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1. 发明申请

WO2012031144A2 SILK FIBROIN AND POLYETHYLENE GLYCOL-BASED BIOMATERIALS 审中-公开
标题翻译：蚕丝蛋白和基于聚乙二醇的生物材料
公开(公告)号：WO2012031144A2
公开(公告)日：2012-03-08
申请号：PCT/US2011/050238
申请日：2011-09-01
申请人： TRUSTEES OF TUFTS COLLEGE , KAPLAN, David L. , SERBAN, Monica A.
发明人： KAPLAN, David L. , SERBAN, Monica A.
IPC分类号： A61L27/44 , A61L27/14 , A61L27/22 , A61L27/52 , A61L27/54 , A61L27/38
CPC分类号： A61L24/108 , A61L24/0094 , A61L27/26 , A61L27/52 , A61L27/54 , A61L2300/406 , C08L71/02 , C08L77/04 , C08L89/00 , C08L89/06
摘要： This invention relates to methods and compositions for preparation of silk-PEGs based biomaterials through crosslinking by chemically reacting active polyethylene glycols (PEGs) possessing different chemical groups (e.g., thiols and maleimides functionalized PEGs) that are additionally stabilized by the beta-sheet formation of silk fibroin. The crosslinked silk-PEGs biomaterials present strong adhesive properties, which are comparable to or better than the current leading PEG-based sealant, depending on the silk concentration in the silk-PEGs biomaterials. In addition, the silk-PEGs based biomaterials are cytocompatible, show decreased swelling behavior and longer degradation times, which make them suitable for hemostatic applications where the current available tissue sealant products can be contraindicated.
摘要翻译：本发明涉及用于通过使另外具有不同化学基团的活性聚乙二醇（PEG）（例如，硫醇和马来酰亚胺官能化的PEG）化学反应，通过交联制备基于丝-PEG的生物材料的方法和组合物通过丝素蛋白的β折叠形成而稳定。交联的丝-PEG生物材料呈现出强粘合性能，这与当前领先的PEG基密封剂相当或更好，这取决于丝-PEG生物材料中的丝绸浓度。此外，基于丝-PEG的生物材料具有细胞相容性，表现出降低的溶胀行为和更长的降解时间，这使得它们适用于目前可用的组织密封剂产品可能被禁止的止血应用。

2. 发明申请

WO2011011347A2 FUNCTIONALIZATION OF SILK MATERIAL BY AVIDIN-BIOTIN INTERACTION 审中-公开
标题翻译：通过AVIDIN-BIOTIN相互作用对丝素材料的功能化
公开(公告)号：WO2011011347A2
公开(公告)日：2011-01-27
申请号：PCT/US2010/042502
申请日：2010-07-20
申请人： TRUSTEES OF TUFTS COLLEGE , KAPLAN, David L. , WANG, Xiaoqin , SERBAN, Monica A.
发明人： KAPLAN, David L. , WANG, Xiaoqin , SERBAN, Monica A.
IPC分类号： C07K14/435 , C07K19/00 , A61K47/48
CPC分类号： C07K14/43586 , A61K47/64 , A61K47/6903 , A61K47/6921
摘要： The present invention provides for compositions and methods of linking silk fibroin to active agents through the specific interaction between avidin and biotin, providing for functionalization of silk-based protein biomaterials. An avidin- or biotin-modified silk is a biomaterial platform for functionalization with a variety of correspondingly linked active agents, such as antibodies and growth factors. A variety of functionalized silk materials, such as silk hydrogel, silk micro/nanoparticles and silk films, can be prepared by the methods of the present invention. The functionalization strategies of the present invention are relatively easy, fast and feasible, and are thus useful in many biomedical applications.
摘要翻译：本发明提供通过抗生物素蛋白和生物素之间的特异性相互作用将丝素蛋白与活性剂连接的组合物和方法，提供了基于丝的蛋白质生物材料的功能化。抗生物素蛋白或生物素修饰的丝是用于与多种相应连接的活性剂如抗体和生长因子进行功能化的生物材料平台。可以通过本发明的方法制备各种功能性丝绸材料，例如丝素水凝胶，丝微/纳米颗粒和丝膜。本发明的功能化策略相对容易，快速和可行，因此在许多生物医学应用中是有用的。

