Journal Sciences News
Toxicology
March 2018
Engineered cardiac tissue patch maintains structural and electrical properties after epicardial implantation
Publication date: March 2018
Source:Biomaterials, Volume 159 Author(s): Christopher P. Jackman, Asvin M. Ganapathi, Huda Asfour, Ying Qian, Brian W. Allen, Yanzhen Li, Nenad Bursac Functional cardiac tissue engineering holds promise as a candidate therapy for myocardial infarction and heart failure. Generation of ôstrong-contracting and fast-conductingö cardiac tissue patches capable of electromechanical coupling with host myocardium could allow efficient improvement of heart function without increased arrhythmogenic risks. Towards that goal, we engineered highly functional 1
March 2018
Realizing highly chemoselective detection of H2S inávitro and inávivo with fluorescent probes inside core-shell silica nanoparticles
Publication date: March 2018
Source:Biomaterials, Volume 159 Author(s): Feiyi Wang, Ge Xu, Xianfeng Gu, Zhijun Wang, Zhiqiang Wang, Ben Shi, Cuifen Lu, Xueqing Gong, Chunchang Zhao Hydrogen sulfide (H2S) is an appealing signaling molecule that plays fundamental roles in health and disease. However, H2S-mediated selective chemical transformations for the construction of imaging probes are limited, retarding the interrogation of H2S-related biological processes. Here, we present an alternative approach for engineering a new generation of efficient probes with a nonchemoselective moiety as a building block. To demonstrate our design concept, we developed a sulfoxide-functionalized BODIPY that exhibited a substantial redshift in its absorption and emission spectra upon reduction with H2S. However, such a probe also showed reactivity toward various competing biothiols under aqueous buffer conditions. To achieve high chemoselectivity, we used core-shell silica nanoparticles as an encapsulation matrix to confine the designed molecule probe within their interiors. The inherent molecular-size sieving character of the porous silica shell was capable of impeding competing biothiols from accessing the molecule probe within the core while allowing the specific reaction with the small target H2S. Thus, this strategy avoided disturbance from coexisting biothiols and achieved highly chemoselective detection in ratiometric and near-infrared (NIR) turn-on fluorescence modes. In light of these promising features, together with fast responsiveness and favorable cellular uptake, such a silica nanocomposite was successfully used to detect the endogenous production of H2S in estrogen-induced cardiomyocytes and living mouse model. To our knowledge, the approach reported here is the first to exploit the usefulness of common thiol-sensitive moieties for building chemoselective probes.

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March 2018
Simultaneous three-dimensional visualization of mineralized and soft skeletal tissues by a novel microCT contrast agent with polyoxometalate structure
Publication date: March 2018
Source:Biomaterials, Volume 159 Author(s): Greet Kerckhofs, Steve Stegen, Nick van Gastel, Annelies Sap, Guillaume Falgayrac, Guillaume Penel, Marjorie Durand, Frank P. Luyten, Liesbet Geris, Katleen Vandamme, Tatjana Parac-Vogt, Geert Carmeliet Biological tissues have a complex and heterogeneous 3D structure, which is only partially revealed by standard histomorphometry in 2D. We here present a novel chemical compound for contrast-enhanced microfocus computed tomography (CE-CT), a Hafnium-based Wells-Dawson polyoxometalate (Hf-POM), which allows simultaneous 3D visualization of mineralized and non-mineralized skeletal tissues, such as mineralized bone and bone marrow vasculature and adipocytes. We validated the novel contrast agent, which has a neutral pH in solution, by detailed comparison with (immuno)histology on murine long bones as blueprint, and showed that Hf-POM-based CE-CT can be used for virtual 3D histology. Furthermore, we quantified the 3D structure of the different skeletal tissues, as well as their spatial relation to each other, during aging and diet-induced obesity. We discovered, based on a single CE-CT dataset per sample, clear differences between the groups in bone structure, vascular network organization, characteristics of the adipose tissue and proximity of the different tissues to each other. These findings highlight the complementarity and added value of Hf-POM-based CE-CT compared to standard histomorphometry. As this novel technology provides a detailed 3D simultaneous representation of the structural organization of mineralized bone and bone marrow vasculature and adipose tissue, it will enable to improve insight in the interactions between these three tissues in several bone pathologies and to evaluate the inávivo performance of biomaterials for skeletal regeneration.

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March 2018
Platelet membrane coating coupled with solar irradiation endows a photodynamic nanosystem with both improved antitumor efficacy and undetectable skin damage
Publication date: March 2018
Source:Biomaterials, Volume 159 Author(s): Lulu Xu, Feng Gao, Feng Fan, Lihua Yang The therapeutic efficacy of tumor photodynamic therapy (PDT) is hindered by the following three challenges. The extremely short lifetime of reactive oxygen species (ROS, the cytotoxic factor of PDT) limits the radius of their action to tens-of-nanometer scale; functionalizing a photodynamic nanosystem with active targeting moieties helps bring the target cells into reach of ROS but requires extra research efforts. Current photodynamic systems are in general excited by light on the short end of near-infrared (NIR) region; deep tissue penetration necessitates the development of those excitable by longer NIR light. Reducing irradiation dose is necessary for avoiding skin damages but impacts the therapeutic outcome; how to resolve this delimma remains a challenge. We herein show that platelet membrane-coating over a photodynamic nanoparticle coupled with solar irradiation may simultaneously resolve all challenges above. Platelet membrane-coating provides both long circulation and active targeting, leading to preferential internalization by tumor over fibroblast cells inávitro and higher tumor uptake than the red blood cell (RBC) membrane-coated counterpart. Preloading a photodynamic sensitizer into a synthetic nanocarrier shifts its absorption peak to longer wavelength, which favors deep tissue penetration. Upon irradiation with NIR light from a solar simulator at extremely low output power density, the platelet membrane-coated photodynamic-nanoparticle outperforms its RBC membrane-coated counterpart and effectively ablates tumor without causing skin damages, which underscores the importance of active targeting in tumor PDT. We anticipate that platelet membrane coating may facilitate the inávivo applications of antitumor photodynamic therapy.
March 2018
Injectable thermogel for 3D culture of stem cells
Publication date: March 2018
Source:Biomaterials, Volume 159 Author(s): Madhumita Patel, Hyun Jung Lee, Sohee Park, Yelin Kim, Byeongmoon Jeong Thermogel is an aqueous polymer solution that undergoes sol-to-gel transition as the temperature increases. Cells, growth factors, and signaling molecules can be incorporated simultaneously during the sol-to-gel transition. The cytocompatible procedure makes the thermogel an excellent platform for 3D culture of stem cells. This review focuses on the crucial questions that need to be addressed to achieve effective differentiation of stem cells into target cells, comprising low modulus, cell adhesion, and controlled supply of the growth factors. Recent progress in the use of thermogel as a 3D culture system of stem cells is summarized, and our perspectives on designing a new thermogel for 3D culture and its eventual application to injectable tissue engineering of stem cells are presented.

