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Acta Biomaterialia: structure-property-function re... 29건

  1. [해외논문]   Editorial Board   SCI SCIE SCOPUS


    Acta Biomaterialia: structure-property-function relationships in biomaterials v.70 ,pp. i - i , 2018 , 1742-7061 ,

    초록

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  2. [해외논문]   Cell-material interactions in tendon tissue engineering   SCI SCIE SCOPUS

    Lin, Junxin (Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, China ) , Zhou, Wenyan (Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, China ) , Han, Shan (Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, China ) , Bunpetch, Varitsara (Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, China ) , Zhao, Kun (Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, China ) , Liu, Chaozhong (Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, China ) , Yin, Zi (Dr. Li Dak Sum & Yip Yio Chi) , Ouyang, Hongwei
    Acta Biomaterialia: structure-property-function relationships in biomaterials v.70 ,pp. 1 - 11 , 2018 , 1742-7061 ,

    초록

    Abstract The interplay between cells and materials is a fundamental topic in biomaterial-based tissue regeneration. One of the principles for biomaterial development in tendon regeneration is to stimulate tenogenic differentiation of stem cells. To this end, efforts have been made to optimize the physicochemical and bio-mechanical properties of biomaterials for tendon tissue engineering. However, recent progress indicated that innate immune cells, especially macrophages, can also respond to the material cues and undergo phenotypical changes, which will either facilitate or hinder tissue regeneration. This process has been, to some extent, neglected by traditional strategies and may partially explain the unsatisfactory outcomes of previous studies; thus, more researchers have turned their focus on developing and designing immunoregenerative biomaterials to enhance tendon regeneration. In this review, we will first summarize the effects of material cues on tenogenic differentiation and paracrine secretion of stem cells. A brief introduction will also be made on how material cues can be manipulated for the regeneration of tendon-to-bone interface. Then, we will discuss the characteristics and influences of macrophages on the repair process of tendon healing and how they respond to different materials cues. These principles may benefit the development of novel biomaterials provided with combinative bioactive cues to activate tenogenic differentiation of stem cells and pro-resolving macrophage phenotype. Statement of Significance The progress achieved with the rapid development of biomaterial-based strategies for tendon regeneration has not yielded broad benefits to clinical patients. In addition to the interplay between stem cells and biomaterials, the innate immune response to biomaterials also plays a determinant role in tissue regeneration. Here, we propose that fine-tuning of stem cell behaviors and alternative activation of macrophages through material cues may lead to effective tendon/ligament regeneration. We first review the characteristics of key material cues that have been manipulated to promote tenogenic differentiation and paracrine secretion of stem cells in tendon regeneration. Then, we discuss the potentiality of corresponding material cues in activating macrophages toward a pro-resolving phenotype to promote tissue repair. Graphical abstract [DISPLAY OMISSION]

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    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  3. [해외논문]   In vitro methods for the evaluation of antimicrobial surface designs   SCI SCIE SCOPUS

    Sjollema, Jelmer (University of Groningen, University Medical Center Groningen, Department of BioMedical Engineering, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands ) , Zaat, Sebastian A.J. (Department of Medical Microbiology, CINIMA (Center for Infection and Immunity Amsterdam), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands ) , Fontaine, Veronique (Unit of Pharmaceutical Microbiology and Hygiene, Faculty of Pharmacy, Université) , Ramstedt, Madeleine (Libre de Bruxelles (ULB), Campus Plaine, Boulevard du Triomphe, 1050 Brussels, Belgium ) , Luginbuehl, Reto (Department of Chemistry, Umeå) , Thevissen, Karin (University, SE-901 87 Umeå, Sweden ) , Li, Jiuyi (RMS Foundation, Bischmattstrasse 12, 2544 Bettlach, Switzerland ) , van der Mei, Henny C. (Centre for Microbial and Plant Genetics, CMPG, University of Leuven, Kasteelpark Arenberg 20, 3001 Heverlee, Belgium ) , Busscher, Henk J. (School of Civil Engineering, Beijing Jiaotong University, 3 Shangyuancun, Xizhimenwai, Beijing 100044, China )
    Acta Biomaterialia: structure-property-function relationships in biomaterials v.70 ,pp. 12 - 24 , 2018 , 1742-7061 ,

