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Jing Wang, Xia-Chao Chen, Yun-Fan Xue, Mi Hu, Yun-Bing Wang, Ke-Feng Ren, Jian Ji
Medical coatings cooperated with biomacromolecules can regulate biological events and tissue responses, thus increasing medical implant longevity and providing improved and/or new therapeutic functions. In particular, medical coatings, which can load the correct species and doses of biomacromolecules according to individual diagnoses, will significantly optimize treatment effects and satisfy the rising clinical need of "precision medicine". Herein, we report on a dynamic microporous coating with an ultrafast self-healing property to fulfill the "load-and-play" concept for "precision medicine"...
November 2, 2018: Biomaterials
Luo-Yuan Li, Yi-Ming Zhou, Rong-Yao Gao, Xiao-Chen Liu, Hui-Hui Du, Jia-Ling Zhang, Xi-Cheng Ai, Jian-Ping Zhang, Li-Min Fu, Leif H Skibsted
Phototherapy has drawn increasing attention including the use of nanocarriers with high drug loading capacity and delivery efficacy for target-specific therapy. We have made use of naturally-occurring halloysite nanotubes (HNTs) to build a biomimetic nanocarrier platform for target-specific delivery of phototherapeutic agents. The HNTs were decorated with poly(sodium-p-styrenesulfonate) (PSS) to enhance the biocompatibility, and were further functionalized by lumen loading the type-II photosensitizer indocyanine green (ICG)...
November 1, 2018: Biomaterials
Xiaomeng Wan, James J Beaudoin, Natasha Vinod, Yuanzeng Min, Naoki Makita, Herdis Bludau, Rainer Jordan, Andrew Wang, Marina Sokolsky, Alexander V Kabanov
Concurrent delivery of multiple drugs using nanoformulations can improve outcomes of cancer treatments. Here we demonstrate that this approach can be used to improve the paclitaxel (PTX) and alkylated cisplatin prodrug combination therapy of ovarian and breast cancer. The drugs are co-loaded in the polymeric micelle system based on amphiphilic block copolymer poly(2-methyl-2-oxazoline-block-2-butyl-2-oxazoline-block-2-methyl-2-oxazoline) (P(MeOx-b-BuOx-b-MeOx). A broad range of drug mixing ratios and exceptionally high two-drug loading of over 50 wt...
October 31, 2018: Biomaterials
Yufei Yan, Hao Chen, Hongbo Zhang, Changjun Guo, Kai Yang, Kaizhe Chen, Ruoyu Cheng, Niandong Qian, Niklas Sandler, Yu Shrike Zhang, Haokai Shen, Jin Qi, Wenguo Cui, Lianfu Deng
3D printed scaffolds hold promising perspective for bone tissue regeneration. Inspired by process of bone development stage, 3D printed scaffolds with rapid internal vascularization ability and robust osteoinduction bioactivity will be an ideal bone substitute for clinical use. Here, we fabricated a 3D printed biodegradable scaffold that can control release deferoxamine, via surface aminolysis and layer-by-layer assembly technique, which is essential for angiogenesis and osteogenesis and match to bone development and reconstruction...
October 31, 2018: Biomaterials
Arnold Leidner, Jens Bauer, Mojtaba Ebrahimi Khonachah, Masanari Takamiya, Uwe Strähle, Thomas Dickmeis, Kersten S Rabe, Christof M Niemeyer
Silica nanoparticles are widely used platform materials for the immobilization of proteins to realize applications in biomedicine and biotechnology. We here report on the use of a highly delicate protein for the systematic evaluation of routes for the surface modification of multifunctional silica nanoparticles. To investigate how surface immobilization methods affect the functionality of surface-bound proteins, we constructed a novel fusion protein, dubbed FlipHOB, that combines the glucose sensor protein FLIP with a variant of the commercially-available self-ligating Halo-tag...