3. 发明申请

WO2010126640A2 NANOIMPRINTING OF SILK FIBROIN STRUCTURES FOR BIOMEDICAL AND BIOPHOTONIC APPLICATIONS 审中-公开
标题翻译：用于生物医学和生物医学应用的丝素纤维结构的纳米生物
公开(公告)号：WO2010126640A2
公开(公告)日：2010-11-04
申请号：PCT/US2010/024004
申请日：2010-02-12
申请人： TRUSTEES OF TUFTS COLLEGE , AMSDEN, Jason J. , KAPLAN, David L. , OMENETTO, Fiorenzo
发明人： AMSDEN, Jason J. , KAPLAN, David L. , OMENETTO, Fiorenzo
IPC分类号： B82B3/00 , B29C59/02 , B29D7/01
CPC分类号： A61K9/7007 , A61K9/70 , A61K41/00 , A61K47/42 , B82Y10/00 , B82Y20/00 , B82Y30/00 , B82Y40/00 , G01N21/4788 , G01N21/774 , G01N2021/7776 , G02B5/1809 , G02B5/1847 , G02B6/02061 , G02B6/1225 , G02B6/262 , G03F7/0002 , Y10T428/24479
摘要： The present invention provides for photonic nanoimprinted silk fibroin-based materials and methods for making same, comprising embossing silk fibroin-based films with photonic nanometer scale patterns. In addition, the invention provides for processes by which the silk fibroin-based films can be nanoimprinted at room temperature, by locally decreasing the glass transition temperature of the silk film. Such nanoimprinting process increases high throughput and improves potential for incorporation of silk-based photonics into biomedical and other optical devices.
摘要翻译：本发明提供了基于光子纳米压印的丝素蛋白的材料及其制备方法，其包括用丝光纳米尺度图案压花丝素蛋白基膜。此外，本发明提供了通过局部降低丝膜的玻璃化转变温度，丝素蛋白基膜可以在室温下进行纳米压印的方法。这种纳米压印方法增加了高通量并提高了将基于丝的光子学结合到生物医学和其它光学器件中的潜力。

4. 发明申请

WO2010042798A2 MODIFIED SILK FILMS CONTAINING GLYCEROL 审中-公开
标题翻译：包含甘油的改性丝绸膜
公开(公告)号：WO2010042798A2
公开(公告)日：2010-04-15
申请号：PCT/US2009/060135
申请日：2009-10-09
申请人： TRUSTEES OF TUFTS COLLEGE , LU, Shenzhou , WANG, Xiaoqin , OMENETTO, Fiorenzo , KAPLAN, David L.
发明人： LU, Shenzhou , WANG, Xiaoqin , OMENETTO, Fiorenzo , KAPLAN, David L.
IPC分类号： A61L27/36 , A61L27/54 , A61F2/02
CPC分类号： A61L27/3604 , A61L27/3804 , A61L27/50 , A61L27/54 , A61L2420/06 , B05D1/30 , B05D3/0254 , B05D3/107 , C08J3/18 , C08J5/18 , C08J2389/00 , C08K5/053 , C12N11/02 , C08L89/00
摘要： The present invention provides for compositions and methods for preparing aqueous insoluble, ductile, flexible silk fibroin films. The silk films comprise silk fibroin and about 10% to about 50% (w/w) glycerol, and are prepared by entirely aqueous processes. The ductile silk film may be further treated by extracting the glycerol from and re-drying the silk film. Active agents may be embedded in or deposited on the glycerol modified silk film for a variety of medical applications. The films may be shaped into 3-dimentional structures, or placed on support surfaces as labels or coatings. The glycerol modified silk films of the present invention are useful in variety of applications such as tissue engineering, medical devices or implants, drug delivery, and edible pharmaceutical or food labels.
摘要翻译：本发明提供了用于制备水不溶性，可延展的柔性丝心蛋白膜的组合物和方法。丝膜包含丝素蛋白和约10％至约50％（w / w）的甘油，并且通过完全含水方法制备。可以通过从丝膜中提取甘油并再次干燥来进一步处理可延展丝膜。活性剂可嵌入或沉积在甘油改性的丝膜上用于各种医学应用。薄膜可以成型为三维结构，或者作为标签或涂层放置在支撑表面上。本发明的甘油改性的丝膜可用于多种应用，例如组织工程，医疗装置或植入物，药物递送和可食用的药物或食品标签。

