Fabiilli, Renny T. Franceschi, Nuria Vilaboa〈/p〉

Description: 〈p〉Publication date: May 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 241〈/p〉 〈p〉Author(s): Xiaokun Wang, Shoumyo Majumdar, Uri Soiberman, Joshua N. Webb, Liam Chung, Giuliano Scarcelli, Jennifer H. Elisseeff〈/p〉

Description: 〈p〉Publication date: May 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 240〈/p〉 〈p〉Author(s): Jip Zonderland, Ivan Lorenzo Moldero, Shivesh Anand, Carlos Mota, Lorenzo Moroni〈/p〉

Description: 〈p〉Publication date: May 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 240〈/p〉 〈p〉Author(s): Jie Zhao, Zesen Ye, Jun Yang, Qiang Zhang, Wenjun Shan, Xiumin Wang, Zhanxiang Wang, Shefang Ye, Xi Zhou, Zhicheng Shao, Lei Ren〈/p〉

Description: 〈p〉Publication date: May 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 239〈/p〉 〈p〉Author(s): Wenzhen Pan, Chengbai Dai, Yang Li, Yiming Yin, Ling Gong, Jeremiah Ong'achwa Machuki, Yun Yang, Shang Qiu, Kaijin Guo, Fenglei Gao〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease causing destruction of bone and cartilago articularis. Traditional treatment methods have many side effects, or too concerne about the anti-inflammatory mechanisms but ignore osteanagenesis. In this work, a novel therapeutic platform combined black phosphorus nanosheets (BPNs) into platelet-rich plasma (PRP)-chitosan thermoresponsive hydrogel has been prepared for management of RA. The BPNs generate local heat upon near-infrared irradiation, and delivering reactive oxygen species (ROS) to the inflamed joints simultaneously for removing hyperplastic synovial tissue. The injectable chitosan thermoresponsive hydrogel can take control of the releasing of BPNs degradation products, which provide ample raw materials for osteanagenesis. In addition, the PRP can effectively improve the adhesion and increase capacity of mesenchymal stem cells on chitosan thermosensitive hydrogels. And this thermoresponsive hydrogel can protect articular cartilage by reducing the friction on the surrounding tissue. Drug delayed release property was indicated by the release and uptake of methotrexate. The edema degree of the arthritic mouse was reduced obviously by the BPNs/Chitosan/PRP thermoresponsive hydrogel. Both in vitro and in vivo studies suggest that the thermoresponsive hydrogel can provide a potential possibility for the management of RA.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: May 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 240〈/p〉 〈p〉Author(s): Shuang Liang, Chunqiang Sun, Piaoping Yang, Ping'an Ma, Shanshan Huang, Ziyong Cheng, Xifei Yu, Jun Lin〈/p〉