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March 2018
Ex-vivo generation of drug-eluting islets improves transplant outcomes by inhibiting TLR4-Mediated NFkB upregulation
Publication date: March 2018
Source:Biomaterials, Volume 159 Author(s): Charles A. Chang, Babatope Akinbobuyi, Jeremy M. Quintana, Gumpei Yoshimatsu, Bashoo Naziruddin, Robert R. Kane The systemic administration of immunosuppressive and anti-inflammatory drugs is routinely employed in organ transplantation to minimize graft rejection and improve graft survival. Localized drug delivery has the potential to improve transplant outcomes by providing sustained exposure to efficacious drug concentrations while avoiding systemic immunosuppression and off-target effects. Here, we describe the synthesis of a novel prodrug and its direct covalent conjugation to pancreatic islets via a cleavable linker. Post-transplant, linker hydrolysis results in the release of a potent anti-inflammatory antagonist of TLR4, localized to the site of implantation. This covalent islet modification significantly reduces the time and the minimal effective dose of islets necessary to achieve normoglycemia in a murine transplantation model. In streptozotocin-induced diabetic C57BL/6 mice a syngeneic transplant of
March 2018
Degradable rhenium trioxide nanocubes with high localized surface plasmon resonance absorbance like gold for photothermal theranostics
Publication date: March 2018
Source:Biomaterials, Volume 159 Author(s): Wenlong Zhang, Guoying Deng, Bo Li, Xinxin Zhao, Tao Ji, Guosheng Song, Zhiyin Xiao, Qing Cao, Jingbo Xiao, Xiaojuan Huang, Guoqiang Guan, Rujia Zou, Xinwu Lu, Junqing Hu The applications of inorganic theranostic agents in clinical trials are generally limited to their innate non-biodegradability and potential long-term biotoxicity. To address this problem, herein via a straightforward and tailored space-confined on-substrate route, we obtained rhenium trioxide (ReO3) nanocubes (NCs) that display a good biocompatibility and biosafety. Importantly, their aqueous dispersion has high localized surface plasmon resonance (LSPR) absorbance in near-infrared (NIR) region different from previous report, which possibly associates with the charge transfer and structural distortion in hydrogen rhenium bronze (HxReO3), as well as ReO3's cubic shape. Such a high LSPR absorbance in the NIR region endows them with photoacoustic (PA)/infrared (IR) thermal imaging, and high photothermal conversion efficiency (
March 2018
Renal-clearable quaternary chalcogenide nanocrystal for photoacoustic/magnetic resonance imaging guided tumor photothermal therapy
Publication date: March 2018
Source:Biomaterials, Volume 159 Author(s): Longfei Tan, Jing Wan, Weisheng Guo, Caizhang Ou, Tianlong Liu, Changhui Fu, Qiang Zhang, Xiangling Ren, Xing-Jie Liang, Jun Ren, Laifeng Li, Xianwei Meng Ultrasmall Cu2ZnSnS4 (CZTS) nanocrystals with high near infrared (NIR) photothermal conversion abilities and peroxidase-mimic properties are synthesized and functionalized with bovine serum albumin (BSA) for rapid clearance multifunctional theranostic platform. Due to the presence of Cu (I) of CZTS@BSA, H2O2 could be decomposed to produce highly reactive oxygen species (ROS), catalyzed by intrinsic peroxidase like activity of CZTS. The CZTS@BSA possesses high NIR absorption and excellent photoacoustic (PA) imaging abilities. The as-prepared CZTS@BSA is also reported as an efficient T1 contrast agent for inávivo MR imaging. Therefore, inávivo distribution and rapid renal clearance of CZTS@BSA are successfully tracked by PA/MR dual-modal-imaging and further proved by ICP-MS analysis. Systemic acute toxicity evaluation indicates CZTS@BSA have good biocompatibility to normal tissues and blood. All results reveal that CZTS@BSA could act as a rapid clearance theranostic nanoplatform for dual-modal-imaging guided tumor PTT.
March 2018
Injectable polypeptide hydrogel for dual-delivery of antigen and TLR3 agonist to modulate dendritic cells inávivo and enhance potent cytotoxic T-lymphocyte response against melanoma
Publication date: March 2018
Source:Biomaterials, Volume 159 Author(s): Huijuan Song, Pingsheng Huang, Jinfeng Niu, Gaona Shi, Chuangnian Zhang, Deling Kong, Weiwei Wang Transplantation of immune cells manipulated inávitro to dictate immune responses in the body is promising in cancer immunotherapy. However, this approach suffers from low cell survival after administration, insufficient cell homing to lymph nodes, and off-target. Here we demonstrate an injectable and self-assembled poly(l-valine) hydrogel as the delivery carrier of cargoes including antigen and immunopotentiator for DCs modulation. Our results indicate the vaccine formulation composed of tumor cell lysates (TCL), TLR3 agonist, poly(I:C) and polypeptide hydrogel can robustly recruit, activate and mature DCs inávitro and inávivo by sustained release of TCL and poly(I:C). Hydrogel as the delivery system significantly improves antigen persistence at the injection site and antigen drainage to lymph nodes. Strikingly, subcutaneous injection of hydrogel-based vaccine formulations in melanoma-bearing mice elicits good antitumor efficiency by evoking strong cytotoxic T-lymphocyte immune response. Hydrogel vaccine significantly promotes the production of CD8+ T cells in draining lymph nodes and tumor infiltrating T-lymphocytes. These findings suggest that inávivo program of DCs by injectable polypeptide hydrogel encapsulated with antigen and immunopentiator is able to direct immune responses against cancer. Our study also implies that such a hydrogel may serve as a multifunctional delivery platform of vaccines.
March 2018
Editorial Board
Publication date: March 2018
Source:Biomaterials, Volume 158

