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11. 发明申请

WO2010057142A2 SURFACE MODIFICATION OF SILK FIBROIN MATRICES WITH POLY(ETHYLENE GLYCOL) USEFUL AS ANTI ADHESION BARRIERS AND ANTI THROMBOTIC MATERIALS 审中-公开
标题翻译：用聚（乙二醇）作为抗粘连阻挡层和抗血栓材料表面改性丝素蛋白基质
公开(公告)号：WO2010057142A2
公开(公告)日：2010-05-20
申请号：PCT/US2009/064673
申请日：2009-11-17
申请人： TRUSTEES OF TUFTS COLLEGE , VEPARI, Charu P. , KAPLAN, David L.
发明人： VEPARI, Charu P. , KAPLAN, David L.
IPC分类号： A61L33/00 , A61L27/36 , A61L27/54 , A61P7/00
CPC分类号： A61L31/005 , A61L31/10 , A61L33/068 , C08L71/02
摘要： The present invention provides compositions and methods for the production of silk fibroin matrices surface-PEGylated on one or more surfaces. Such surface-PEGylated silk fibroin matrices can be used in biomedical applications, such as anti-adhesive and anti-thrombosis materials. Silk matrices may be surface-PEGylated, for example, by a reaction with a functional group-activated PEG. Controlling the degree of PEGylation on surface of silk fibroin matrix can regulate both the degradation rate of the silk matrix, and the differentiated adhesion of cells or differentiated adsorption of proteins on the surface of the silk matrix. The present invention also provides for silk fibroin matrices having one or more surfaces possessing differentiated adhesion properties, which allows for tissue integration on the adherent side and inhibition of tissue adhesion to the opposing tissues or organs. Embedding active agents in silk fibroin matrices provides more benefits, such as promoting tissue ingrowth on the adherent side of the matrix.
摘要翻译：本发明提供了用于生产在一个或多个表面上表面聚乙二醇化的丝素蛋白基质的组合物和方法。这种表面聚乙二醇化丝素蛋白基质可用于生物医学应用，例如抗粘连和抗血栓形成材料。例如，丝绸基质可以通过与官能团活化的PEG反应而表面聚乙二醇化。通过控制丝素蛋白基质表面的聚乙二醇化程度，可以调控丝素基质的降解速率，以及细胞的分化粘附或蛋白质在丝基质表面的差异化吸附。本发明还提供具有一个或多个具有不同粘附性质的表面的丝素蛋白基质，其允许粘附侧上的组织整合和抑制组织粘附到相对的组织或器官上。将活性剂包埋在丝素蛋白基质中提供了更多益处，例如促进基质粘附侧上的组织向内生长。

12. 发明申请

WO2009023615A1 TUBULAR SILK COMPOSITIONS AND METHODS OF USE THEREOF 审中-公开
标题翻译：管状丝素组合物及其使用方法
公开(公告)号：WO2009023615A1
公开(公告)日：2009-02-19
申请号：PCT/US2008/072742
申请日：2008-08-11
申请人： TRUSTEES OF TUFTS COLLEGE , LOVETT, Michael L. , WANG, Xianyan , CANNIZZARO, Christopher , VUNJAK-NOVAKOVIC, Gordana , KAPLAN, David L.
发明人： LOVETT, Michael L. , WANG, Xianyan , CANNIZZARO, Christopher , VUNJAK-NOVAKOVIC, Gordana , KAPLAN, David L.
IPC分类号： A61F2/08 , A61L27/22
CPC分类号： A61L27/227 , A61F2/07 , A61F2/08 , A61F2/82 , A61L27/26 , A61L27/3604 , D10B2211/22 , Y10T428/13 , C08L89/00
摘要： Described are tubular silk fibroin compositions and methods for their manufacture and use. Tubular compositions as described herein can be produced in a range of high burst strengths, can easily be made in a range of inner diameters, can be derivatized with functional moieties, and can be produced in a range of permeabilities suitable for particularized uses. In one aspect, the tubular compositions can be used in the repair or replacement of damaged or diseased blood vessels, including, but not limited to vessels smaller than about 6 mm.
摘要翻译：描述的是管状丝素蛋白组合物及其制造和使用的方法。如本文所述的管状组合物可以在高爆裂强度的范围内制备，可以容易地在内径范围内制备，可以用官能部分衍生化，并且可以在适合于特定用途的渗透性范围内制备。在一个方面，管状组合物可用于修复或更换受损或患病的血管，包括但不限于小于约6mm的血管。