5. 发明申请

WO2010036992A2 ACTIVE SILK MUCO-ADHESIVES, SILK ELECTROGELATION PROCESS, AND DEVICES 审中-公开
标题翻译：活性丝绸粘合剂，丝绸电镀工艺和器件
公开(公告)号：WO2010036992A2
公开(公告)日：2010-04-01
申请号：PCT/US2009/058534
申请日：2009-09-28
申请人： TRUSTEES OF TUFTS COLLEGE , BERNHARD, Nicolai N. , LO, Tim Jia-Ching , LEISK, Gary G. , KAPLAN, David L.
发明人： BERNHARD, Nicolai N. , LO, Tim Jia-Ching , LEISK, Gary G. , KAPLAN, David L.
IPC分类号： A61L27/36 , A61F2/02
CPC分类号： H01L41/193 , A61L27/227 , A61L27/34 , A61L27/3604 , A61L27/38 , A61L27/52 , C08L89/00
摘要： The present invention provides for compositions, methods and devices for rapidly converting silk fibroin solution into a silk fibroin gel using direct application of voltage, in a process called electrogelation. The silk fibroin gel may be reversibly converted back to liquid form by applying reverse voltage or may be converted further to β-sheet structure by applying shear force or other treatments. The electrogelated silk may be used as an extracted bulk gel, spray or stream of gel for processing into materials or devices, or may be used as silk gel coating to devices. Active agents may be embedded in the silk gel for a variety of medical applications. The electrogelated silk exists as a piezoelectric silk material comprising a mixture of silk fibroin proteins having silk I conformation and silk β-sheet structure. Silk electrogelation process of the present invention is useful in variety of applications such as tissue engineering, medical device or implants, drug delivery, soft robotics or motion associated technology.
摘要翻译：本发明提供了用于在称为电凝胶的过程中使用电压直接施加将丝素蛋白溶液迅速转化为丝素蛋白凝胶的组合物，方法和装置。丝素蛋白凝胶可以通过施加反向电压而可逆地转化为液体形式，或者可以通过施加剪切力或其他处理而进一步转化为β-折叠结构。电凝胶丝可以用作提取的批量凝胶，用于加工成材料或装置的凝胶，喷雾或凝胶流，或者可以用作装置的丝胶涂层。活性剂可嵌入蚕丝凝胶中用于各种医疗应用。电凝胶丝作为压电丝材料存在，所述压电丝材料包含具有丝状I构象和丝绸β-折叠结构的丝素蛋白的混合物。本发明的丝绸电凝胶过程可用于各种应用，例如组织工程，医疗装置或植入物，药物输送，软机器人或运动相关技术。

6. 发明申请

WO2011026101A2 SILK TRANSISTOR DEVICES 审中-公开
标题翻译：丝绸晶体管器件
公开(公告)号：WO2011026101A2
公开(公告)日：2011-03-03
申请号：PCT/US2010/047307
申请日：2010-08-31
申请人： TRUSTEES OF TUFTS COLLEGE , OMENETTO, Fiorenzo , KAPLAN, David L. , AMSDEN, Jason , CAPELLI, Raffaella , TOFFANIN, Stefano , BENFENATI, Valentina , MUCCINI, Michele , ZAMBONI, Roberto
发明人： OMENETTO, Fiorenzo , KAPLAN, David L. , AMSDEN, Jason , CAPELLI, Raffaella , TOFFANIN, Stefano , BENFENATI, Valentina , MUCCINI, Michele , ZAMBONI, Roberto
IPC分类号： H01L51/10 , H01L51/30
CPC分类号： H01L51/0093 , B82Y5/00 , B82Y10/00 , C07K14/43586 , G01N33/502 , H01L51/0036 , H01L51/0053 , H01L51/052 , H01L51/0545 , H01L51/0562 , H01L51/0566 , H01L51/5296
摘要： The invention relates to ecosustainable and biocompatible, low cost, ambient friendly electronic and optoelectronic devices, such as transistors and light-emitting transistors, made with silk fibroin or blended with other biopolymers, methods for fabrication and methods of using the silk-based electronics and optoelectronics. The silk-based electronics and optoelectronics can be implanted in vivo and in vitro for biomedical applications, such as for drug discovery or drug screening assays and devices. The silk-based devices may be used in the food industry and embedded in packaging for tracking and sensing, for security purposes or exploited as disposable not harmful for the environment efficient general electronic and optoelectronic devices.
摘要翻译：本发明涉及用丝素蛋白或与其他生物聚合物共混制备的生态可持续和生物相容性，低成本，环境友好的电子和光电子器件，例如晶体管和发光晶体管，制造方法和方法使用丝绸电子和光电子。基于丝绸的电子器件和光电子可以体外植入体内用于生物医学应用，例如用于药物发现或药物筛选测定和装置。基于丝绸的设备可用于食品工业，并嵌入包装中用于跟踪和感测，出于安全目的或作为一次性使用，对环境无害，对高效的一般电子和光电子设备无害。