March 2018
VE-Cadherin regulates the self-renewal of mouse embryonic stem cells via LIF/Stat3 signaling pathway
Publication date: March 2018
Source:Biomaterials, Volume 158 Author(s): Ningning He, Xiaoniao Chen, Dan Wang, Ke Xu, Lingling Wu, Yuanyuan Liu, Hongyan Tao, Qinjun Zhao, Xiaocang Cao, Yuhao Li, Na Liu, Xin Qi, Zhongchao Han, Deling Kong, Jun Yang, Zongjin Li With the abilities of self-renewal and differentiation, embryonic stem (ES) cells provide an unlimited source for stem cell-based therapeutics. However, the maintenance of ES cells with mouse embryonic fibroblasts (MEFs) can limit the clinical translation of ES cells. In the present study, we synthesized a fusion protein of the immunoglobulin G (IgG) fragment crystallizable region and vascular endothelial cadherin (VE-cadherin) extracellular domain (VE-cad-Fc) as a substrate for mouse ES cell culture, and we hypothesized that VE-cadherin could enhance the pluripotency and self-renewal of ES cells. Furthermore, we introduced a Stat3 reporter imaging system into ES cells and investigated the mechanism of the pluripotency enhancement mediated by VE-cadherin through cultured ES cells on VE-cad-Fc-coated plates using molecular imaging techniques. The resulting data revealed that VE-cad-Fc could activate the Stat3 signaling pathway, leading to the upregulation of stemness-related markers SSEA-1 and alkaline phosphatase (ALP). Moreover, VE-cad-Fc recovered the expression of Oct4, c-Myc, Nanog, Sox2, Tbx3 and Klf4 in differentiated ES cells, as well as enhanced the pluripotency of ES cells. In conclusion, VE-cadherin fusion protein coating methods provide an alternative towards feeder free culture of ES cells, and the strategy developed in the present study may benefit the clinical translation of ES cell-based therapeutics.
March 2018
Noninvasive small-animal imaging of galectin-1 upregulation for predicting tumor resistance to radiotherapy
Publication date: March 2018
Source:Biomaterials, Volume 158 Author(s): Jianhao Lai, Dehua Lu, Chenran Zhang, Hua Zhu, Liquan Gao, Yanpu Wang, Rui Bao, Yang Zhao, Bing Jia, Fan Wang, Zhi Yang, Zhaofei Liu Increasing evidence indicates that the overexpression of galectin-1, a member of the galectin family, is related to tumor progression and invasion, as well as tumor resistance to therapies (e.g., radiotherapy). Herein, we investigated whether near-infrared fluorescence (NIRF) imaging and positron-emission tomography (PET) were sensitive approaches for detecting and quantitating galectin-1 upregulation inávivo. An anti-galectin-1 antibody was labeled with either an NIRF dye or 64Cu, and NIRF and PET imaging using the resulting probes (Dye-
March 2018
Amino-Si-rhodamines: A new class of two-photon fluorescent dyes with intrinsic targeting ability for lysosomes
Publication date: March 2018
Source:Biomaterials, Volume 158 Author(s): Hongxing Zhang, Jing Liu, Linfang Wang, Minjia Sun, Xiaohan Yan, Juanjuan Wang, Jian-Ping Guo, Wei Guo Noninvasive and specific visualization of lysosomes by fluorescence technology is critical for studying lysosomal trafficking in health and disease and for evaluating new cancer therapeutics that target tumor cell lysosomes. To date, there are two basic types of lysosomal probes whose lysosomal localization correlates with lysosomal acidity and endocytosis pathway, respectively. However, the former may suffer from pH-sensitive lysosomal localization and alkalization-induced lysosomal enzyme inactivation, and the latter need long incubation time to penetrate cell membrane due to the energy-dependency of endocytosis process. In this work, a new class of two-photon fluorescent dyes, termed amino-Si-rhodamines (ASiRs), were developed, which possess the intrinsic lysosome-targeted ability that is independent of lysosomal acidity and endocytosis pathway. As a result, ASiRs show not only the stable lysosomal localization against lysosomal pH changes and negligible interference to lysosomal function, but also excellent cell-membrane-permeability due to the energy-independent passive diffusion pathway. These merits, coupled with their excellent two-photon photophysical properties, long-term retention ability in lysosomes, and negligible cytotoxicity, make ASiRs very suitable for real-time and long-term tracking of lysosomes in living cells or tissues without interference to normal cellular processes. Moreover, the easy functionalization via amino linker further allows the construction of various fluorescent probes for biological targets of interest based on ASiR skeleton, as indicated by the cancer-targeted fluorescent probe ASiR6 as well as a fluorescent peroxynitrite probe ASiR-P.

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March 2018
Rattle-type Au@Cu2
March 2018
Precision design of nanomedicines to restore gemcitabine chemosensitivity for personalized pancreatic ductal adenocarcinoma treatment
Publication date: March 2018
Source:Biomaterials, Volume 158 Author(s): Xiao Zhao, Xiuchao Wang, Wei Sun, Keman Cheng, Hao Qin, Xuexiang Han, Yu Lin, Yongwei Wang, Jiayan Lang, Ruifang Zhao, Xiaowei Zheng, Ying Zhao, Jian shi, Jihui Hao, Qing Robert Miao, Guangjun Nie, He Ren Low chemosensitivity considerably restricts the therapeutic efficacy of gemcitabine (GEM) in pancreatic cancer treatment. Using immunohistochemical evaluation, we investigated that decreased expression of human equilibrative nucleoside transporter-1 (hENT1, which is the major GEM transporter across cell membranes) and increased expression of ribonucleotide reductase subunit 2 (RRM2, which decreases the cytotoxicity of GEM) was associated with low GEM chemosensitivity. To solve these problems, we employed a nanomedicine-based formulation of cationic liposomes for co-delivery of GEM along with siRNA targeting RRM2. Due to the specific endocytic uptake mechanism of nanocarriers and gene-silencing effect of RRM2 siRNA, this nanomedicine formulation significantly increased GEM chemosensitivity in tumor models of genetically engineered Panc1 cells with low hENT1 or high RRM2 expression. Moreover, in a series of patient-derived cancer cells, we demonstrated that the therapeutic benefits of the nanomedicine formulations were associated with the expression levels of hENT1 and RRM2. In summary, we found that the essential factors of GEM chemosensitivity were the expression levels of hENT1 and RRM2, and synthesized nanoformulations can overcome these problems. This unique design of nanomedicine not only provides a universal platform to enhance chemosensitivity but also contributes to the precision design and personalized treatment in nanomedicine.

