Enzyme-mediated modification of fibrin for tissue engineering: fibrin formulations with peptides
    82.
    发明授权
    Enzyme-mediated modification of fibrin for tissue engineering: fibrin formulations with peptides 失效
    用于组织工程的酶介导的纤维蛋白修饰:具有肽的纤维蛋白制剂

    公开(公告)号:US07241730B2

    公开(公告)日:2007-07-10

    申请号:US10106804

    申请日:2002-03-25

    IPC分类号: A01N37/18

    摘要: Heparin-binding regions of several proteins, such as neural cell adhesion molecule, fibronectin, laminin, midkine, and anti-thrombin III have been shown to promote neurite extension on two-dimensional surfaces. The effect of heparin-binding peptides on neurite extension through three-dimensional matrices was investigated by culturing embryonic chick dorsal root ganglia (DRG) within fibrin gels containing chemically attached heparin-binding peptide (HBP). The length of neurites within fibrin gels containing cross-linked HBP was increased by more than 70% over extension through fibrin gels containing no peptide. The HBP sequence of antithrombin III was incorporated into the fibrin gel as the C-terminal domain of a bidomian, chimeric peptide; the N-terminal second domain of this peptide contained the ∀2-plasmin inhibitor substrate for Factor XIIIa. Factor XIIIa, a transglutaminase, was used to chemically attach the HBP-containing chimeric peptide to the fibrin gels during polymerization. The amount of HBP cross-linked into the fibrin gels was determined, after degradation by plasmin using gel permeation chromatography, to be approximately 8 moles of peptide per mole fibrinogen. A peptide (HBP), where the cross-linking glutamine was replaced with glycine, showed no increase in extension in comparison with fibrin gels. The additional of heparin to the gel percursors resulted in no increase in neurite extension in comparison with fibrin gels. HBPs promote neurite extension by binding to cell surface proteoglycans on the DRG.

    摘要翻译: 几种蛋白质的肝素结合区域,例如神经细胞粘附分子,纤连蛋白,层粘连蛋白,中期因子和抗凝血酶III已被证明可促进二维表面的神经突延伸。 通过在包含化学连接的肝素结合肽(HBP)的纤维蛋白凝胶内培养胚胎小鸡背根神经节(DRG),研究肝素结合肽对通过三维基质的神经突延伸的作用。 含有交联HBP的纤维蛋白凝胶中的神经突的长度比通过不含肽的纤维蛋白凝胶延长超过70%。 抗凝血酶III的HBP序列被掺入纤维蛋白凝胶中,作为bid族嵌合肽的C-末端结构域; 该肽的N末端第二结构域含有因子XIIIa的∀2-纤溶酶抑制剂底物。 在聚合期间,使用因子XIIIa,转谷氨酰胺酶将含HBP的嵌合肽化学连接到纤维蛋白凝胶上。 在使用凝胶渗透色谱法的纤溶酶降解之后,测定交联到纤维蛋白凝胶中的HBP的量为每摩尔纤维蛋白原约8摩尔肽。 交联谷氨酰胺被甘氨酸取代的肽(HBP)与纤维蛋白凝胶相比显示延长不增加。 与纤维蛋白凝胶相比,附加的凝胶过程中的肝素导致神经突延伸不增加。 HBP通过与DRG上的细胞表面蛋白聚糖结合来促进神经突延伸。

    Methods for stabilizing biologically active agents encapsulated in biodegradable controlled-release polymers
    85.
    发明授权
    Methods for stabilizing biologically active agents encapsulated in biodegradable controlled-release polymers 失效
    用于稳定包封在可生物降解的控释聚合物中的生物活性剂的方法