7. 发明申请

WO2009100280A2 3-DIMENSIONAL SILK HYDROXYAPATITE COMPOSITIONS 审中-公开
标题翻译：三维丝羟基磷灰石组合物
公开(公告)号：WO2009100280A2
公开(公告)日：2009-08-13
申请号：PCT/US2009/033309
申请日：2009-02-06
申请人： TRUSTEES OF TUFTS COLLEGE , KAPLAN, David L. , KIM, Hyeon Joo , KUGEL, Gerard
发明人： KAPLAN, David L. , KIM, Hyeon Joo , KUGEL, Gerard
IPC分类号： A61L27/14 , A61L27/12 , A61L27/54 , A61F2/28
CPC分类号： A61F2/2846 , A61F2002/2817 , A61F2310/00293 , A61F2310/00365 , A61L27/46 , A61L27/54 , A61L2300/414 , A61L2300/602 , A61L2300/64 , A61L2430/02 , C08L89/00
摘要： Described herein are methods and compositions comprising a mixture of silk polymer and hydroxyapatite. The methods described herein can be used to prepare a mixture of silk polymer and hydroxyapatite and further provide mixtures that can be molded into a desired shape. Also encompassed herein are compositions comprising a mixture of silk polymer and hydroxyapatite having a desired shape, which can further be implanted, for example, to facilitate bone healing or tooth structure or support. Such compositions can also include agents, such as therapeutic agents, or cells.
摘要翻译：本文描述了包含丝聚合物和羟基磷灰石的混合物的方法和组合物。本文所述的方法可用于制备丝聚合物和羟基磷灰石的混合物，并进一步提供可被模制成期望形状的混合物。本文还涵盖包含具有期望形状的丝聚合物和羟基磷灰石的混合物的组合物，其可以进一步植入以例如促进骨愈合或牙齿结构或支持物。这样的组合物还可以包括药剂，例如治疗剂或细胞。

8. 发明申请

WO2011005381A2 VORTEX-INDUCED SILK FIBROIN GELATION FOR ENCAPSULATION AND DELIVERY 审中-公开
标题翻译： VORTEX诱导的丝状纤维素凝胶用于包扎和递送
公开(公告)号：WO2011005381A2
公开(公告)日：2011-01-13
申请号：PCT/US2010/036841
申请日：2010-06-01
申请人： TRUSTEES OF TUFTS COLLEGE , KAPLAN, David L. , YUCEL, Tuna
发明人： KAPLAN, David L. , YUCEL, Tuna
IPC分类号： A61K35/64 , A61K9/06 , A61K9/48 , A61K9/20
CPC分类号： A61K9/5052 , A61K9/0024 , A61K9/06 , A61K9/5089 , A61K38/00 , A61K47/42
摘要： The present invention provided for a novel process of forming silk fibroin gels, and controlling the rate of β-sheet formation and resulting hydrogelation kinetics, by vortex treatment of silk fibroin solution. In addition, the vortex treatment of the present invention provides a silk fibroin gel that may be reversibly shear-thinned, enabling the use of these approach for precise control of silk self-assembly, both spatially and temporally. Active agents, including biological materials, viable cells or therapeutic agents, can be encapsulated in the hydrogels formed from the processes, and be used as delivery vehicles. Hence, the present invention provide for methods for silk fibroin gelation that are useful for biotechnological applications such as encapsulation and delivery of active agents, cells, and bioactive molecules.
摘要翻译：本发明提供丝状蛋白凝胶形成新方法，通过涡旋处理丝素蛋白溶液来控制ß片形成速率和所得水凝胶动力学。此外，本发明的涡流处理提供了可逆地剪切变薄的丝素蛋白凝胶，使得能够在空间和时间上精确地控制丝自组装的这些方法。包括生物材料，活细胞或治疗剂在内的活性剂可以包封在由该方法形成的水凝胶中，并用作递送载体。因此，本发明提供丝素蛋白凝胶化方法，其可用于生物技术应用如活性剂，细胞和生物活性分子的包封和递送。