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March 2018
Heterocellular 3D scaffolds as biomimetic to recapitulate the tumor microenvironment of peritoneal metastases inávitro and inávivo
Publication date: March 2018
Source:Biomaterials, Volume 158 Author(s): Emiel De Jaeghere, Elly De Vlieghere, Jasper Van Hoorick, Sandra Van Vlierberghe, Glenn Wagemans, Leen Pieters, Elodie Melsens, Marleen Praet, Jo Van Dorpe, Matthieu N. Boone, Rouba Ghobeira, Nathalie De Geyter, Marc Bracke, Christian Vanhove, Sara Neyt, Geert Berx, Bruno G. De Geest, Peter Dubruel, Heidi Declercq, Wim Ceelen, Olivier De Wever Peritoneal metastasis is a major cause of death and preclinical models are urgently needed to enhance therapeutic progress. This study reports on a hybrid hydrogel-polylactic acid (PLA) scaffold that mimics the architecture of peritoneal metastases at the qualitative, quantitative and spatial level. Porous PLA scaffolds with controllable pore size, geometry and surface properties are functionalized by type I collagen hydrogel. Co-seeding of cancer-associated fibroblasts (CAF) increases cancer cell adhesion, recovery and exponential growth by in situ heterocellular spheroid formation. Scaffold implantation into the peritoneum allows long-term follow-up (>14 weeks) and results in a time-dependent increase in vascularization, which correlates with cancer cell colonization inávivo. CAF, endothelial cells, macrophages and cancer cells show spatial and quantitative aspects as similarly observed in patient-derived peritoneal metastases. CAF provide long-term secretion of complementary paracrine factors implicated in spheroid formation inávitro as well as in recruitment and organization of host cells inávivo. In conclusion, the multifaceted heterocellular interactions that occur within peritoneal metastases are reproduced in this tissue-engineered implantable scaffold model.
March 2018
Stable gadolinium based nanoscale lyophilized injection for enhanced MR angiography with efficient renal clearance
Publication date: March 2018
Source:Biomaterials, Volume 158 Author(s): Kun Liu, Liang Dong, Yunjun Xu, Xu Yan, Fei Li, Yang Lu, Wei Tao, Huangyong Peng, Yadong Wu, Yang Su, Daishun Ling, Tao He, Haisheng Qian, Shu-Hong Yu There is a great demand to develop high-relaxivity nanoscale contrast agents for magnetic resonance (MR) angiography with high resolution. However, there should be more focus on stability, ion leakage and excretion pathway of the intravenously injected nanoparticles, which are closely related to their clinic potentials. Herein, uniform ultrasmall-sized NaGdF4 nanocrystal (sub-10
March 2018
Targeting death receptors for drug-resistant cancer therapy: Codelivery of pTRAIL and monensin using dual-targeting and stimuli-responsive self-assembling nanocomposites
Publication date: March 2018
Source:Biomaterials, Volume 158 Author(s): Fan Xu, Huihai Zhong, Ya Chang, Dongdong Li, Hongyue Jin, Meng Zhang, Huiyuan Wang, Chen Jiang, Youqing Shen, Yongzhuo Huang Chemoresistance remains a formidable hurdle against cancer therapy. Seeking for novel therapy strategies is an urgent need for those who no longer benefit from chemotherapy. Chemoresistance is usually associated with the dysfunction of intrinsic apoptosis. Targeting extrinsic apoptosis via TRAIL signaling and the death receptors could be a potential solution to treat chemoresistant cancer. A highly biocompatible nano system for codelivery of the TRAIL DNA and the death receptor sensitizer monensin was developed, in which low-molecular-weight PEI (LMW-PEI) was crosslinked by the sulfhydryl cyclodextrin via disulfide bonds, and then bound with DNA, thus forming the bioreducible polyplex cores. In addition, the cyclodextrin also functioned as a carrier for the hydrophobic monensin via host-guest inclusion. Poly-
March 2018
Targeting polysialic acid-abundant cancers using oncolytic adenoviruses with fibers fused to active bacteriophage borne endosialidase
Publication date: March 2018
Source:Biomaterials, Volume 158 Author(s): Nikolas T. Martin, Christoph Wrede, Julia Niemann, Jennifer Brooks, David Schwarzer, Florian K
March 2018
Editorial Board
Publication date: March 2018
Source:Biomaterials, Volume 157