Description: 〈p〉Publication date: May 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 239〈/p〉 〈p〉Author(s): Ellen C. Qin, Syeda T. Ahmed, Poonam Sehgal, Vinh H. Vu, Hyunjoon Kong, Deborah E. Leckband〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The recent interest in exploiting cadherin-derived fragments to mimic intercellular adhesion in engineered hybrid biomaterials raises questions about which cadherin constructs effectively mimic cadherin interactions. This study compared the biophysical properties of and signaling initiated by three different, immobilized N-cadherin-derived fragments, in order to identify a minimal construct that mimics intercellular adhesion in biomaterials. Specifically, we compared: i) the full N-cadherin extracellular region with all five ectodomains (EC1-5), ii) the first two ectodomains (EC1-2) of N-cadherin, and iii) a peptide containing the histidine-alanine-valine-aspartic acid-valine (HAVDI) sequence in the first extracellular domain. Comparisons of the binding kinetics and affinities between each of these ligands and N-cadherin expressed on mesenchymal stem cells (MSCs) revealed quantitative differences. Nevertheless, MSCs exhibited similar, rigidity-dependent spreading and traction forces when cultured on gels displaying any of these N-cadherin ligands. There were, however, differences in cell signaling and secretory activities. MSCs cultured on the full N-cadherin extracellular domain (EC1-5) exhibited stiffness-dependent changes in nuclear YAP/TAZ localization and significantly higher secretion of vascular endothelial growth factor and insulin growth factor 1, compared to cells cultured on hydrogels displaying either EC1-2 or the HAVDI peptide. The increased paracrine secretion also enhanced myogenic differentiation. These findings reveal functional differences between N-cadherin derived ligands important for the design of biomaterials that mimic intercellular adhesion.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: April 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 238〈/p〉 〈p〉Author(s): Peng Yang, Dongyu Sheng, Qian Guo, Pengzhen Wang, Shuting Xu, Kang Qian, Yixian Li, Yunlong Cheng, Liuchang Wang, Wei Lu, Qizhi Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Mitochondrial dysfunction is an early event of Alzheimer's disease (AD), contributes the onset and progression of AD, and may represent an effective therapeutic target for AD intervention. Since mitochondria in central neurons are more susceptible to oxidative damage than non-neuronal cells, the specific delivery of the antioxidants to the mitochondria of impaired central neurons is crucial for achieving the therapeutic effect on AD. Here, we prepare the neuronal mitochondria-targeted micelles (CT-NM) through co-decoration with neural cell adhesion molecule (NCAM) mimetic peptide C3 for brain neuron specific binding and the triphenylphosphonium (TPP) for mitochondrial targeting. CT-NM significantly increase the encapsulated resveratrol's concentration in the neuronal mitochondria compared to the micelles modified with C3 only or the resveratrol solution. The resveratrol-loaded CT-NM alleviate the oxidative stress in the neuronal cells, resulting in stabilization of the dynamic balance of mitochondrial fission and fusion. The targeted micelles restore the cognitive performance in APP/PS1 transgenic mice to the level of wild-type mice characterized by up-regulation of sirtuin 1 expression, reduction of amyloid deposition and tau hyperphosphorylation, protection of synapses and inhibition of microglia proliferation. The results demonstrate the delay of the progression of AD through reversing neuronal mitochondrial dysfunction by the targeted delivery of antioxidants.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: May 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 240〈/p〉 〈p〉Author(s): Xu Sun, Ziyang Cao, Kuirong Mao, Chenxi Wu, Hongmei Chen, Jialiang Wang, Xin Wang, Xiuxiu Cong, Yong Li, Xianying Meng, Xianzhu Yang, Yong-Guang Yang, Tianmeng Sun〈/p〉

Description: 〈p〉Publication date: May 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 240〈/p〉 〈p〉Author(s): Meilu Dai, Baiyan Sui, Yujie Hua, Yiqing Zhang, Bingkun Bao, Qiuning Lin, Xin Liu, Linyong Zhu, Jiao Sun〈/p〉