    초록

    Abstract Bacterial adhesion and subsequent biofilm formation on biomedical implants and devices are a major cause of their failure. As systemic antibiotic treatment is often ineffective, there is an urgent need for antimicrobial biomaterials and coatings. The term “antimicrobial” can encompass different mechanisms of action (here termed “antimicrobial surface designs”), such as antimicrobial-releasing, contact-killing or non-adhesivity. Biomaterials equipped with antimicrobial surface designs based on different mechanisms of action require different in vitro evaluation methods. Available industrial standard evaluation tests do not address the specific mechanisms of different antimicrobial surface designs and have therefore been modified over the past years, adding to the myriad of methods available in the literature to evaluate antimicrobial surface designs. The aim of this review is to categorize fourteen presently available methods including industrial standard tests for the in vitro evaluation of antimicrobial surface designs according to their suitability with respect to their antimicrobial mechanism of action. There is no single method or industrial test that allows to distinguish antimicrobial designs according to all three mechanisms identified here. However, critical consideration of each method clearly relates the different methods to a specific mechanism of antimicrobial action. It is anticipated that use of the provided table with the fourteen methods will avoid the use of wrong methods for evaluating new antimicrobial designs and therewith facilitate translation of novel antimicrobial biomaterials and coatings to clinical use. The need for more and better updated industrial standard tests is emphasized. Statement of Significance European COST-action TD1305, IPROMEDAI aims to provide better understanding of mechanisms of antimicrobial surface designs of biomaterial implants and devices. Current industrial evaluation standard tests do not sufficiently account for different, advanced antimicrobial surface designs, yet are urgently needed to obtain convincing in vitro data for approval of animal experiments and clinical trials. This review aims to provide an innovative and clear guide to choose appropriate evaluation methods for three distinctly different mechanisms of antimicrobial design: (1) antimicrobial-releasing, (2) contact-killing and (3) non-adhesivity. Use of antimicrobial evaluation methods and definition of industrial standard tests, tailored toward the antimicrobial mechanism of the design, as identified here, fulfill a missing link in the translation of novel antimicrobial surface designs to clinical use. Graphical abstract [DISPLAY OMISSION]

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  4. [해외논문]   Challenges in vascular tissue engineering for diabetic patients   SCI SCIE SCOPUS

    Dhulekar, Jhilmil (Corresponding author at: Clemson University, Department of Bioengineering, 301 Rhodes Hall, Clemson, SC 29634, United States.) , Simionescu, Agneta
    Acta Biomaterialia: structure-property-function relationships in biomaterials v.70 ,pp. 25 - 34 , 2018 , 1742-7061 ,

    초록

    Abstract Hyperglycemia and dyslipidemia coexist in diabetes and result in inflammation, degeneration, and impaired tissue remodeling, processes which are not conducive to the desired integration of tissue engineered products into the surrounding tissues. There are several challenges for vascular tissue engineering such as non-thrombogenicity, adequate burst pressure and compliance, suturability, appropriate remodeling responses, and vasoactivity, but, under diabetic conditions, an additional challenge needs to be considered: the aggressive oxidative environment generated by the high glucose and lipid concentrations that lead to the formation of advanced glycation end products (AGEs) in the vascular wall. Extracellular matrix-based scaffolds have adequate physical properties and are biocompatible, however, these scaffolds are altered in diabetes by the formation AGEs and impaired collagen degradation, consequently increasing vascular wall stiffness. In addition, vascular cells detect and respond to altered stimuli from the matrix by pathological remodeling of the vascular wall. Due to the immunomodulatory effects of mesenchymal stem cells (MSCs), they are frequently used in tissue engineering in order to protect the scaffolds from inflammation. MSCs together with antioxidant treatments of the scaffolds are expected to protect the vascular grafts from diabetes-induced alterations. In conclusion, as one of the most daunting environments that could damage the ECM and its interaction with cells is progressively built in diabetes, we recommend that cells and scaffolds used in vascular tissue engineering for diabetic patients are tested in diabetic animal models, in order to obtain valuable results regarding their resistance to diabetic adversities. Statement of Significance Almost 25 million Americans have diabetes, characterized by high levels of blood sugar that binds to tissues and disturbs the function of cardiovascular structures. Therefore, patients with diabetes have a high risk of cardiovascular diseases. Surgery is required to replace diseased arteries with implants, but these fail after 5–10 years because they are made of non-living materials, not resistant to diabetes. New tissue engineering materials are developed, based on the patients’ own stem cells, isolated from fat, and added to extracellular matrix-based scaffolds. Our main concern is that diabetes could damage the tissue-like implants. Thus we review studies related to the effect of diabetes on tissue components and recommend antioxidant treatments to increase the resistance of implants to diabetes. Graphical abstract [DISPLAY OMISSION]

