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61. 发明授权

US06840962B1 Tissue engineered tendons and ligaments 失效
标题翻译：组织工程肌腱和韧带
公开(公告)号：US06840962B1
公开(公告)日：2005-01-11
申请号：US09670051
申请日：2000-09-25
申请人： Charles A. Vacanti , Yi Lin Cao , Robert S. Langer , Joseph P. Vacanti , Keith Paige , Joseph Upton
发明人： Charles A. Vacanti , Yi Lin Cao , Robert S. Langer , Joseph P. Vacanti , Keith Paige , Joseph Upton
IPC分类号： A61F2/08 , A61L27/18 , A61L27/38 , A61L27/58 , A61F2/02
CPC分类号： A61L27/3804 , A61F2/08 , A61L27/18 , A61L27/3604 , A61L27/3662 , A61L27/3817 , A61L27/3843 , A61L27/386 , A61L27/58 , A61L2430/10 , C08L67/04
摘要： Connective tissue, including neo-tendons and ligaments, has been constructed using biodegradable synthetic scaffolds seeded with tenocytes. The scaffolds are preferably formed from biodegradable fibers formed of a polymer such as polyglycolic acid-polylactic acid copolymers, and seeded with cells isolated from autologous tendon or ligament by means of enzymatic digestion or direct seeding into tissue culture dishes from explants. The cell polymer constructs are then surgically transplanted to replace missing segments of functioning tendon or ligament.
摘要翻译：结缔组织，包括新肌腱和韧带，已经使用可生物降解的合成支架被种植有腱鞘细胞。支架优选由聚合物如聚乙醇酸 - 聚乳酸共聚物形成的可生物降解的纤维形成，并通过酶切消化或直接接种到外植体的组织培养皿中，从自体肌腱或韧带分离的细胞接种。然后手术移植细胞聚合物构建体以代替功能性肌腱或韧带的缺失部分。

62. 发明授权

US06348069B1 Engineering of strong, pliable tissues 有权
标题翻译：坚强，柔韧的组织工程
公开(公告)号：US06348069B1
公开(公告)日：2002-02-19
申请号：US09185360
申请日：1998-11-03
申请人： Joseph P. Vacanti , Christopher K. Breuer , Beverly E. Chaignaud , Toshiraru Shin'oka
发明人： Joseph P. Vacanti , Christopher K. Breuer , Beverly E. Chaignaud , Toshiraru Shin'oka
IPC分类号： A61F202
CPC分类号： A61L27/3886 , A61F2/2415 , A61L27/18 , A61L27/3633 , A61L27/3645 , A61L27/3804 , A61L27/3843 , A61L27/507 , A61L27/58 , C08L67/04
摘要： It has been discovered that improved yields of engineered tissue following implantation, and engineered tissue having enhanced mechanical strength and flexibility or pliability, can be obtained by implantation, preferably subcutaneously, of a fibrous polymeric matrix for a period of time sufficient to obtain ingrowth of fibrous tissue and/or blood vessels, which is the removed for subsequent implantation at the site where the implant is desired. The matrix is optionally seeded prior to the first implantation, after ingrowth of the fibrous tissue, or at the time of reimplantation. The time required for fibrous ingrowth typically ranges from days to weeks. The method is particularly useful in making valves and tubular structures, especially heart valves and blood vessels.
摘要翻译：已经发现，通过植入（优选皮下）纤维聚合物基质可以获得植入后工程化组织的提高的产率和具有增强的机械强度和柔韧性或柔韧性的工程组织，持续足以获得纤维素向内生长的时间组织和/或血管，其被移除以用于在期望植入物的位置的随后植入。任选地在第一次植入之前，在纤维组织的内生之后，或在再植入时，将基质种植。纤维内生所需的时间通常在几天到几周。该方法特别适用于制造阀和管状结构，特别是心脏瓣膜和血管。