9. 发明申请

WO2010065957A2 VASCULARIZED LIVING SKIN CONSTRUCTS AND METHODS OF USE THEREOF 审中-公开
标题翻译：血管活性皮肤结构及其使用方法
公开(公告)号：WO2010065957A2
公开(公告)日：2010-06-10
申请号：PCT/US2009/067006
申请日：2009-12-07
申请人： TRUSTEES OF TUFTS COLLEGE , THE CHARLES STARK DRAPER LABORATORY, INC. , KAPLAN, David L. , HERMAN, Ira M. , BORENSTEIN, Jeffrey T. , GARLICK, Jonathan
发明人： KAPLAN, David L. , HERMAN, Ira M. , BORENSTEIN, Jeffrey T. , GARLICK, Jonathan
IPC分类号： C12N11/02 , C12N5/071 , A61L27/56
CPC分类号： A61L27/60 , A61L27/3604 , A61L27/38
摘要： While several devices and living skin substitutes have been developed over the past few years, none possess an integrated vasculature. Accordingly, the invention described herein provides, in part, controllable, three-dimensional human skin equivalents constructed using biodegradable microfluidic systems that encompass a variety of properties, including biodegradeability, bioactivity and full functionality, and a complete microcirculation.
摘要翻译：尽管过去几年已开发出几种装置和活体皮肤替代品，但没有一种具有整合的脉管系统。因此，本文所述的本发明部分地提供了使用可生物降解的微流体系统构建的可控制的三维人类皮肤等效物，其包含多种性质，包括生物降解性，生物活性和全部功能性以及完整的微循环。

10. 发明申请

WO2008106485A2 TISSUE-ENGINEERED SILK ORGANS 审中-公开
标题翻译：组织工程丝绸机构
公开(公告)号：WO2008106485A2
公开(公告)日：2008-09-04
申请号：PCT/US2008/055072
申请日：2008-02-27
申请人： TRUSTEES OF TUFTS COLLEGE , KAPLAN, David L. , OMENETTO, Fiorenzo , MARCHANT, Jeffrey , PANJWANI, Noorjahan , LAWRENCE, Brian
发明人： KAPLAN, David L. , OMENETTO, Fiorenzo , MARCHANT, Jeffrey , PANJWANI, Noorjahan , LAWRENCE, Brian
IPC分类号： C12N5/06 , A61L27/38
CPC分类号： A61L27/3604 , A61L27/225 , A61L27/227 , A61L27/3804 , A61L27/3839 , A61L27/3891 , A61L27/56 , A61L2300/412 , C12N5/0068 , C12N5/0621 , C12N2533/50 , G01N33/5044
摘要： This invention relates to a lamellae tissue layer, comprising a grooved silk fibroin substrate comprising tissue-specific cells. The silk fibroin substrates provides an excellent means of controlling and culturing cell and extracellular matrix development. A multitude of lamellae tissue layers can be used to create a tissue-engineered organ, such as a tissue-engineered cornea. The tissue-engineered organ is non-immunogenic and biocompatible.
摘要翻译：本发明涉及一种薄片组织层，其包括含有组织特异性细胞的开槽丝素蛋白底物。丝素蛋白底物提供了控制和培养细胞和细胞外基质发育的极好手段。可以使用多个薄片组织层来产生组织工程化器官，例如组织工程角膜。组织工程化器官是非免疫原性和生物相容性的。

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