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    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  5. [해외논문]   Nanoengineered injectable hydrogels for wound healing application   SCI SCIE SCOPUS

    Lokhande, Giriraj (Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, United States ) , Carrow, James K. (Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, United States ) , Thakur, Teena (Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, United States ) , Xavier, Janet R. (Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, United States ) , Parani, Madasamy (Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, United States ) , Bayless, Kayla J. (Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, TX 77843, United States ) , Gaharwar, Akhilesh K. (Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, United States)
    Acta Biomaterialia: structure-property-function relationships in biomaterials v.70 ,pp. 35 - 47 , 2018 , 1742-7061 ,

    초록

    Abstract We report injectable nanoengineered hemostats for enhanced wound healing and tissue regeneration. The nanoengineered system consists of the natural polysaccharide, κ-carrageenan (κCA), loaded with synthetic two-dimensional (2D) nanosilicates. Nanoengineered hydrogels showed shear-thinning characteristics and can be injected for minimally invasive approaches. The injectable gels can be physically crosslinked in presence of monovalent ions to form mechanically strong hydrogels. By controlling the ratio between κCA and nanosilicates, compressive stiffness of crosslinked hydrogels can be modulated between 20 and 200 kPa. Despite high mechanical stiffness, nanocomposite hydrogels are highly porous with an interconnected network. The addition of nanosilicates to κCA increases protein adsorption on nanocomposite hydrogels that results in enhance cell adhesion and spreading, increase platelets binding and reduce blood clotting time. Moreover, due to presence of nanosilicates, a range of therapeutic biomacromolecules can be deliver in a sustain manner. The addition of nanosilicates significantly suppresses the release of entrap vascular endothelial growth factor (VEGF) and facilitate in vitro tissue regeneration and wound healing. Thus, this multifunctional nanocomposite hydrogel can be used as an injectable hemostat and an efficient vehicle for therapeutic delivery to facilitate tissue regeneration. Statement of Significance Hemorrhage is a leading cause of death in battlefield wounds, anastomosis hemorrhage and percutaneous intervention. Thus, there is a need for the development of novel bioactive materials to reduce the likelihood of hemorrhagic shock stemming from internal wounds. Here, we introduce an injectable hemostat from kappa-carrageenan and two-dimensional (2D) nanosilicates. Nanosilicates mechanically reinforce the hydrogels, provide enhanced physiological stability and accelerate the clotting time by two-fold. The sustained release of entrapped therapeutics due to presence of nanosilicates promotes enhanced wound healing. The multifunctional nanocomposite hydrogels could be used as an injectable hemostat for penetrating injury and percutaneous intervention during surgery. Graphical abstract [DISPLAY OMISSION]

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    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  6. [해외논문]   3D bioprinted functional and contractile cardiac tissue constructs   SCI SCIE SCOPUS

