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Ganesh C Ingavle, Marissa Gionet-Gonzales, Charlotte E Vorwald, Laurie K Bohannon, Kaitlin Clark, Larry D Galuppo, J Kent Leach
The efficacy of cell-based therapies as an alternative to autologous bone grafts requires biomaterials to localize cells at the defect and drive osteogenic differentiation. Hydrogels are ideal cell delivery vehicles that can provide instructional cues via their composition or mechanical properties but commonly lack osteoconductive components that nucleate mineral. To address this challenge, we entrapped mesenchymal stromal cells (MSCs) in a composite hydrogel based on two naturally-derived polymers (alginate and hyaluronate) containing biomineralized polymeric microspheres...
January 10, 2019: Biomaterials
Biji Mathew, Sriram Ravindran, Xiaorong Liu, Leianne Torres, Mohansrinivas Chennakesavalu, Chun-Chieh Huang, Liang Feng, Ruth Zelka, Jasmine Lopez, Monica Sharma, Steven Roth
Retinal ischemia is a major cause of vision loss and impairment and a common underlying mechanism associated with diseases such as glaucoma, diabetic retinopathy, and central retinal artery occlusion. The regenerative capacity of the diseased human retina is limited. Our previous studies have shown the neuroprotective effects of intravitreal injection of mesenchymal stem cells (MSC) and MSC-conditioned medium in retinal ischemia in rats. Based upon the hypothesis that the neuroprotective effects of MSCs and conditioned medium are largely mediated by extracellular vesicles (EVs), MSC derived EVs were tested in an in-vitro oxygen-glucose deprivation (OGD) model of retinal ischemia...
January 9, 2019: Biomaterials
Ming-Yin Shen, Te-I Liu, Ting-Wei Yu, Reesha Kv, Wen-Hsuan Chiang, Yuan-Chung Tsai, Hsin-Hung Chen, Sung-Chyr Lin, Hsin-Cheng Chiu
Although oral formulations of anticancer chemotherapies are clinically available, the therapeutic action relies mostly on drug absorption, being inevitably accompanied with systemic side effects. It is thus desirable to develop oral therapy systems for the local treatment of colon cancers featured with highly selective delivery to cancer cells and minimized systemic drug absorption. The present study demonstrates the effective accumulation and cell uptake of the doxorubicin and superparamagnetic iron oxide nanoparticles-loaded solid lipid nanoparticle (SLN) delivery system for chemo/magnetothermal combination therapy at tumors by hierarchical targeting of folate (FA) and dextran coated on SLN surfaces in a sequential layer-by-layer manner...
January 9, 2019: Biomaterials
Jung-Hwan Lee, Dong-Hwee Kim, Hae-Hyoung Lee, Hae-Won Kim
Tissue engineers use biomaterials or apply forces to alter cell behaviors and cure damaged/diseased tissues. The external physical cues perceived by cells are transduced intracellularly along the mechanosensitive machineries, including subcellular adhesion molecules and cytoskeletons. The signals are further channeled to a nucleus through the physical links of nucleoskeleton and cytoskeleton or the biochemical translocation of transcription factors. Thus, the external cues are thought to affect directly or indirectly the nucleus and the genetic transcriptional process, ultimately determining cell fate...
January 8, 2019: Biomaterials
Colin D Paul, Alex Hruska, Jack R Staunton, Hannah A Burr, Kathryn M Daly, Jiyun Kim, Nancy Jiang, Kandice Tanner
Biophysical aspects of in vivo tissue microenvironments include microscale mechanical properties, fibrillar alignment, and architecture or topography of the extracellular matrix (ECM). These aspects act in concert with chemical signals from a myriad of diverse ECM proteins to provide cues that drive cellular responses. Here, we used a bottom-up approach to build fibrillar architecture into 3D amorphous hydrogels using magnetic-field driven assembly of paramagnetic colloidal particles functionalized with three types of human ECM proteins found in vivo...