63. 发明授权

US06281015B1 Localized delivery of factors enhancing survival of transplanted cells 失效
标题翻译：移植细胞存活的因子的局部递送
公开(公告)号：US06281015B1
公开(公告)日：2001-08-28
申请号：US08358235
申请日：1994-12-16
申请人： David J. Mooney , Robert S. Langer , Joseph P. Vacanti
发明人： David J. Mooney , Robert S. Langer , Joseph P. Vacanti
IPC分类号： C12N500
CPC分类号： A61K9/0024 , A61K35/407 , A61K38/1808 , C12N5/0075 , C12N5/067 , C12N2501/11 , C12N2531/00 , C12N2533/40
摘要： Growth factors and/or angiogenic factors are administered in combination with dissociated cells to be transplanted, preferably in microspheres with the cells on or in a polymeric matrix, to enhance survival and proliferation of the transplanted cells. Examples demonstrate that epidermal growth factor (EGF) was incorporated into microspheres fabricated from a copolymer of lactic and glycolic acid using a double emulsion technique, the incorporated EGF was steadily released over one month in vitro, and it remained biologically active, as determined by its ability to stimulate DNA synthesis, division, and long-term survival of cultured hepatocytes. EGF-containing microspheres were mixed with a suspension of hepatocytes, seeded onto porous sponges, and implanted into the mesentery of two groups of Lewis rats, to demonstrate efficacy in vivo. Two weeks after implantation in PCS animals, devices which included EGF-containing microspheres showed a two-fold increase in the number of engrafted hepatocytes, as compared to implants which received blank microspheres.
摘要翻译：生长因子和/或血管生成因子与待移植的解离的细胞组合施用，优选在具有在聚合物基质上或聚合物基质中的细胞的微球体中，以增强移植细胞的存活和增殖。实例表明，使用双重乳液技术将表皮生长因子（EGF）掺入由乳酸和乙醇酸共聚物制成的微球体中，结合的EGF在体外稳定释放一个月，并且其保持生物活性，如刺激培养的肝细胞的DNA合成，分裂和长期存活的能力。将含EGF的微球与肝细胞悬浮液混合，接种到多孔海绵上，并植入两组Lewis大鼠的肠系膜，以体现体内效力。植入PCS动物两周后，与含有空白微球的植入物相比，包含含EGF的微球的装置显示出移植肝细胞数量增加了两倍。

64. 发明授权

US06176874B1 Vascularized tissue regeneration matrices formed by solid free form fabrication techniques 失效
标题翻译：由固体自由形式制造技术形成的血管化组织再生基质
公开(公告)号：US06176874B1
公开(公告)日：2001-01-23
申请号：US08477226
申请日：1995-06-07
申请人： Joseph P. Vacanti , Linda G. Cima , Michael J. Cima
发明人： Joseph P. Vacanti , Linda G. Cima , Michael J. Cima
IPC分类号： A61F200
CPC分类号： A61F2/105 , A61F2/022 , A61F2/28 , A61F2/30756 , A61F2/3094 , A61F2002/0086 , A61F2002/009 , A61F2002/30011 , A61F2002/30032 , A61F2002/30034 , A61F2002/30062 , A61F2002/30199 , A61F2002/3028 , A61F2002/30677 , A61F2002/3093 , A61F2002/30932 , A61F2002/30962 , A61F2210/0004 , A61F2230/0063 , A61F2240/001 , A61F2250/0023 , A61F2250/003 , A61F2250/0031 , A61F2250/0067 , A61L27/3808 , A61L27/40 , A61L27/56 , A61L27/60 , B29C64/135 , B29C64/165 , B29K2995/0064 , B33Y10/00 , B33Y30/00 , B33Y80/00 , Y10S623/901 , A61L27/38
摘要： Solid free-form fabrication (SFF) methods are used to manufacture devices for allowing tissue regeneration and for seeding and implanting cells to form organ and structural components, which can additionally provide controlled release of bioactive agents, wherein the matrix is characterized by a network of lumens functionally equivalent to the naturally occurring vasculature of the tissue formed by the implanted cells, and which can be lined with endothelial cells and coupled to blood vessels at the time of implantation to form a vascular network throughout the matrix. The SFF methods can be adapted for use with a variety of polymeric, inorganic and composite materials to create structures with defined compositions, strengths, and densities, using computer aided design (CAD). Examples of SFF methods include stereo-lithography (SLA), selective laser sintering (SLS), ballistic particle manufacturing (BPM), fusion deposition modeling (FDM), and three dimensional printing (3DP).
摘要翻译：固体自由形式制造（SFF）方法用于制造用于允许组织再生和用于种植和植入细胞以形成器官和结构组分的装置，其可另外提供生物活性剂的受控释放，其中所述基质的特征在于：流体功能上等同于由植入的细胞形成的组织的天然存在的脉管系统，并且其可以在植入时与内皮细胞排列并耦合到血管，以在整个基质中形成血管网络。 SFF方法可以适用于各种聚合物，无机和复合材料，以使用计算机辅助设计（CAD）创建具有确定的组成，强度和密度的结构。SFF方法的实例包括立体光刻（SLA），选择性激光烧结（SLS），弹道粒子制造（BPM），熔融沉积建模（FDM）和三维打印（3DP）。