    Wang, Zhan (Corresponding author.) , Lee, Sang Jin , Cheng, Heng-Jie , Yoo, James J. , Atala, Anthony
    Acta Biomaterialia: structure-property-function relationships in biomaterials v.70 ,pp. 48 - 56 , 2018 , 1742-7061 ,

    초록

    Abstract Bioengineering of a functional cardiac tissue composed of primary cardiomyocytes has great potential for myocardial regeneration and in vitro tissue modeling. However, its applications remain limited because the cardiac tissue is a highly organized structure with unique physiologic, biomechanical, and electrical properties. In this study, we undertook a proof-of-concept study to develop a contractile cardiac tissue with cellular organization, uniformity, and scalability by using three-dimensional (3D) bioprinting strategy. Primary cardiomyocytes were isolated from infant rat hearts and suspended in a fibrin-based bioink to determine the priting capability for cardiac tissue engineering. This cell-laden hydrogel was sequentially printed with a sacrificial hydrogel and a supporting polymeric frame through a 300-μm nozzle by pressured air. Bioprinted cardiac tissue constructs had a spontaneous synchronous contraction in culture, implying in vitro cardiac tissue development and maturation. Progressive cardiac tissue development was confirmed by immunostaining for α-actinin and connexin 43, indicating that cardiac tissues were formed with uniformly aligned, dense, and electromechanically coupled cardiac cells. These constructs exhibited physiologic responses to known cardiac drugs regarding beating frequency and contraction forces. In addition, Notch signaling blockade significantly accelerated development and maturation of bioprinted cardiac tissues. Our results demonstrated the feasibility of bioprinting functional cardiac tissues that could be used for tissue engineering applications and pharmaceutical purposes. Statement of Significance Cardiovascular disease remains a leading cause of death in the United States and a major health-care burden. Myocardial infarction (MI) is a main cause of death in cardiovascular diseases. MI occurs as a consequence of sudden blocking of blood vessels supplying the heart. When occlusions in the coronary arteries occur, an immediate decrease in nutrient and oxygen supply to the cardiac muscle, resulting in permanent cardiac cell death. Eventually, scar tissue formed in the damaged cardiac muscle that cannot conduct electrical or mechanical stimuli thus leading to a reduction in the pumping efficiency of the heart. The therapeutic options available for end-stage heart failure is to undergo heart transplantation or the use of mechanical ventricular assist devices (VADs). However, many patients die while being on a waiting list, due to the organ shortage and limitation of VADs, such as surgical complications, infection, thrombogenesis, and failure of the electrical motor and hemolysis. Ultimately, 3D bioprinting strategy aims to create clinically applicable tissue constructs that can be immediately implanted in the body. To date, the focus on replicating complex and heterogeneous tissue constructs continues to increase as 3D bioprinting technologies advance. In this study, we demonstrated the feasibility of 3D bioprinting strategy to bioengineer the functional cardiac tissue that possesses a highly organized structure with unique physiological and biomechanical properties similar to native cardiac tissue. This bioprinting strategy has great potential to precisely generate functional cardiac tissues for use in pharmaceutical and regenerative medicine applications. Graphical abstract [DISPLAY OMISSION]

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  7. [해외논문]   Cell reprogramming by 3D bioprinting of human fibroblasts in polyurethane hydrogel for fabrication of neural-like constructs   SCI SCIE SCOPUS

    Ho, Lin (Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan, ROC ) , Hsu, Shan-hui (Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan, ROC)
    Acta Biomaterialia: structure-property-function relationships in biomaterials v.70 ,pp. 57 - 70 , 2018 , 1742-7061 ,