January 8, 2019: Biomaterials
Heejun Shin, Kun Na
Anticancer immunotherapy is emerging as a promising tumor treatment that can replace the conventional tumor treatment such as surgery, radiation and chemo drug, but its therapeutic effect against solid tumor is limited due to the tumor microenvironment (TME). Herein, to overcome this limitation, the biocompatibility controllable immuno-sensitizer (BCI) based on polyethylene imine that can be applied to solid tumors is developed. BCI accumulates in the tumors by EPR effect and induces in situ tumor destruction that convert tumors into antigen source by biocompatibility change through surface charge switching in response to the acidic TME...
January 7, 2019: Biomaterials
Xing Li, Dingyang Liu, Zhifeng Xiao, Yannan Zhao, Sufang Han, Bing Chen, Jianwu Dai
Complete transected spinal cord injury (SCI) severely influences the quality of life and mortality rates of animals and patients. In the past decade, many simple and combinatorial therapeutic treatments have been tested in improving locomotor function in animals with this extraordinarily challenging SCI. The potential mechanism for promotion of locomotor function relies either on direct motor axon regeneration through the lesion gap or indirect neuronal relay bridging to functionally reconnect transected spinal stumps...
January 7, 2019: Biomaterials
Solji Lee, Daewon Han, Hyun-Goo Kang, Su Jin Jeong, Jae-Eun Jo, Jongdae Shin, Do Kyung Kim, Hwan-Woo Park
Obesity and overweight, the most serious health problems, are associated with chronic metabolic complications such as type 2 diabetes, insulin resistance, and nonalcoholic fatty liver disease (NAFLD). However, current pharmacological therapies for obesity are challenged by potential side effects, low effectiveness, and low aqueous solubility, which limit their clinical application. Here, we develop nifedipine-loaded nanoparticles (NFD-NPs) that alleviate obesity-related metabolic dysfunction to be used as instruments for translational medicine...
January 7, 2019: Biomaterials
V H Giang Phan, Huu Thuy Trang Duong, Thavasyappan Thambi, Thanh Loc Nguyen, Md Hasan Turabee, Yue Yin, Seong Han Kim, Jaeyun Kim, Ji Hoon Jeong, Doo Sung Lee
Lymphoid organs, which are populated by dendritic cells (DCs), are highly specialized tissues and provide an ideal microenvironment for T-cell priming. However, intramuscular or subcutaneous delivery of vaccine to DCs, a subset of antigen-presenting cells, has failed to stimulate optimal immune response for effective vaccination and need for adjuvants to induce immune response. To address this issue, we developed an in situ-forming injectable hybrid hydrogel that spontaneously assemble into microporous network upon subcutaneous administration, which provide a cellular niche to host immune cells, including DCs...
January 6, 2019: Biomaterials
Jun Zhou, Chencheng Xue, Yanhua Hou, Menghuan Li, Yan Hu, Qiufang Chen, Yanan Li, Ke Li, Guanbin Song, Kaiyong Cai, Zhong Luo
Hypoxia plays vital roles in the development of tumor resistance against typical anticancer therapies and local reoxygenation has proved effective to overcome the hypoxia-induced chemoresistance. Perfluorocarbon (PFC) is an FDA approved oxygen carrier and currently vigorously investigated for oxygen delivery to tumors. This study reports a perfluorocarbon and etoposide (EP) loaded porous hollow Fe3 O4 -based theranostic nanoplatform capable of delivering oxygen to solid tumors to enhance their susceptibility against EP...