Description: 〈p〉Publication date: April 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 238〈/p〉 〈p〉Author(s): Di Wu, Jiajing Zhou, Xiaohong Chen, Yonghao Chen, Shuai Hou, Hehe Qian, Lifeng Zhang, Guping Tang, Zhong Chen, Yuan Ping, Wenjun Fang, Hongwei Duan〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Functional proteins are essential for the regulation of cellular behaviors and have found growing therapeutic uses. However, low bioavailability of active proteins to their intracellular targets has been a long-standing challenge to achieve their full potential for cell reprogramming and disease treatment. Here we report mesoporous polydopamine (mPDA) with a built-in plasmonic nanoparticle core as a multifunctional protein delivery system. The mPDA with a unique combination of large surface area, metal-chelating property, and broad-spectrum photothermal transduction allows efficient loading and near-infrared light-triggered release of functional proteins, while the plasmonic core serves as a photostable tracer and fluorescence quencher, collectively leading to real-time monitoring and active cytosolic release of model proteins. In particular, controlled delivery of cytotoxic ribonuclease A has shown excellent performance in 〈em〉in〈/em〉 〈em〉vivo〈/em〉 cancer therapy. The possibility of coating mPDA on a broad range of functional cores, thanks to its universal adhesion, provides opportunities for developing tailored delivery carriers of biologics to overcome intrinsic biological barriers.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0142961220300934-fx1.jpg" width="441" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: May 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 239〈/p〉 〈p〉Author(s): Steven M. Wellman, Kelly Guzman, Kevin C. Stieger, Lauren E. Brink, Sadhana Sridhar, Mitchell T. Dubaniewicz, Lehong Li, Franca Cambi, Takashi D.Y. Kozai〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Biological inflammation induced during penetrating cortical injury can disrupt functional neuronal and glial activity within the cortex, resulting in potential recording failure of chronically implanted neural interfaces. Oligodendrocytes provide critical support for neuronal health and function through direct contact with neuronal soma and axons within the cortex. Given their fundamental role to regulate neuronal activity via myelin, coupled with their heightened vulnerability to metabolic brain injury due to high energetic demands, oligodendrocytes are hypothesized as a possible source of biological failure in declining recording performances of intracortical microelectrode devices. To determine the extent of their contribution to neuronal activity and function, a cuprizone-inducible model of oligodendrocyte depletion and demyelination in mice was performed prior to microelectrode implantation. At 5 weeks of cuprizone exposure, mice demonstrated significantly reduced cortical oligodendrocyte density and myelin expression. Mice were then implanted with functional recording microelectrodes in the visual cortex and neuronal activity was evaluated up to 7 weeks alongside continued cuprizone administration. Cuprizone-induced oligodendrocyte loss and demyelination was associated with significantly reduced recording performances at the onset of implantation, which remained relatively stable over time. In contast, recording performances for mice on a normal diet were intially elevated before decreasing over time to the recording level of tcuprizone-treated mice. Further electrophysiological analysis revealed deficits in multi-unit firing rates, frequency-dependent disruptions in neuronal oscillations, and altered laminar communication within the cortex of cuprizone-treated mice. Post-mortem immunohistochemistry revealed robust depletion of oligodendrocytes around implanted microelectrode arrays alongside comparable neuronal densities to control mice, suggesting that oligodendrocyte loss was a possible contributor to chronically impaired device performances. This study highlights potentially significant contributions from the oligodendrocyte lineage population concerning the biological integration and long-term functional performance of neural interfacing technology.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 29 January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Yanzhen Li, Daniel Song, Lan Mao, Dennis M. Abraham, Nenad Bursac〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In response to heart injury, inflammation, or mechanical overload, quiescent cardiac fibroblasts (CFs) can become activated myofibroblasts leading to pathological matrix remodeling and decline in cardiac function. Specific targeting of fibroblasts may thus enable new therapeutic strategies to delay or reverse the progression of heart failure and cardiac fibrosis. However, it remains unknown if all CFs are equally responsive to specific pathological insults and if there exist sub-populations of resident fibroblasts in the heart that have distinctive pathogenic phenotypes. Here, we show that in response to transverse aortic constriction (TAC)-induced heart failure, previously uncharacterized Thy1〈sup〉neg〈/sup〉 (Thy1-/MEFSK4+/CD45-/CD31-) fraction of mouse ventricular fibroblasts became more abundant and attained a more activated, pro-fibrotic myofibroblast phenotype compared to Thy1〈sup〉Pos〈/sup〉 fraction. In a tissue-engineered 3D co-culture model of healthy cardiomyocytes and freshly isolated CFs, Thy1〈sup〉neg〈/sup〉 CFs from TAC hearts significantly decreased cardiomyocyte contractile function and calcium transient amplitude, and increased extracellular collagen deposition yielding a profibrotic heart tissue phenotype. 〈em〉In vivo〈/em〉, mice with global knockout of Thy1 developed more severe cardiac dysfunction and fibrosis in response to TAC-induced heart failure than wild-type mice. Taken together, our studies identify cardiac myofibroblasts lacking Thy1 as a pathogenic CF fraction in cardiac fibrosis and suggest important roles of Thy1 in pathophysiology of heart failure.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 28 January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials〈/p〉 〈p〉Author(s): Guohao Wang, Lin Song, Xuandi Hou, Shashwati Kala, Kin Fung Wong, Liya Tang, Yunlu Dai, Lei Sun〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Nanobubbles, as a kind of new ultrasound contrast agent (UCAs), have shown promise to penetrate tumor vasculature to allow for targeted imaging. However, their inherent physical instability is an ongoing concern that could weaken their imaging ability with ultrasound. Gas vesicles (GVs), which are genetically encoded, naturally stable nanostructures, have been developed as the first ultrasonic biomolecular reporters which showed strong contrast enhancement. However, further development of tumor imaging with GVs is limited by the quick clearance of GVs by the reticuloendothelial system (RES). Here, we developed PEGylated HA-GVs (PH-GVs) for in-tumor molecular ultrasound imaging by integrating polyethylene glycol (PEG) and hyaluronic acid (HA) in GV shells. PH-GVs were observed to accumulate around CD44-positive cells (SCC7) but not be internalized by macrophage cell line RAW 264.7. Green fluorescence from PH-GVs was found around cell nuclei in the tumor site after 6 h and the signal was sustained over 48 h following tail injection, demonstrating PH-GVs’ ability to escape the clearance from the RES and to penetrate tumor vasculature through enhanced permeability and retention (EPR) effects. Further, PH-GVs produced strong ultrasound contrast in the tumor site 〈em〉in vivo〈/em〉, with no obvious side-effects detected following intravenous injection. Thus, we demonstrate the potential of PH-GVs as novel, nanosized and targeted UCAs for efficient and specific molecular tumor imaging, paving the way for the application of GVs in precise and personalized medicine.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0142961220300491-fx1.jpg" width="373" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