October 31, 2018: Biomaterials
Liya Zhu, Senthilkumar Kalimuthu, Ji Min Oh, Prakash Gangadaran, Se Hwan Baek, Shin Young Jeong, Sang-Woo Lee, Jaetae Lee, Byeong-Cheol Ahn
PURPOSE: Natural killer (NK) cells are the key subset of innate-immunity lymphocytes; they possess antitumor activities and are used for cancer immunotherapy. In a previous study, extracellular vehicles (EVs) from NK-92MI cells were isolated and exploited for their ability to kill human cancer cells in vitro and in vivo (multiple injection methods). Here, the potential of NK-cell-derived EVs (NK-EVs) for immunotherapy was improved by priming with interleukin (IL)-15. METHODS: NK-EVs were isolated from the culture medium without or with IL-15 (NK-EVsIL-15 ) by ultracentrifugation and were purified via density gradient ultracentrifugation...
October 29, 2018: Biomaterials
Inès Mottas, Ahmet Bekdemir, Alessandra Cereghetti, Lorenzo Spagnuolo, Yu-Sang Sabrina Yang, Marie Müller, Darrell J Irvine, Francesco Stellacci, Carole Bourquin
Although immunotherapy shows great promise for the long-term control of cancer, many tumors still fail to respond to treatment. To improve the outcome, the delivery of immunostimulants to the lymph nodes draining the tumor, where the antitumor immune response is initiated, is key. Efforts to use nanoparticles as carriers for cancer immunotherapy have generally required targeting agents and chemical modification of the drug, and have unfortunately resulted in low delivery and therapeutic efficiency. Here, we report on the efficacy of gold nanoparticles with approximately 5 nm hydrodynamic diameter coated with a mixture of 1-octanethiol and 11-mercaptoundecanesulfonic acid for the delivery of an immunostimulatory TLR7 ligand to tumor-draining lymph nodes...
October 25, 2018: Biomaterials
Elizabeth A Aisenbrey, Stephanie J Bryant
Mesenchymal stem cells (MSCs) are promising for cartilage regeneration, but readily undergo terminal differentiation. The aim of this study was two-fold: a) investigate physiochemical cues from a cartilage-mimetic hydrogel under dynamic compressive loading on MSC chondrogenesis and hypertrophy and b) identify whether Smad signaling and p38 MAPK signaling mediate hypertrophy during MSC chondrogenesis. Human MSCs were encapsulated in photoclickable poly(ethylene glycol) hydrogels containing chondroitin sulfate and RGD, cultured under dynamic compressive loading or free swelling for three weeks, and evaluated by qPCR and immunohistochemistry...
October 25, 2018: Biomaterials
Raleigh M Linville, Jackson G DeStefano, Matt B Sklar, Zinnia Xu, Alanna M Farrell, Max I Bogorad, Chengyan Chu, Piotr Walczak, Linzhao Cheng, Vasiliki Mahairaki, Katharine A Whartenby, Peter A Calabresi, Peter C Searson
Microvessels of the blood-brain barrier (BBB) regulate transport into the brain. The highly specialized brain microvascular endothelial cells, a major component of the BBB, express tight junctions and efflux transporters which regulate paracellular and transcellular permeability. However, most existing models of BBB microvessels fail to exhibit physiological barrier function. Here, using (iPSC)-derived human brain microvascular endothelial cells (dhBMECs) within templated type I collagen channels we mimic the cylindrical geometry, cell-extracellular matrix interactions, and shear flow typical of human brain post-capillary venules...
October 25, 2018: Biomaterials
Haishuang Lin, Qiang Li, Qian Du, Ou Wang, Zhanqi Wang, Leonard Akert, Mark A Carlson, Chi Zhang, Anuradha Subramanian, Chi Zhang, Matthew Lunning, Ming Li, Yuguo Lei
Human induced pluripotent stem cells (iPSCs) have unlimited proliferation capability and potential to differentiate into all somatic cells. Their derivatives contain patients' genetic information and can model many diseases. Additionally, derivatives of patient-specific iPSCs induce minimal immune rejection in vivo. With this unique combination of properties, iPSCs open the avenue to personalized medicine including personalized drug screening, toxicity test, cell therapy and tissue engineering. However, the further advance of iPSC-based personalized medicine is currently limited by the difficulty to generate iPSCs for large populations and at affordable cost...