January 4, 2019: Biomaterials
JongHoon Ha, DaeYong Lee, Soo-Hwan Lee, Chae-Ok Yun, Yeu-Chun Kim
Mitochondria are the primary organelle of regulating apoptosis, and intracellular calcium ions are a key component of pro-apoptosis induction. Herein, we report an artificial apoptosis-inducing polypeptide that destabilizes the mitochondrial membrane and transports calcium ions into the cytosol, thereby synergistically creating severe oxidative conditions. The oxidative stress highly activates an apoptotic signaling cascade, and also inhibits cell migration and invasion in vitro and in vivo. The suggested strategy for simultaneous mitochondrial disruption and perturbed calcium homeostasis demonstrates the applicability of polypeptide-based therapeutics as potent apoptosis-inducers in cancer therapy...
January 4, 2019: Biomaterials
Zhenqi Jiang, Yinjie Wang, Li Sun, Bo Yuan, Yuchen Tian, Lingchao Xiang, Yanying Li, Yong Li, Juan Li, Aiguo Wu
Zeolitic imidazole frameworks (ZIFs) are becoming a notable nanosystem in biomedicine field, due to their unique properties of favorable biocompatibility, pH-responsive degradable structure and high drug loading. Compared with the increasing attention on ZIF-8 in cancer diagnosis and treatment, there is limited research about the bio-application of ZIF-90, especially its in vivo therapeutic efficacy and related toxicity. Here, we synthesize nano ZIF-90 through a fast self-assembling process, and the synthesized nano ZIF-90 is about 75 nm with a negative zeta potential, providing better mitochondria targetability, cell biocompatibility and in vivo survival rate comparing to nano ZIF-8...
January 4, 2019: Biomaterials
Yan Li, Kum-Hee Yun, Hyeri Lee, Sung-Ho Goh, Yang-Gun Suh, Yongdoo Choi
Radiotherapy (RT), along with surgery and chemotherapy, is a major modality of cancer therapy. Nevertheless, insufficient deposition of radiation energy in tumors and hypoxia-associated radioresistance remain the greatest challenges in RT. Here, we propose porous platinum nanoparticles as a new nanomedicine platform for solving these two problems at the same time using a single agent. Because of the combined advantages of a high-Z element and oxygen generation capability, porous platinum nanoparticles can significantly increase radiation-induced DNA damage, ROS stress, and cell cycle arrest by effectively depositing X-ray radiation energy within the cancer cells...
January 4, 2019: Biomaterials
Ping Zhou, Jiaqi Qin, Ce Zhou, Guoyun Wan, Yuanyuan Liu, Mingming Zhang, Xiaoying Yang, Ning Zhang, Yinsong Wang
Copper plays an important role in tumor growth and metastasis. Copper chelation has been confirmed to be an effective strategy for breast cancer therapy through antiangiogenesis. In this work, a copper chelating coil-comb block copolymer RGD-PEG-b-PGA-g-(TETA-DTC-PHis) (RPTDH) was synthesized and used to prepare nanoparticles for loading resiquimod (R848), a TLR7 and TLR8 agonist, thus to combine antiangiogenesis and immune activation to treat breast cancer. RPTDH has strong copper-chelating ability and could self-assemble to form spherical nanoparticles with significant pH-sensitivity...
January 4, 2019: Biomaterials
Hong Cheng, Xue-Yan Jiang, Rong-Rong Zheng, Sheng-Jia Zuo, Lin-Ping Zhao, Gui-Ling Fan, Bo-Ru Xie, Xi-Yong Yu, Shi-Ying Li, Xian-Zheng Zhang
Targeted drug delivery with precisely controlled drug release and activation is highly demanding and challenging for tumor precision therapy. Herein, a biomimetic cascade nanoreactor (designated as Mem@GOx@ZIF-8@BDOX) is constructed for tumor targeted starvation therapy-amplified chemotherapy by assembling tumor cell membrane cloak and glucose oxidase (GOx) onto zeolitic imidazolate framework (ZIF-8) with the loading prodrug of hydrogen peroxide (H2 O2 )-sensitive BDOX. Biomimetic membrane camouflage affords superior immune evasion and homotypic binding capacities, which significantly enhance the tumor preferential accumulation and uptake for targeted drug delivery...