March 2018
Influence of diabetes on the foreign body response to nitric oxide-releasing implants
Publication date: March 2018
Source:Biomaterials, Volume 157 Author(s): Robert J. Soto, Elizabeth P. Merricks, Dwight A. Bellinger, Timothy C. Nichols, Mark H. Schoenfisch The foreign body response (FBR) to nitric oxide (NO)-releasing subcutaneous implants was compared between healthy and streptozotocin-induced diabetic swine by evaluating inflammation, collagen capsule formation, and angiogenesis. Steel wire substrates were first modified with polyurethane membranes capable of diverse NO-release kinetics (NO fluxes and release durations of 0.8ľ630.0ápmolácm
March 2018
Magnesium alloy based interference screw developed for ACL reconstruction attenuates peri-tunnel bone loss in rabbits
Publication date: March 2018
Source:Biomaterials, Volume 157 Author(s): Jiali Wang, Yuanhao Wu, Huafang Li, Yang Liu, Xueling Bai, Wingho Chau, Yufeng Zheng, Ling Qin Peri-tunnel bone loss after anterior cruciate ligament (ACL) reconstruction is often observed clinically, which may detrimentally affect tendon graft integration with surrounding bone tissue. Biodegradable magnesium (Mg) based fixators in terms of interference screws may be suitable for fixation of the tendon graft due to their favorable effects on promotion of new bone formation. However, the poor mechanical strength of Mg is still one of the major challenges for its clinical applications. The addition of alloying elements into Mg is one of the strategies to improve their mechanical properties. Here, we prepared magnesium (Mg)-(4 and 6áwt%) zinc (Zn)-(0.2, 0.5, 1 and 2áwt%) strontium(Sr) alloys and tested their potential for attenuating peri-tunnel bone loss in ACL reconstruction. The optimal (6áwt%) Zn and (0.5áwt%) Sr contents were screened with respect to the microstructures, mechanical properties and corrosion behavior of these alloys. As compared to pure Mg, Mg-6Zn-0.5Sr rods and screws showed significantly higher torque and torsional stiffness in both numerical and experimental analysis. The inávitro cyto-compatibility of Mg-6Zn-0.5Sr alloy was assessed with MTT test and fluorescence assay. The Mg-6Zn-0.5Sr interference screw was designed for fixation of the tendon graft to the femoral tunnel in a rabbit model of ACL reconstruction, with a commercially available poly-lactide (PLA) screw for comparison. Inávivo high resolution peripheral quantitative computed tomography (HR-pQCT) scanning was performed to measure the degradation behavior of Mg-6Zn-0.5Sr interference screws and peri-tunnel bone quality at 0, 6, 12 and 16 weeks post-surgically. Mg-6Zn-0.5Sr interference screw was completely degraded within 12 weeks after surgery. The peri-tunnel bone loss was significantly attenuated in the Mg-6Zn-0.5Sr group when compared to the PLA group. Importantly, the bony ingrowth rapidly filled the cavity left by the complete degradation of Mg-6Zn-0.5Sr screws at 16 weeks. In histological analysis, more bone formation was observed in peri-tunnel region in the Mg-6Zn-0.5Sr group in comparison to the PLA group at 6 and 16 weeks after surgery. The femur-tendon graft-tibia complex was harvested at the end of week 6 and 16 post-operation for tensile testing. The maximum load to failure was significantly improved in the Mg-6Zn-0.5Sr group at week 16 post-operation. Therefore, our results indicate the potential clinical application of MgZnSr based interference screws in ACL reconstruction.
March 2018
Zwitterionic starch-based hydrogel for the expansion and ôstemnessö maintenance of brown adipose derived stem cells
Publication date: March 2018
Source:Biomaterials, Volume 157 Author(s): Dianyu Dong, Tong Hao, Changyong Wang, Ying Zhang, Zhihui Qin, Boguang Yang, Wancai Fang, Lei Ye, Fanglian Yao, Junjie Li Brown adipose derived stem cells (BADSCs) have become a promising stem cell treatment candidate for myocardial infarction because of their efficiently spontaneous differentiation capacity towards cardiomyocytes. The lack of existing cell passage protocols motivates us to develop a neotype 3D cell expansion technique for BADSCs. In this study, ôclickableö zwitterionic starch based hydrogels are developed using methacrylate modified sulfobetaine derived starch with dithiol-functionalized poly (ethylene glycol) as crosslinker via the ôthiol-eneö Michael addition reaction. Moreover, CGRGDS peptide is immobilized into the hydrogel via a similar ôclickableö approach. Their Young's moduli range from 22.28 to 74.81
March 2018
Biomimetic elastomeric, conductive and biodegradable polycitrate-based nanocomposites for guiding myogenic differentiation and skeletal muscle regeneration
Publication date: March 2018
Source:Biomaterials, Volume 157 Author(s): Yuzhang Du, Juan Ge, Yannan Li, Peter X. Ma, Bo Lei Artificial muscle-like biomaterials have gained tremendous interests owing to their broad applications in regenerative medicine, wearable devices, bioelectronics and artificial intelligence. Unfortunately, key challenges are still existed for current materials, including biomimetic viscoelasticity, biocompatibility and biodegradation, multifunctionality. Herein, for the first time, we develop highly elastomeric, conductive and biodegradable poly (citric acid-octanediol-polyethylene glycol)(PCE)-graphene (PCEG) nanocomposites, and demonstrate their applications in myogenic differentiation and guiding skeletal muscle tissue regeneration. In PCEG nanocomposites, PCE provides the biomimetic elastomeric behavior, and the addition of reduced graphene oxide (RGO) endows the enhanced mechanical strength and conductivity. The highly elastomeric behavior, significantly enhanced modulus (400%ľ800%), strength (200%ľ300%) of PCEG nanocomposites with controlled biodegradability and electrochemical conductivity were achieved. The myoblasts proliferation and myogenic differentiation were significantly improved by PCEG nanocomposite. Significantly high inávivo biocompatibility of PCEG nanocomposites was observed when implanted in the subcutaneous tissue for 4 weeks in rats. PCEG nanocomposites could significantly enhance the muscle fibers and blood vessels formation inávivo in a skeletal muscle lesion model of rat. This study may provide a novel strategy to develop multifunctional elastomeric nanocomposites with high biocompatibility for potential soft tissue regeneration and stretchable bioelectronic devices.
March 2018
Magnesium phosphate ceramics incorporating a novel indene compound promote osteoblast differentiation inávitro and bone regeneration inávivo
Publication date: March 2018
Source:Biomaterials, Volume 157 Author(s): Ju Ang Kim, Hui-suk Yun, Young-Ae Choi, Jung-Eun Kim, So-Young Choi, Tae-Geon Kwon, Young Kyung Kim, Tae-Yub Kwon, Myung Ae Bae, Nak Jeong Kim, Yong Chul Bae, Hong-In Shin, Eui Kyun Park Incorporating bioactive molecules into synthetic ceramic scaffolds is challenging. In this study, to enhance bone regeneration, a magnesium phosphate (MgP) ceramic scaffold was incorporated with a novel indene compound, KR-34893. KR-34893 induced the deposition of minerals and expression of osteoblast marker genes in primary human bone marrow mesenchymal stem cells (BMSCs) and a mouse osteoblastic MC3T3-E1 cell line. Analysis of the mode of action showed that KR-34893 induced the phosphorylation of MAPK/extracellular signal-regulated kinase and extracellular signal-regulated kinase, and subsequently the expression of bone morphogenetic protein 7, accompanied by SMAD1/5/8 phosphorylation. Accordingly, KR-34893 was incorporated into an MgP scaffold prepared by 3D printing at room temperature, followed by cement reaction. KR-34893-incorporated MgP (KR-MgP) induced the expression of osteoblast differentiation marker genes inávitro. In a rat calvaria defect model, KR-MgP scaffolds enhanced bone regeneration and increased bone volume compared with MgP scaffolds, as assessed by micro-computed tomography and histological analyses. In conclusion, we developed a method for producing osteoinductive MgP scaffolds incorporating a bioactive organic compound, without high temperature sintering. The KR-MgP scaffolds enhanced osteoblast activation inávitro and bone regeneration inávivo.
March 2018
A decade of progress in liver regenerative medicine
Publication date: March 2018
Source:Biomaterials, Volume 157 Author(s): Jingwei Zhang, Xin Zhao, Liguo Liang, Jun Li, Utkan Demirci, ShuQi Wang Liver diseases can be caused by viral infection, metabolic disorder, alcohol consumption, carcinoma or injury, chronically progressing to end-stage liver disease or rapidly resulting in acute liver failure. In either situation, liver transplantation is most often sought for life saving, which is, however, significantly limited by severe shortage of organ donors. Until now, tremendous multi-disciplinary efforts have been dedicated to liver regenerative medicine, aiming at providing transplantable cells, microtissues, or bioengineered whole liver via tissue engineering, or maintaining partial liver functions via extracorporeal support. In both directions, new compatible biomaterials, stem cell sources, and bioengineering approaches have fast-forwarded liver regenerative medicine towards potential clinical applications. Another important progress in this field is the development of liver-on-a-chip technologies, which enable tissue engineering, disease modeling, and drug testing under biomimetic extracellular conditions. In this review, we aim to highlight the last decade's progress in liver regenerative medicine from liver tissue engineering, bioartificial liver devices (BAL), to liver-on-a-chip platforms, and then to present challenges ahead for further advancement.
March 2018
Strontium and bisphosphonate coated iron foam scaffolds for osteoporotic fracture defect healing
Publication date: March 2018
Source:Biomaterials, Volume 157 Author(s): Seemun Ray, Ulrich Thormann, Marlen Eichelroth, Matth
March 2018
Regeneration of cortical tissue from brain injury by implantation of defined molecular gradient of semaphorin 3A
Publication date: March 2018
Source:Biomaterials, Volume 157 Author(s): Zhen Xu, Wei Wang, Yutian Ren, Wenchong Zhang, Peilin Fang, Linfeng Huang, Xin Wang, Peng Shi Despite great efforts in the exploration of therapeutic strategies for treating brain injuries, it is still challenging to regenerate neural tissues and to restore the lost function within an injured brain. In this report, we employed a tissue engineering approach to regenerate cortical tissue from brain injury by implantation of defined semaphorin 3A (Sema3A) gradient packaged in a hydrogel based device. Over a thirty-day recovery period, the implanted Sema3A gradient was sufficient to induce substantial migration of neural progenitor cells to the hydrogel and to promote differentiation of these cells for neuroregeneration at the injury site. As revealed by molecular characterization and RNA transcriptome analysis, the regenerated tissues induced by Sema3A gradient exhibited significant similarity to normal cortical tissues. Many genes associated with neuronal migration and stem cell differentiation were significantly up-regulated. In addition, our result suggested a crosstalk between Sema3A and Wnt/
March 2018
Optical molecular imaging for tumor detection and image-guided surgery
Publication date: March 2018
Source:Biomaterials, Volume 157 Author(s): Chensu Wang, Zhaohui Wang, Tian Zhao, Yang Li, Gang Huang, Baran D. Sumer, Jinming Gao We have witnessed rapid development of fluorescence molecular imaging of solid tumors for cancer diagnosis and image-guided surgery in the past decade. Many biomarkers unique to cancer cells or tumor microenvironment, such as cell surface receptors, hypoxia, secreted proteases and extracellular acidosis have been characterized, and can be used to distinguish cancer from normal tissue. A variety of optical imaging probes have been developed to target these biomarkers to improve tumor contrast over the background tissue. Unlike conventional anatomical and molecular imaging technologies, fluorescent imaging method benefits from its safety, high-spatial resolution and real-time capability, and therefore, has become a highly adoptable imaging method for tumor detection and image-guided surgery in clinics. In this review, we summarize recent progress in Ĺalways-ONĺ and stimuli-activatable fluorescent imaging probes, and discuss their potentials in tumor detection and image-guided surgery.