65. 发明授权

US6027744A Guided development and support of hydrogel-cell compositions 失效
标题翻译：指导开发和支持水凝胶细胞组合物
公开(公告)号：US6027744A
公开(公告)日：2000-02-22
申请号：US66038
申请日：1998-04-24
申请人： Charles A. Vacanti , Joseph P. Vacanti
发明人： Charles A. Vacanti , Joseph P. Vacanti
IPC分类号： A61F2/00 , A61F2/02 , A61F2/28 , A61F2/30 , A61L27/12 , A61L27/18 , A61L27/38 , A61L27/52
CPC分类号： A61L27/12 , A61F2/28 , A61F2/30756 , A61L27/18 , A61L27/38 , A61L27/52 , A61F2002/30062 , A61F2002/30199 , A61F2210/0004 , A61F2230/0063 , A61F2310/00293
摘要： The invention features a method for generating new tissue, the method including: obtaining a liquid hydrogel-cell composition including a hydrogel and tissue precursor cells; delivering the liquid hydrogel-cell composition into a permeable, biocompatible support structure; and allowing the liquid hydrogel-cell composition to solidify within the support structure and the tissue precursor cells to grow and generate new tissue. The invention also features a tissue forming structure including: a permeable, biocompatible support structure having a predetermined shape that corresponds to the shape of desired tissue; and a hydrogel-cell composition at least partially filling the support structure, wherein the hydrogel-cell composition comprises a hydrogel and tissue precursor cells.
摘要翻译：本发明的特征在于产生新组织的方法，该方法包括：获得包含水凝胶和组织前体细胞的液体水凝胶细胞组合物; 将液体水凝胶细胞组合物递送到可渗透的生物相容性支持结构中; 并允许液体水凝胶细胞组合物在支撑结构和组织前体细胞内固化生长并产生新的组织。本发明还具有一种组织形成结构，其包括：具有对应于所需组织形状的预定形状的可渗透的生物相容性支撑结构; 以及至少部分填充所述支持结构的水凝胶细胞组合物，其中所述水凝胶细胞组合物包含水凝胶和组织前体细胞。