October 25, 2018: Biomaterials
Song Shen, Fei Han, Anran Yuan, Lin Wu, Jin Cao, Jing Qian, Xueyong Qi, Yongsheng Yan, Yanru Ge
Endotoxemia is a severe pathophysiology induced by bacterial endotoxin (also known as lipopolysaccharide, LPS), causing high mortality in clinic due to the life-threatening syndromes, such as sepsis, shock, and multiple organ dysfunction. Removing or neutralizing endotoxin from the circulatory system has been proven to be a potential strategy for the treatment of endotoxemia. However, the selectivity and removal efficiency of existing detoxification approaches are not satisfied. Considering the crucial role of immune cells in LPS recognition and inflammation mediation, we design a disguised nanoparticle using macrophage membranes as bait to specifically capture and deactivate LPS...
October 24, 2018: Biomaterials
Di Shi, Gujie Mi, Mian Wang, Thomas J Webster
Bacterial infections and antibiotic resistant bacteria have become a growing problem over the past decade. As a result, the Centers for Disease Control predict more deaths resulting from microorganisms than all cancers combined by 2050. Currently, many traditional models used to study bacterial infections fail to precisely replicate the in vivo bacterial environment. These models often fail to incorporate fluid flow, bio-mechanical cues, intercellular interactions, host-bacteria interactions, and even the simple inclusion of relevant physiological proteins in culture media...
October 24, 2018: Biomaterials
Wei-Ta Chen, Wei-Tse Hsu, Meng-Hua Yen, Chun A Changou, Chia-Li Han, Yu-Ju Chen, Ji-Yen Cheng, Tzu-Hao Chang, Oscar Kuang-Sheng Lee, Jennifer Hui-Chun Ho
Mesenchymal stem cell (MSC) is mechanosensitive and the respond to mechanical force is pattern specific. We previously reported that oscillatory shear stress at 0.5 ± 4 dyne/cm2 guided MSCs polarity vertical to net flow direction before apolaric stage at 30 min resulting in phosphorylation of β-catenin and inhibition of Wnt signaling. This time, we explored laminar shear stress (LS) at 0.5 dyne/cm2 polarized MSCs by guiding F-actin orientation parallel to the flow direction before apolarity at 30 min accompanied with activation of Wnt signaling...
October 23, 2018: Biomaterials
Joshua T Morgan, Jasmine Shirazi, Erica M Comber, Christian Eschenburg, Jason P Gleghorn
One of the largest challenges facing the field of tissue engineering is the incorporation of a functional vasculature, allowing effective nourishment of graft tissue beyond diffusion length scales. Here, we demonstrate a methodology for inducing the robust self-assembly of endothelial cells into stable three-dimensional perfusable networks on millimeter and centimeter length scales. Utilizing broadly accessible cell strains and reagents, we have rigorously tested a state space of cell densities (0.5-2.0 × 106  cell/mL) and collagen gel densities (2-6 mg/mL) that result in robust vascular network formation...
October 22, 2018: Biomaterials
Ben P Hung, Jenna N Harvestine, Augustine M Saiz, Tomas Gonzalez-Fernandez, David E Sahar, Mark L Weiss, J Kent Leach
The maintenance and direction of stem cell lineage after implantation remains challenging for clinical translation. Aggregation and encapsulation into instructive biomaterials after preconditioning can bolster retention of differentiated phenotypes. Since these procedures do not depend on cell type or lineage, we hypothesized we could use a common, tunable platform to engineer formulations that retain and enhance multiple lineages from different cell populations. To test this, we varied alginate stiffness and adhesive ligand content, then encapsulated spheroids of varying cellularity...