13. 发明申请

WO2012145739A1 COMPOSITIONS AND METHODS FOR STABILIZATION OF ACTIVE AGENTS 审中-公开
标题翻译：用于稳定活性剂的组合物和方法
公开(公告)号：WO2012145739A1
公开(公告)日：2012-10-26
申请号：PCT/US2012/034643
申请日：2012-04-23
申请人： TRUSTEES OF TUFTS COLLEGE , KAPLAN, David L. , OMENETTO, Fiorenzo
发明人： KAPLAN, David L. , OMENETTO, Fiorenzo
IPC分类号： A61K47/42 , A61K39/12 , A61J1/00 , B82Y5/00 , A61K35/76 , A61K39/00 , A61M5/00
CPC分类号： A61K39/20 , A61K9/0019 , A61K9/06 , A61K9/146 , A61K9/19 , A61K9/5026 , A61K9/5063 , A61K9/7007 , A61K38/00 , A61K39/0015 , A61K39/02 , A61K39/04 , A61K39/08 , A61K39/092 , A61K39/095 , A61K39/099 , A61K39/12 , A61K39/165 , A61K47/42 , A61K47/46 , A61K2039/5252 , A61K2039/5254 , A61K2039/6031 , A61K2039/622 , A61K2039/64 , A61K2039/70 , B82Y5/00 , C12N2760/18434 , C12N2760/18734 , C12N2770/36234 , Y02A50/388 , Y02A50/39 , Y02A50/466 , Y02A50/484
摘要： Provided herein are methods and compositions for stabilization of active agents. The active agents are distributed, mixed or embedded in a silk fibroin matrix, thereby retaining the bioactivity of the active agents upon storage and/or transportation. In some embodiments, the storage-stable vaccine-silk compositions are also provided herein.
摘要翻译：本文提供了用于稳定活性剂的方法和组合物。活性剂分布，混合或嵌入丝素蛋白基质中，从而保持活性剂在储存和/或运输过程中的生物活性。在一些实施方案中，本文还提供了储存稳定的疫苗丝组合物。

14. 发明申请

WO2012054582A2 SILK FIBROIN-BASED MICRONEEDLES AND METHODS OF MAKING THE SAME 审中-公开
标题翻译：基于丝基纤维素的麦克风及其制备方法
公开(公告)号：WO2012054582A2
公开(公告)日：2012-04-26
申请号：PCT/US2011/056856
申请日：2011-10-19
申请人： TRUSTEES OF TUFTS COLLEGE , KAPLAN, David L. , TSIORIS, Konstantinos , OMENETTO, Fiorenzo G. , PRITCHARD, Eleanor M.
发明人： KAPLAN, David L. , TSIORIS, Konstantinos , OMENETTO, Fiorenzo G. , PRITCHARD, Eleanor M.
IPC分类号： A61M37/00 , A61M5/158 , A61L27/58
CPC分类号： A61L31/125 , A61B17/205 , A61K9/0021 , A61L31/047 , A61L31/16 , A61M5/158 , A61M37/0015 , A61M2037/0046 , A61M2037/0053
摘要： A microneedle or microneedle device includes a microneedle body extending from a base to a penetrating tip formed from a silk fibroin based material, which is easy to fabricate and highly biocompatible. The microneedle device can include one or more microneedles mounted to a substrate. The silk fibroin can include active agents to be transported into or across biological barriers such as skin, tissue and cell membranes. The silk fibroin microneedles can be fully or partially biodegradable and/or bioerodible. The silk fibroin is highly stable, affords room temperature storage and is implantable. The silk fibroin structure can be modulated to control the rate of active agent delivery.
摘要翻译：微针或微针装置包括从基部延伸到由丝素蛋白基材料形成的穿透尖端的微针体，其易于制造和高度生物相容性。微针装置可以包括安装到基底的一个或多个微针。丝素蛋白可以包括被运送到生物屏障如皮肤，组织和细胞膜之中或之上的活性剂。丝素蛋白微针可以全部或部分生物降解和/或生物侵蚀。丝素蛋白高度稳定，提供室温储存并可植入。可以调节丝素蛋白结构以控制活性剂递送的速率。