    초록

    Abstract 3D bioprinting is a technique which enables the direct printing of biodegradable materials with cells into 3D tissue. So far there is no cell reprogramming in situ performed with the 3D bioprinting process. Forkhead box D3 (FoxD3) is a transcription factor and neural crest marker, which was reported to reprogram human fibroblasts into neural crest stem-like cells. In this study, we synthesized a new biodegradable thermo-responsive waterborne polyurethane (PU) gel as a bioink. FoxD3 plasmids and human fibroblasts were co-extruded with the PU hydrogel through the syringe needle tip for cell reprogramming. The rheological properties of the PU hydrogel including the modulus, gelation time, and shear thinning were optimized for the transfection effect of FoxD3 in situ . The corresponding shear rate and shear stress were examined. Results showed that human fibroblasts could be reprogrammed into neural crest stem-like cells with high cell viability during the extrusion process under an average shear stress ∼190 Pa. We further translated the method to the extrusion-based 3D bioprinting, and demonstrated that human fibroblasts co-printed with FoxD3 in the thermo-responsive PU hydrogel could be reprogrammed and differentiated into a neural-tissue like construct at 14 days after induction. The neural-like tissue construct produced by 3D bioprinting from human fibroblasts may be applied to personalized drug screening or neuroregeneration. Statement of Significance There is no study so far on cell reprogramming in situ with 3D bioprinting. In this manuscript, a new thermoresponsive polyurethane bioink was developed and employed to deliver FoxD3 plasmid into human fibroblasts by the extrusion-based bioprinting. When the polyurethane gel was extruded through the syringe tip, the shear stress generated may have caused the transient membrane permeability for transfection. The shear stress was optimized for transfection in situ by 3D bioprinting. We demonstrated that human fibroblasts could be reprogrammed into neural crest-like stem cells by 3D bioprinting with the gel, and the reprogrammed cells underwent neural differentiation in the printed structure after induction. The neural-like tissue engineering constructs fabricated by 3D bioprinting from human fibroblasts may be applied for neuroregeneration or further developed as mini-brain for basic research and drug screening. Graphical abstract [DISPLAY OMISSION]

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    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  8. [해외논문]   Synthetic extracellular matrix mimic hydrogel improves efficacy of mesenchymal stromal cell therapy for ischemic cardiomyopathy   SCI SCIE SCOPUS

    Ciuffreda, Maria Chiara (Department of Medical Sciences and Infectious Diseases –) , Malpasso, Giuseppe (Coronary Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy ) , Chokoza, Cindy (Department of Medical Sciences and Infectious Diseases –) , Bezuidenhout, Deon (Coronary Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy ) , Goetsch, Kyle P. (Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town, Department of Health Sciences, Cape Town, South Africa ) , Mura, Manuela (Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town, Department of Health Sciences, Cape Town, South Africa ) , Pisano, Federica (Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town, Department of Health Sciences, Cape Town, South Africa ) , Davies, Neil H. (Department of Medical Sciences and Infectious Diseases –) , Gnecchi, Massimiliano (Coronary Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy )
    Acta Biomaterialia: structure-property-function relationships in biomaterials v.70 ,pp. 71 - 83 , 2018 , 1742-7061 ,

    초록

    Abstract Background Mesenchymal stromal cells (MSC) repair infarcted hearts mainly through paracrine mechanisms. Low cell engraftment limits the release of soluble paracrine factors (SF) over time and, consequently, MSC efficacy. We tested whether a synthetic extracellular matrix mimic, a hydrogel containing heparin (H-HG), could ameliorate MSC engraftment and binding/release of SF, thus improving MSC therapy efficacy. Methods and results In vitro , rat bone-marrow MSC (rBM-MSC) were seeded and grown into H-HG. Under normoxia, the hydrogel did not affect cell survival (rBM-MSC survival >90% at each time point tested); vice versa, under hypoxia the biomaterial resulted to be protective for the cells (p vs rBM-MSC alone). H-HG or control PEG hydrogels (HG) were incubated with VEGF or bFGF for binding/release quantification. Data showed significantly higher amount of VEGF and bFGF bound by H-HG compared with HG (p In vivo , myocardial infarction (MI) was induced in female Sprague Dawley rats by permanent coronary ligation. One week later, saline, rBM-MSC, H-HG or rBM-MSC/H-HG were injected in the infarct zone. The co-injection of rBM-MSC/H-HG into infarcted hearts significantly increased cardiac function. Importantly, we observed a significant gain in MSC engraftment, reduction of ventricular remodeling and stimulation of neo-vasculogenesis. We also documented higher amounts of several pro-angiogenic factors in hearts treated with rBM-MSC/H-HG. Conclusions Our data show that H-HG increases MSC engraftment, efficiently fine tunes the paracrine MSC actions and improves cardiac function in infarcted rat hearts. Statement of Significance Transplantation of MSC is a promising treatment for ischemic heart disease, but low cell engraftment has so far limited its efficacy. The enzymatically degradable H-HG that we developed is able to increase MSC retention/engraftment and, at the same time, to fine-tune the paracrine effects mediated by the cells. Most importantly, the co-transplantation of MSC and H-HG in a rat model of ischemic cardiomyopathy improved heart function through a significant reduction in ventricular remodeling/scarring and amelioration in neo-vasculogenesis/endogenous cardiac regeneration. These beneficial effects are comparable to those obtained by others using a much greater number of cells, strengthening the efficacy of the biomaterial used in increasing the therapeutic effects of MSC. Given its efficacy and safety, documented by the absence of immunoreaction, our strategy appears readily translatable to clinical scenarios. Graphical abstract [DISPLAY OMISSION]