January 3, 2019: Biomaterials
Brooke A Pereira, Natalie L Lister, Kohei Hashimoto, Linda Teng, Maria Flandes-Iparraguirre, Angelina Eder, Alvaro Sanchez-Herrero, Birunthi Niranjan
The tumour microenvironment plays a vital role in the development of solid malignancies. Here we describe an in vitro human prostate cancer microtissue model that facilitates the incorporation and interrogation of key elements of the local prostatic tumour microenvironment. Primary patient-derived cancer-associated fibroblasts (CAFs) were cultured in three-dimensional (3D) melt electrowritten scaffolds where they deposited extensive extracellular matrix (ECM) and promoted significant changes in prostate epithelial morphology, when compared to matched non-malignant prostatic fibroblasts (NPFs)...
January 2, 2019: Biomaterials
J R Eles, A L Vazquez, T D Y Kozai, X T Cui
Meningeal inflammation and encapsulation of neural electrode arrays is a leading cause of device failure, yet little is known about how it develops over time or what triggers it. This work characterizes the dynamic changes of meningeal inflammatory cells and collagen-I in order to understand the meningeal tissue response to neural electrode implantation. We use in vivo two-photon microscopy of CX3CR1-GFP mice over the first month after electrode implantation to quantify changes in inflammatory cell behavior as well as meningeal collagen-I remodeling...
December 31, 2018: Biomaterials
Wei Yin, Wendong Ke, Weijian Chen, Longchang Xi, Qinghao Zhou, Jean Felix Mukerabigwi, Zhishen Ge
In tumor tissues, reactive oxygen species (ROS) level is significantly higher than that in normal tissues, which has been frequently explored as the specific stimulus to trigger drug release. However, the low intrinsic ROS concentration and heterogeneous distribution in tumor tissues hinder the applications as the stimulus for drug delivery. Herein, we developed integrated nanoparticles to remold tumor microenvironment via specific amplification of the tumor oxidative stress and simultaneously realize ROS-responsive drug release...
December 29, 2018: Biomaterials
Jizong Yao, Yao Liu, Jiawen Wang, Qin Jiang, Dejun She, Huishu Guo, Nianrong Sun, Zhiqing Pang, Chunhui Deng, Wuli Yang, Shun Shen
Carbon monoxide (CO) gas therapy combined with chemotherapy and photothermal therapy (PTT) is a promising treatment mode for malignant tumor. Herein, we firstly reported doxorubicin (DOX) loaded Mn carbonyl modified Fe (Ⅲ)-based nanoMOFs (MIL-100) coated PEGylated magnetic carbon nanoparticles (denoted as MCM@PEG-CO-DOX NPs) as theranostics nanoplatforms for near-infrared (NIR)-responded CO-DOX combination therapy. MIL-100 as a good nanocarrier of DOX with high loading capacity can also chelate the Mn carbonyl after a smart modification...
December 28, 2018: Biomaterials
Guan-Hua Lu, Wen-Ting Shang, Han Deng, Zi-Yu Han, Min Hu, Xiao-Yuan Liang, Chi-Hua Fang, Xin-Hong Zhu, Ying-Fang Fan, Jie Tian
Pancreatic cancer is one of the most lethal malignancies worldwide. The existing therapeutic regimen in the clinic for advanced inoperable carcinomas are far from satisfactory, thus it is urgent to seek more effective anticancer strategies. In the pursuit of novel, more effective interventions, photothermal therapy (PTT) based on nanomaterials has attracted increased attention. Recent advances in related fields have catalyzed the generation of novel nanoprobes, such as organic dyes, metal nanoparticles. However, organic dyes are poorly stable and easy to quench while metal nanoparticles with potential metal toxicity are difficult to degrade, both of which have low light-to-heat conversion efficiency, broad spectrum of anti-tumor effects, and lack of tumor targeting specificity...
December 26, 2018: Biomaterials
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