15. 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。

16. 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。

17. 发明公开

EP4257202A2 INJECTABLE SILK FIBROIN PARTICLES AND USES THEREOF 审中-实审
公开(公告)号：EP4257202A2
公开(公告)日：2023-10-11
申请号：EP23168344.2
申请日：2012-11-09
申请人： Trustees of Tufts College , University of Pittsburgh - Of the Commonwealth System of Higher Education , Wake Forest University Health Services
发明人： BELLAS, Evangelia , MARRA, Kacey , RUBIN, Peter J. , KAPLAN, David L. , YOO, James J.
IPC分类号： A61P43/00
摘要： The inventions provided herein relate to compositions, methods, delivery devices and kits for repairing or augmenting a tissue in a subject. The compositions described herein are injectable such that they can be placed in a tissue to be treated with a minimally-invasive procedure (e.g., by injection) and/or be molded flexibly into a tissue void of any shape and/or size. In some embodiments, the composition described herein comprises a plurality of silk fibroin particles, which can retain their original volume within the tissue for a period of time. The compositions can be used as a filler to replace a tissue void, e.g., for tissue repair and/or augmentation, or as a scaffold to support tissue regeneration and/or reconstruction. In some embodiments, the compositions described herein can be used for soft tissue repair or augmentation.

18. 发明公开

EP4180448A1 LOW MOLECULAR WEIGHT SILK COMPOSITIONS AND STABILIZING SILK COMPOSITIONS 审中-实审
公开(公告)号：EP4180448A1
公开(公告)日：2023-05-17
申请号：EP22188893.6
申请日：2014-03-14
申请人： Trustees of Tufts College
发明人： KAPLAN, David L. , KLUGE, Jonathon A. , OMENETTO, Fiorenzo G.
IPC分类号： C07K14/435 , C07K14/50 , A61L27/36 , A61K47/42 , A61K9/19 , B01J20/24
摘要： The present disclosure provides certain silk-fibroin compositions with particular characteristics and/or properties.

19. 发明公开

EP2836236A1 METHODS AND COMPOSITIONS FOR PREPARING A SILK MICROSPHERE 无效
标题翻译：方法和组合物制作组织微球
公开(公告)号：EP2836236A1
公开(公告)日：2015-02-18
申请号：EP13775182.2
申请日：2013-04-12
申请人： Trustees Of Tufts College
发明人： KAPLAN, David L. , YUCEL, Tuna , WANG, Xiaoqin , LOVETT, Michael
IPC分类号： A61K47/42 , A61K47/30 , A61K9/16 , A61K9/14
CPC分类号： A61K9/1682 , A61K9/0019 , A61K9/1617 , A61K9/1658 , A61K31/13 , A61K47/38 , C07K16/22
摘要： Provided herein relates to methods and compositions for preparing a silk microsphere and the resulting silk microsphere. In some embodiments, the methods and compositions described herein are all aqueous, which can be used for encapsulating an active agent in a silk microsphere, while maintaining activity of the active agent during processing. In some embodiments, the resulting silk microsphere can be used for sustained delivery of an active agent encapsulated therein.

20. 发明公开

EP2474054A2 SILK TRANSISTOR DEVICES 审中-公开
标题翻译： SILK晶体管器件
公开(公告)号：EP2474054A2
公开(公告)日：2012-07-11
申请号：EP10812751.5
申请日：2010-08-31
申请人： Tufts University/Trustees of Tufts College
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.

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