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  9. [해외논문]   A physiologically relevant 3D collagen-based scaffold–neuroblastoma cell system exhibits chemosensitivity similar to orthotopic xenograft models   SCI SCIE SCOPUS

    Curtin, C. (Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland ) , Nolan, J.C. (Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland ) , Conlon, R. (Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland ) , Deneweth, L. (Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland ) , Gallagher, C. (Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland ) , Tan, Y.J. (Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland ) , Cavanagh, B.L. (Cellular and Molecular Imaging Core, Royal College of Surgeons in Ireland, Dublin, Ireland ) , Asraf, A.Z. (Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland ) , Harvey, H. (Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland ) , Miller-Delaney, S. (Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland ) , Shohet, J. (Department of Pediatrics, Section of Hematology-Oncology, Baylor Colle) , Bray, I. , O'Brien, F.J. , Stallings, R.L. , Piskareva, O.
    Acta Biomaterialia: structure-property-function relationships in biomaterials v.70 ,pp. 84 - 97 , 2018 , 1742-7061 ,

    초록

    Abstract 3D scaffold-based in vitro cell culturing is a recent technological advancement in cancer research bridging the gap between conventional 2D culture and in vivo tumours. The main challenge in treating neuroblastoma, a paediatric cancer of the sympathetic nervous system, is to combat tumour metastasis and resistance to multiple chemotherapeutic drugs. The aim of this study was to establish a physiologically relevant 3D neuroblastoma tissue-engineered system and explore its therapeutic relevance. Two neuroblastoma cell lines, chemotherapeutic sensitive Kelly and chemotherapeutic resistant KellyCis83 were cultured in a 3D in vitro model on two collagen-based scaffolds containing either glycosaminoglycan (Coll-GAG) or nanohydroxyapatite (Coll-nHA) and compared to 2D cell culture and an orthotopic murine model. Both neuroblastoma cell lines actively infiltrated the scaffolds and proliferated displaying >100-fold increased resistance to cisplatin treatment when compared to 2D cultures, exhibiting chemosensitivity similar to orthotopic xenograft in vivo models. This model demonstrated its applicability to validate miRNA-based gene delivery. The efficacy of liposomes bearing miRNA mimics uptake and gene knockdown was similar in both 2D and 3D in vitro culturing models highlighting the proof-of-principle for the applicability of 3D collagen-based scaffolds cell system for validation of miRNA function. Collectively, this data shows the successful development and characterisation of a physiologically relevant, scaffold-based 3D tissue-engineered neuroblastoma cell model, strongly supporting its value in the evaluation of chemotherapeutics, targeted therapies and investigation of neuroblastoma pathogenesis. While neuroblastoma is the specific disease being focused upon, the platform may have multi-functionality beyond this tumour type. Statement of Significance Traditional 2D cell cultures do not completely capture the 3D architecture of cells and extracellular matrix contributing to a gap in our understanding of mammalian biology at the tissue level and may explain some of the discrepancies between in vitro and in vivo results. Here, we demonstrated the successful development and characterisation of a physiologically relevant, scaffold-based 3D tissue-engineered neuroblastoma cell model, strongly supporting its value in the evaluation of chemotherapeutics, targeted therapies and investigation of neuroblastoma pathogenesis. The ability to test drugs in this reproducible and controllable tissue-engineered model system will help reduce the attrition rate of the drug development process and lead to more effective and tailored therapies. Importantly, such 3D cell models help to reduce and replace animals for pre-clinical research addressing the principles of the 3Rs. Graphical abstract [DISPLAY OMISSION]