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March 2018
Self-assembly regulated anticancer activity of platinum coordinated selenomethionine
Publication date: March 2018
Source:Biomaterials, Volume 157 Author(s): Tianyu Li, Wentian Xiang, Feng Li, Huaping Xu It is urgently desired that self-assembly methods can be used to develop smart nanomedicines with adjustable anticancer activity and concise structure. Herein, we design carrier-free small molecule assemblies of platinum coordinated selenomethionine, which exhibit adjustable anticancer activity regulated by their self-assembly behaviors. The small molecule assemblies are prepared by coordination of selenomethionine esters with cisplatin. Their self-assembly behaviors can be tuned by esterification between selenomethionine and alcohols with different alkyl lengths, which results in adjustable anticancer activities. The coordination assemblies exhibit high anticancer activity as well as low side effects. Mechanistic studies indicate that they can consume glutathione (GSH) and therefore induce high level of reactive oxygen species (ROS) in cancer cells, which further lead to cell apoptosis. Our findings provide new strategies and insights in developing small molecule assemblies for cancer treatment.

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March 2018
Genomic form of rhodopsin DNA nanoparticles rescued autosomal dominant Retinitis pigmentosa in the P23H knock-in mouse model
Publication date: March 2018
Source:Biomaterials, Volume 157 Author(s): Rajendra Narayan Mitra, Min Zheng, Ellen R. Weiss, Zongchao Han Retinitis pigmentosa (RP) is a group of inherited retinal degenerative conditions and a leading cause of irreversible blindness. 25%ľ30% of RP cases are caused by inherited autosomal dominant (ad) mutations in the rhodopsin (Rho) protein of the retina, which impose a barrier for developing therapeutic treatments for this genetically heterogeneous disorder, as simple gene replacement is not sufficient to overcome dominant disease alleles. Previously, we have explored using the genomic short-form of Rho (sgRho) for gene augmentation therapy of RP in a Rho knockout mouse model. We have shown improved gene expression and fewer epigenetic modifications compared with the use of a Rho cDNA expression construct. In the current study, we altered our strategy by delivering a codon-optimized genomic form of Rho (co-sgRho) (for gene replacement) in combination with an RNAi-based inactivation of endogenous Rho alleles (gene suppression of both mutant Rho alleles, but mismatched with the co-sgRho) into a homozygous Rho P23H/P23H knock-in (KI) RP mouse model, which has a severe phenotype of adRP. In addition, we have conjugated a cell penetrating TAT peptide sequence to our previously established CK30PEG10 diblock co-polymer. The DNAs were compacted with CK30PEG10-TAT diblock co-polymer to form DNA nanoparticles (NPs). These NPs were injected into the sub-retinal space of the KI mouse eyes. As a proof of concept, we demonstrated the efficiency of this strategy in the partial improvement of visual function in the Rho P23H/P23H KI mouse model.

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March 2018
DNA nanoparticles for ophthalmic drug delivery
Publication date: March 2018
Source:Biomaterials, Volume 157 Author(s): Jan Willem de Vries, Sven Schnichels, Jos
March 2018
Tumor acidity activating multifunctional nanoplatform for NIR-mediated multiple enhanced photodynamic and photothermal tumor therapy
Publication date: March 2018
Source:Biomaterials, Volume 157 Author(s): Junjie Liu, Huining Liang, Menghuan Li, Zhong Luo, Jixi Zhang, Xingming Guo, Kaiyong Cai The study reports a multifunctional nanoplatform based on mesoporous silica coated gold nanorod (AuNR@MSN) to overcome biological barriers associating with nanocarrier for multiple enhanced photodynamic therapy (PDT) and photothermal therapy (PPT). Indocyanine green (ICG) was loaded into AuNR@MSN and end-capped with
February 2018
Multifunctional hybrid micelles with tunable active targeting and acid/phosphatase-stimulated drug release for enhanced tumor suppression
Publication date: March 2018
Source:Biomaterials, Volume 157 Author(s): Xuhan Liu, Yinghuan Li, Xi Tan, Rong Rao, Yuanyuan Ren, Lingyan Liu, Xiangliang Yang, Wei Liu Therapeutic efficacy of conventional single PEGylated polymeric micelles is significantly reduced by limited endocytosis and intracellular drug release. To improve drug delivery efficiency, poly (ethylene glycol)-block-poly (l-lactic acid)/(Arg-Gly-Asp-Phe)-poly (aminoethyl ethylene phosphate)-block-poly (l-lactic acid) (PEG-PLLA/RGDF-PAEEP-PLLA) hybrid micelles with tunable active targeting and acid/phosphatase-stimulated drug release are developed. The optimized hybrid micelles with 6áwt % of RGDF have favorable inávitro and inávivo activities. The hybrid micelles could temporarily shield the targeting efficacy of RGDF at pH 7.4 due to the steric effect exerted by concealment of RGDF peptides in the PEG corona, which strongly decreases the clearance by mononuclear phagocyte system and consequently improves the tumor accumulation. Inside the solid tumor with a lower acidic pH, the hybrid micelles restore the active tumor targeting property with exposed RGDF on the surface of the micelles because of the increased protonation and stretching degree of PAEEP blocks. RGDF-mediated endocytosis improves the tumor cell uptake. The hybrid micelles would also enhance intracellular drug release because of the hydrolysis of the acid/phosphatase-sensitivity of PAEEP blocks in endo/lysosome. Systemic administration of the hybrid micelles significantly inhibits tumor growth by 96% due to the integration of enhanced circulation time, tumor accumulation, cell uptake and intracellular drug release.
February 2018
Editorial Board
Publication date: February 2018
Source:Biomaterials, Volume 156

February 2018
Structure-based design for binding peptides in anti-cancer therapy
Publication date: February 2018
Source:Biomaterials, Volume 156 Author(s): Sheng-Hung Wang, John Yu The conventional anticancer therapeutics usually lack cancer specificity, leading to damage of normal tissues that patients find hard to tolerate. Ideally, anticancer therapeutics carrying payloads of drugs equipped with cancer targeting peptides can act like ôguided missilesö with the capacity of targeted delivery toward many types of cancers. Peptides are amenable for conjugation to nano drugs for functionalization, thereby improving drug delivery and cellular uptake in cancer-targeting therapies. Peptide drugs are often more difficult to design through molecular docking and in silico analysis than small molecules, because peptide structures are more flexible, possess intricate molecular conformations, and undergo complex interactions. In this review, the development and application of strategies for structure-based design of cancer-targeting peptides against GRP78 are discussed. This Review also covers topics related to peptide pharmacokinetics and targeting delivery, including molecular docking studies, features that provide advantages for inávivo use, and properties that influence the cancer-targeting ability. Some advanced technologies and special peptides that can overcome the pharmacokinetic challenges have also been included.