66. 发明授权

US5855610A Engineering of strong, pliable tissues 失效
公开(公告)号：US5855610A
公开(公告)日：1999-01-05
申请号：US445280
申请日：1995-05-19
申请人： Joseph P. Vacanti , Christopher K. Breuer , Beverly E. Chaignaud , Toshiraru Shin'oka
发明人： Joseph P. Vacanti , Christopher K. Breuer , Beverly E. Chaignaud , Toshiraru Shin'oka
IPC分类号： A61F2/24 , A61L27/18 , A61L27/38 , A61L27/50 , A61F2/02
CPC分类号： A61L27/3886 , A61L27/18 , A61L27/3633 , A61L27/3645 , A61L27/3804 , A61L27/3843 , A61L27/507 , A61F2/2415
摘要： It has been discovered that improved yields of engineered tissue following implantation, and engineered tissue having enhanced mechanical strength and flexibility or pliability, can be obtained by implantation, preferably subcutaneously, of a fibrous polymeric matrix for a period of time sufficient to obtain ingrowth of fibrous tissue and/or blood vessels, which is the removed for subsequent implantation at the site where the implant is desired. The matrix is optionally seeded prior to the first implantation, after ingrowth of the fibrous tissue, or at the time of reimplantation. The time required for fibrous ingrowth typically ranges from days to weeks. The method is particularly useful in making valves and tubular structures, especially heart valves and blood vessels.

67. 发明授权

US5736372A Biodegradable synthetic polymeric fibrous matrix containing chondrocyte for in vivo production of a cartilaginous structure 失效
标题翻译：含有软骨细胞的可生物降解的合成聚合物纤维基质用于体内产生软骨结构
公开(公告)号：US5736372A
公开(公告)日：1998-04-07
申请号：US509952
申请日：1990-04-16
申请人： Joseph P. Vacanti , Charles A. Vacanti , Robert S. Langer
发明人： Joseph P. Vacanti , Charles A. Vacanti , Robert S. Langer
IPC分类号： A61F2/02 , A61F2/06 , A61F2/30 , A61K35/12 , A61L27/38 , A61L27/60 , C12N5/00 , C12N5/077 , C12N11/08 , A61F2/28 , A61F2/18
CPC分类号： C12N5/0655 , A61F2/02 , A61F2/062 , A61L27/38 , A61L27/60 , C12N5/0068 , A61F2/30756 , A61F2002/30062 , A61F2210/0004 , A61K35/12 , A61L2430/06 , C12N2533/18 , C12N2533/30 , C12N2533/40
摘要： Methods and artificial matrices for the growth and implantation of cartilaginous structures and surfaces and bone are disclosed. In the preferred embodiments, chondrocytes are grown on biodegradable, biocompatible fibrous polymeric matrices. Optionally, the cells are proliferated in vitro until an adequate cell volume and density has developed for the cells to survive and proliferate in vivo. One advantage of the matrices is that they can be cast or molded into a desired shape, on an individual basis, so that the final product closely resembles a patient's own ear or nose. Alternatively, flexible matrices can be used which can be manipulated at the time of implantation, as in a joint, followed by remodeling through cell growth and proliferation in vivo. The cultured cells can also be maintained on the matrix in a nutrient media for production of bioactive molecules such as angiogenesis inhibiting factor. Examples are provided showing the growth of hyaline cartilage for joint relinings, the growth of elastic cartilage for plastic or reconstructive replacement of cartilage structures, and repair of large bone defects.
摘要翻译：公开了用于生长和植入软骨结构和表面和骨的方法和人造基质。在优选的实施方案中，软骨细胞生长在可生物降解的生物相容的纤维聚合物基质上。任选地，细胞在体外增殖，直至形成足够的细胞体积和密度，使细胞在体内存活和增殖。基质的一个优点是它们可以在个体的基础上铸造或模制成所需的形状，使得最终产品非常类似于患者自己的耳朵或鼻子。或者，可以使用可在植入时操作的柔性基质，如在关节中，随后通过体内细胞生长和增殖重塑。培养的细胞也可以在营养培养基中维持在基质上，用于生产生物活性分子如血管生成抑制因子。提供了示例，其显示用于联合放置的透明软骨的生长，塑料的弹性软骨的生长或软骨结构的重建置换以及大的骨缺损的修复。

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