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  10. [해외논문]   Mechanically enhanced nested-network hydrogels as a coating material for biomedical devices   SCI SCIE SCOPUS

    Wang, Zhengmu (Department of Mechanical Engineering, University of British Columbia, Vancouver, BC V6T 1Z4, Canada ) , Zhang, Hongbin (Department of Mechanical Engineering, University of British Columbia, Vancouver, BC V6T 1Z4, Canada ) , Chu, Axel J. (Department of Mechanical Engineering, University of British Columbia, Vancouver, BC V6T 1Z4, Canada ) , Jackson, John (Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z4, Canada ) , Lin, Karen (The Stone Centre at Vancouver General Hospital, Department of Urologic Sciences, University of British Columbia, Jack Bell Research Centre, Vancouver, BC V6H 3Z6, Canada ) , Lim, Chinten James (BC Children's Hospital Research Institute and Department of Pediatrics, University of British Columbia, Vancouver, BC V5Z 4H4, Canada ) , Lange, Dirk (The Stone Centre at Vancouver General Hospital, Department of Urologic Sciences, University of British Columbia, Jack Bell Research Centre, Vancouver, BC V6H 3Z6, Canada ) , Chiao, Mu (Department of Mechanical Engineering, University of British Columbia, Vancouver, BC V6T 1Z4, Canada)
    Acta Biomaterialia: structure-property-function relationships in biomaterials v.70 ,pp. 98 - 109 , 2018 , 1742-7061 ,

    초록

    Abstract Well-organized composite formations such as hierarchical nested-network (NN) structure in bone tissue and reticular connective tissue present remarkable mechanical strength and play a crucial role in achieving physical and biological functions for living organisms. Inspired by these delicate microstructures in nature, an analogous scaffold of double network hydrogel was fabricated by creating a poly(2-hydroxyethyl methacrylate) (pHEMA) network in the porous structure of alginate hydrogels. The resulting hydrogel possessed hierarchical NN structure and showed significantly improved mechanical strength but still maintained high elasticity comparable to soft tissues due to a mutual strengthening effect between the two networks. The tough hydrogel is also self-lubricated, exhibiting a surface friction coefficient comparable with polydimethylsiloxane (PDMS) substrates lubricated by a commercial aqueous lubricant (K-Y Jelly) and other low surface friction hydrogels. Additional properties of this hydrogel include high hydrophilicity, good biocompatibility, tunable cell adhesion and bacterial resistance after incorporation of silver nanoparticles. Firm bonding of the hydrogel on silicone substrates could be achieved through facile chemical modification, thus enabling the use of this hydrogel as a versatile coating material for biomedical applications. Statement of Significance In this study, we developed a tough hydrogel by crosslinking HEMA monomers in alginate hydrogels and forming a well-organized structure of hierarchical nested network (NN). Different from most reported stretchable alginate-based hydrogels, the NN hydrogel shows higher compressive strength but retains comparable softness to alginate counterparts. This work further demonstrated the good integration of the tough hydrogel with silicone substrates through chemical modification and micropillar structures. Other properties including surface friction, biocompatibility and bacterial resistance were investigated and the hydrogel shows a great promise as a versatile coating material for biomedical applications. Graphical abstract [DISPLAY OMISSION]

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