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February 2018
Rerouting mesenchymal stem cell trajectory towards epithelial lineage by engineering cellular niche
Publication date: February 2018
Source:Biomaterials, Volume 156 Author(s): Ananya Barui, Farhan Chowdhury, Abhay Pandit, Pallab Datta Mesenchymal stromal/stem cells (MSCs) are multipotent cells that offer a promising outcome in the field of regenerative medicine. MSCs are present in various tissues including bone marrow, fat, skin, and placenta. The interest in clinical application of these mesoderm-derived MSCs is primarily fueled by their high self-renewal capacity and multipotency. Although, early studies indicated limited differentiation capacity of MSCs into same cell lineages from which they were isolated, subsequent investigations showed differentiation potential into other cell types of mesoderm origin including osteoblasts, adipocytes, fibroblasts, cardiomyocytes, and chondrocytes. Furthermore, MSCs exhibit a remarkable feature of transdifferentiation into ectodermal, neuroectodermal, and endodermal cells, phenomena referred to as Ĺstem cell plasticityĺ. This opened the possibility of clinical applications of MSCs in the regeneration of other tissues like corneal reconstruction, treatment of acute lung injury, oral mucosal regeneration, homing of MSCs for regeneration at sites of injury etc. Though several evidence have accrued demonstrating this phenomenon, there is still a gap in understanding the molecular mechanism of such transitions which will be important to efficiently control the process. Interestingly, the process can be drawn a parallel with the Mesenchymal to Epithelial Transitions (MET) that takes place inside the body during embryonic development or certain pathophysiological conditions. In this review, a brief attempt is first made to understand the evidence of MSC transdifferentiation based on the current knowledge about MET. We then specifically focus on systematic presentation and analysis of the microenvironment factors involved in MSC transdifferentiation to epithelial lineages which would have applications in regenerative medicine.
February 2018
Does soft really matter? Differentiation of induced pluripotent stem cells into mesenchymal stromal cells is not influenced by soft hydrogels
Publication date: February 2018
Source:Biomaterials, Volume 156 Author(s): Roman Goetzke, Julia Franzen, Alina Ostrowska, Michael Vogt, Andreas Blaeser, Gerd Klein, Bj
February 2018
Biomaterials-based 3D cell printing for next-generation therapeutics and diagnostics
Publication date: February 2018
Source:Biomaterials, Volume 156 Author(s): Jinah Jang, Ju Young Park, Ge Gao, Dong-Woo Cho Building human tissues via 3D cell printing technology has received particular attention due to its process flexibility and versatility. This technology enables the recapitulation of unique features of human tissues and the all-in-one manufacturing process through the design of smart and advanced biomaterials and proper polymerization techniques. For the optimal engineering of tissues, a higher-order assembly of physiological components, including cells, biomaterials, and biomolecules, should meet the critical requirements for tissue morphogenesis and vascularization. The convergence of 3D cell printing with a microfluidic approach has led to a significant leap in the vascularization of engineering tissues. In addition, recent cutting-edge technology in stem cells and genetic engineering can potentially be adapted to the 3D tissue fabrication technique, and it has great potential to shift the paradigm of disease modeling and the study of unknown disease mechanisms required for precision medicine. This review gives an overview of recent developments in 3D cell printing and bioinks and provides technical requirements for engineering human tissues. Finally, we propose suggestions on the development of next-generation therapeutics and diagnostics.
February 2018
Emergence of synthetic mRNA: Inávitro synthesis of mRNA and its applications in regenerative medicine
Publication date: February 2018
Source:Biomaterials, Volume 156 Author(s): Hyokyoung Kwon, Minjeong Kim, Yunmi Seo, Yae Seul Moon, Hwa Jeong Lee, Kyuri Lee, Hyukjin Lee The field of gene therapy has evolved over the past two decades after the first introduction of nucleic acid drugs, such as plasmid DNA (pDNA). With the development of inávitro transcription (IVT) methods, synthetic mRNA has become an emerging class of gene therapy. IVT mRNA has several advantages over conventional pDNA for the expression of target proteins. mRNA does not require nuclear localization to mediate protein translation. The intracellular process for protein expression is much simpler and there is no potential risk of insertion mutagenesis. Having these advantages, the level of protein expression is far enhanced as comparable to that of viral expression systems. This makes IVT mRNA a powerful alternative gene expression system for various applications in regenerative medicine. In this review, we highlight the synthesis and preparation of IVT mRNA and its therapeutic applications. The article includes the design and preparation of IVT mRNA, chemical modification of IVT mRNA, and therapeutic applications of IVT mRNA in cellular reprogramming, stem cell engineering, and protein replacement therapy. Finally, future perspectives and challenges of IVT mRNA are discussed.
February 2018
MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity
Publication date: February 2018
Source:Biomaterials, Volume 156 Author(s): Shipin Zhang, Shang Jiunn Chuah, Ruenn Chai Lai, James Hoi Po Hui, Sai Kiang Lim, Wei Seong Toh Mesenchymal stem cell (MSC) exosome was previously shown to be effective in repairing critical size osteochondral defects in an immunocompetent rat model. Here we investigate the cellular processes modulated by MSC exosomes and the mechanism of action underlying the exosome-mediated responses in cartilage repair. We observed that exosome-mediated repair of osteochondral defects was characterised by increased cellular proliferation and infiltration, enhanced matrix synthesis and a regenerative immune phenotype. Using chondrocyte cultures, we could attribute the rapid cellular proliferation and infiltration during exosome-mediated cartilage repair to exosomal CD73-mediated adenosine activation of AKT and ERK signalling. Inhibitors of AKT or ERK phosphorylation suppressed exosome-mediated increase in cell proliferation and migration but not matrix synthesis. The role of exosomal CD73 was confirmed by the attenuation of AKT and ERK signalling by AMPCP, a CD73 inhibitor and theophylline, an adenosine receptor antagonist. Exosome-treated defects also displayed a regenerative immune phenotype characterised by a higher infiltration of CD163+ regenerative M2 macrophages over CD86+ M1 macrophages, with a concomitant reduction in pro-inflammatory synovial cytokines IL-1
February 2018
Crosstalk between developing vasculature and optogenetically engineered skeletal muscle improves muscle contraction and angiogenesis
Publication date: February 2018
Source:Biomaterials, Volume 156 Author(s): Tatsuya Osaki, Vivek Sivathanu, Roger D. Kamm Capillary networks surrounding skeletal muscle play an important role in not only supplying oxygen and nutrients but also in regulating the myogenesis and repair of skeletal muscle tissues. Herein, we model the early stages of 3D vascularized muscle fiber formation inávitro using a sequential molding technique to investigate interactions between angiogenesis of endothelial cells and myogenesis of skeletal muscle cells. Channelrhodopsin-2 C2C12 muscle fiber bundles and 3D vascular structures (600á
February 2018
Soft chitosan microbeads scaffold for 3D functional neuronal networks
Publication date: February 2018
Source:Biomaterials, Volume 156 Author(s): Maria Teresa Tedesco, Donatella Di Lisa, Paolo Massobrio, Nicol
February 2018
Microenvironments to study migration and somal translocation in cortical neurons
Publication date: February 2018
Source:Biomaterials, Volume 156 Author(s): Shifang Zhao, Wenqiang Fan, Xiang Guo, Longjian Xue, Benedikt Berninger, Marcelo J. Salierno, Ar
February 2018
Cold atmospheric plasma (CAP), a novel physicochemical source, induces neural differentiation through cross-talk between the specific RONS cascade and Trk/Ras/ERK signaling pathway
Publication date: February 2018
Source:Biomaterials, Volume 156 Author(s): Ja-Young Jang, Young June Hong, Junsup Lim, Jin Sung Choi, Eun Ha Choi, Seongman Kang, Hyangshuk Rhim Plasma, formed by ionization of gas molecules or atoms, is the most abundant form of matter and consists of highly reactive physicochemical species. In the physics and chemistry fields, plasma has been extensively studied; however, the exact action mechanisms of plasma on biological systems, including cells and humans, are not well known. Recent evidence suggests that cold atmospheric plasma (CAP), which refers to plasma used in the biomedical field, may regulate diverse cellular processes, including neural differentiation. However, the mechanism by which these physicochemical signals, elicited by reactive oxygen and nitrogen species (RONS), are transmitted to biological system remains elusive. In this study, we elucidated the physicochemical and biological (PCB) connection between the CAP cascade and Trk/Ras/ERK signaling pathway, which resulted in neural differentiation. Excited atomic oxygen in the plasma phase led to the formation of RONS in the PCB network, which then interacted with reactive atoms in the extracellular liquid phase to form nitric oxide (NO). Production of large amounts of superoxide radical (O2
February 2018
One-pot synthesis of pH-responsive charge-switchable PEGylated nanoscale coordination polymers for improved cancer therapy
Publication date: February 2018
Source:Biomaterials, Volume 156 Author(s): Yu Yang, Ligeng Xu, Wenjun Zhu, Liangzhu Feng, Jingjing Liu, Qian Chen, Ziliang Dong, Jiayue Zhao, Zhuang Liu, Meiwan Chen Nanoscale coordination polymers (NCPs) are promising nanomedicine platforms featured with biodegradability and versatile functionalities. However, multi-step post-synthesis surface modification is usually required to functionalize as-made NCPs before their biomedical applications. Moreover, efforts are still required to design therapeutic NCPs responsive to the unique tumor microenvironment to achieve more specific and effective therapy. Herein, we uncover a simple yet general strategy to synthesize a series of polyethylene glycol (PEG) modified NCPs via a one-step method by adding poly-histidine-PEG co-polymer into the mixture of metal ions and organic ligands during NCPs formation. With NCPs consisting Ca2+/dicarboxylic cisplatin (IV) prodrug as the example, we show that such Ca/Pt(IV)@pHis-PEG NCPs are highly sensitive to pH changes. With slightly negative charges and compact structure under pH 7.4 during blood circulation, those NCPs exhibit efficient passive accumulation in the tumor, in which the reduced pH (c.a. 6.5) would trigger charge conversion and size expansion to enhance their tumor retention and cell internationalization. After cellular uptake, NCPs within cell endo-/lysosomes with further reduced pH would then lead to decomposition of those NCPs and thus drug release. Chemotherapy with Ca/Pt(IV)@pHis-PEG NCPs in our animal tumor model demonstrates great efficacy under low drug doses, and is found to be particularly effective towards solid tumors with reduced pH.