October 22, 2018: Biomaterials
Se-Jeong Kim, Jaesung Park, Hayeon Byun, Young-Woo Park, Luke G Major, Dong Yun Lee, Yu Suk Choi, Heungsoo Shin
Stem cell spheroids have been studied extensively in organoid culture and therapeutic transplantation. Herein, hydrogels with an embossed surface (HES) were developed as an all-in-one platform that can enable the rapid formation and culture of a large quantity of size-controllable stem cell spheroids. The embossed structure on the hydrogel was adjustable according to the grit designation of the sandpaper. Human adipose-derived stem cells (hADSCs) were rapidly assembled into spheroids on the hydrogel, with their size distribution precisely controlled from 95 ± 6 μm to 181 ± 15 μm depending on surface roughness...
October 22, 2018: Biomaterials
Yuan Zhang, Xin Bush, Bingfang Yan, Justin A Chen
Myeloid-derived suppressor cells (MDSCs) promote tumor-mediated immunosuppression and cancer progression. Gemcitabine (Gem) is a MDSC-depleting chemotherapeutic agent; however, its clinical use is hampered by its drug resistance and inefficient in vivo delivery. Here we describe a strategy to formulate a Gem analogue gemcitabine monophosphate (GMP) into a lipid-coated calcium phosphate (LCP) nanoparticle, and investigate its antitumor immunity and therapeutic effects after systemic administrations. In the syngeneic mouse model of B16F10 melanoma, compared with free Gem, the LCP-formulated GMP (LCP-GMP) significantly induced apoptosis and reduced immunosuppression in the tumor microenvironment (TME)...
October 20, 2018: Biomaterials
Yuling Mao, Shuang Feng, Shuai Li, Qinfu Zhao, Donghua Di, Yanfeng Liu, Siling Wang
Lymphatic transport of oral drugs allows extraordinary gains in bioavailability and efficacy through avoidance of first-pass hepatic metabolism and preservation of drugs at lymphatic tissues against lymph-mediated diseases. Chylomicrons can transport dietary lipids absorbed from the intestine to the tissues through lymphatic circulation. Herein, we engineered for the first time a chylomicron-pretended mesoporous silica nanocarrier that utilizes the digestion, re-esterification, and lymphatic transport process of dietary triglyceride to promote lymphatic transport of oral drugs...
October 18, 2018: Biomaterials
Yunfei Li, Yajuan Xiao, Hsuan-Pei Lin, Derek Reichel, Younsoo Bae, Eun Y Lee, Yiguo Jiang, Xuefei Huang, Chengfeng Yang, Zhishan Wang
Cancer stem cells (CSCs) play pivotal roles in cancer metastasis, and strategies targeting cancer stemness may greatly reduce cancer metastasis and improve patients' survival. The canonical Wnt/β-catenin pathway plays critical roles in CSC generation and maintenance as well as in normal stem cells. Non-specifically suppressing the Wnt/β-catenin pathway for cancer therapy could be deleterious to normal cells. To achieve specific β-catenin attenuation in cancer cells, we report an integrin α5 (ITGA5)-targeting nanoparticle for treating metastatic triple negative breast cancer (TNBC)...
October 18, 2018: Biomaterials
Cassie Bennett, Farrah Mohammed, Anabel Álvarez-Ciara, Michelle A Nguyen, W Dalton Dietrich, Suhrud M Rajguru, Wolfgang J Streit, Abhishek Prasad
The use of intracortical microelectrode arrays has gained significant attention in being able to help restore function in paralysis patients and study the brain in various neurological disorders. Electrode implantation in the cortex causes vasculature or blood-brain barrier (BBB) disruption and thus elicits a foreign body response (FBR) that results in chronic inflammation and may lead to poor electrode performance. In this study, a comprehensive insight into the acute molecular mechanisms occurring at the Utah electrode array-tissue interface is provided to understand the oxidative stress, neuroinflammation, and neurovascular unit (astrocytes, pericytes, and endothelial cells) disruption that occurs following microelectrode implantation...
October 18, 2018: Biomaterials
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