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February 2018
Co-delivery of human cancer-testis antigens with adjuvant in protein nanoparticles induces higher cell-mediated immune responses
Publication date: February 2018
Source:Biomaterials, Volume 156 Author(s): Medea Neek, Jo Anne Tucker, Tae Il Kim, Nicholas M. Molino, Edward L. Nelson, Szu-Wen Wang Nanoparticles have attracted considerable interest as cancer vaccine delivery vehicles for inducing sufficient CD8+ T cell-mediated immune responses to overcome the low immunogenicity of the tumor microenvironment. Our studies described here are the first to examine the effects of clinically-tested human cancer-testis (CT) peptide epitopes within a synthetic nanoparticle. Specifically, we focused on two significant clinical CT targets, the HLA-A2 restricted epitopes of NY-ESO-1 and MAGE-A3, using a viral-mimetic packaging strategy. Our data shows that simultaneous delivery of a NY-ESO-1 epitope (SLLMWITQV) and CpG using the E2 subunit assembly of pyruvate dehydrogenase (E2 nanoparticle), resulted in a 25-fold increase in specific IFN-
February 2018
A gapmer aptamer nanobiosensor for real-time monitoring of transcription and translation in single cells
Publication date: February 2018
Source:Biomaterials, Volume 156 Author(s): Shue Wang, Yuan Xiao, Donna D. Zhang, Pak Kin Wong Transcription and translation are under tight spatiotemporal regulation among cells to coordinate multicellular organization. Methods that allow massively parallel detection of gene expression dynamics at the single cell level are required for elucidating the complex regulatory mechanisms. Here we present a multiplex nanobiosensor for real-time monitoring of protein and mRNA expression dynamics in live cells based on gapmer aptamers and complementary locked nucleic acid probes. Using the multiplex nanobiosensor, we quantified spatiotemporal dynamics of vascular endothelial growth factor A mRNA and protein expressions in single human endothelial cells during microvascular self-organization. Our results revealed distinct gene regulatory processes in the heterogeneous cell subpopulations.
February 2018
A mitochondrial-targeting near-infrared fluorescent probe for bioimaging and evaluating endogenous superoxide anion changes during ischemia/reperfusion injury
Publication date: February 2018
Source:Biomaterials, Volume 156 Author(s): Xiaoyue Han, Rui Wang, Xinyu Song, Fabiao Yu, Changjun Lv, Lingxin Chen The outburst of superoxide anion (O2

Overcoming obstacles in the tumor microenvironment: Recent advancements in nanoparticle delivery for cancer theranostics
Publication date: February 2018
Source:Biomaterials, Volume 156 Author(s): Marta Overchuk, Gang Zheng Despite rapid advancements in the field of nanotechnology, there is mounting frustration in the scientific community regarding the translational impact of nanomedicine. Modest therapeutic performance of FDA-approved nanomedicines combined with multiple disappointing clinical trials (such as phase III HEAT trial) have raised questions about the future of nanomedicine. Encouraging breakthroughs, however, have been made in the last few years towards the development of new classes of nanoparticles that can respond to tumor microenvironmental conditions and successfully deliver therapeutic agents to cancer cells. Concurrently, a great deal of effort has also been devoted to alter various parameters of tumor pathophysiology to pre-treat tumors before nanoparticles are administered. Such Ĺprimingĺ treatments improve access of the systemically administered agents to the tumor and promote drug penetration into the deeper layers of tumor tissue. This review will highlight recent advances in cancer nanomedicine exploiting both nanoparticle design and tumor microenvironment modification; and provide a critical perspective on the future development of nanomedicine delivery in oncology.

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