    公开(公告)号:US06743446B2

    公开(公告)日:2004-06-01

    申请号:US09738961

    申请日:2000-12-15

    IPC分类号: A61K914

    摘要: Methods for reducing or inhibiting the irreversible inactivation of water-soluble biologically active agents in biodegradable polymeric delivery systems which are designed to release such agents over a prolonged period of time, such as PLGA delivery systems are provided. The method comprises preparing a PLGA delivery systems whose microclimate, i.e. the pores where the active agent resides, uniformly or homogenously maintain a pH of between 3 and 9, preferably between 4 and 8, more preferably between 5 and 7.5 during biodegradation. Depending on the size of the delivery system, and the initial bulk permeability of the polymer, this result is achieved by (a) incorporating a water-soluble carrier into the delivery system, (b) incorporating a select basic additive (or antacid) into the delivery system, (c) incorporating both a water soluble carrier and a select basic additive into the delivery system, (d) adding a pore forming molecule for increasing the rate of release of low molecular weight monomers and oligomers into the delivery system, (e) using a PLGA polymer with reduced glycolide content, i.e. PLGA with from 100% to 75% lactide and 0 to 25% glycolide) (f) using a microencapsulation method that yields a more extensive pore-network, e.g. oil-in-oil emulsion-solvent extraction as opposed to water-in-oil-in water-solvent evaporation method, and (g) combinations thereof.

    摘要翻译: 提供了用于减少或抑制在可生物降解的聚合物递送系统中的水溶性生物活性剂的不可逆失活的方法,其被设计为在长时间内释放这些试剂,例如PLGA递送系统。 该方法包括制备PLGA递送系统,其微生物即活性剂所在的孔在生物降解过程中均匀或均匀地保持在3至9之间,优选4至8之间,更优选5至7.5的pH。 根据输送系统的尺寸和聚合物的初始体积渗透性,该结果通过(a)将水溶性载体引入输送系统来实现,(b)将选择的碱性添加剂(或抗酸剂)掺入 递送系统,(c)将水溶性载体和选择性碱性添加剂并入输送系统中,(d)添加成孔分子,以将低分子量单体和低聚物的释放速率提高到递送系统中( e)使用具有降低的乙交酯含量的PLGA聚合物,即具有100%至75%丙交酯和0至25%乙交酯的PLGA)(f)使用产生更广泛孔隙网络的微胶囊化方法,例如 油包水乳液 - 溶剂萃取相对于水包油型水溶剂蒸发法,和(g)它们的组合。

    Multifunctional organic polymers
    87.
    发明授权
    Multifunctional organic polymers 失效
    多功能有机聚合物

    公开(公告)号:US5462990A

    公开(公告)日:1995-10-31

    申请号:US132507

    申请日:1993-10-05

    摘要: Described herein is a multi-functional polymeric material for use in inhibiting adhesion and immune recognition between cells and cells, cells and tissues, and tissues and tissues. One component of the polymeric material adsorbs well to cells or tissue, and the other component of the polymeric material does not adsorb well to tissues. A water-soluble polymer that does not bear charge (polynonion) is used as the non-binding component, and a water soluble polymer that is positively charged at physiological pH (polycation) is used as the tissue binding component. When the bi-functional polymeric material contacts a tissue, the tissue-binding component binds and thus immobilizes the attached non-binding component, which will then extend generally away from the tissue surface and sterically block the attachment of other tissues. The method and compositions are useful in inhibiting formation of post-surgical adhesions, protecting damaged blood vessels from thrombosis and restenosis, and decreasing the extent of metastasis of attachment-dependent tumor cells.

    摘要翻译: 本文描述的是用于抑制细胞和细胞,细胞和组织以及组织和组织之间的粘附和免疫识别的多功能聚合物材料。 聚合物材料的一个组分很好地吸附到细胞或组织上,而聚合物材料的其它组分不能很好地吸附到组织上。 使用不带电荷的水溶性聚合物(多项式)作为非结合成分,使用在生理pH(聚阳离子)下带正电的水溶性聚合物作为组织结合成分。 当双官能聚合物材料接触组织时,组织结合组分结合并因此固定所连接的非结合组分,其然后将一般远离组织表面延伸,并空间阻断其它组织的附着。 该方法和组合物可用于抑制手术后粘连的形成,保护受损的血管免受血栓形成和再狭窄,并降低附着依赖性肿瘤细胞的转移程度。

    Drug delivery matrices to enhance wound healing
    88.
    发明授权
    Drug delivery matrices to enhance wound healing 有权
    药物递送基质以增强伤口愈合

    公开(公告)号:US08309518B2

    公开(公告)日:2012-11-13

    申请号:US12845354

    申请日:2010-07-28

    摘要: Bioactive molecules are entrapped within a matrix for the controlled delivery of these compounds for therapeutic healing applications. The matrix may be formed of natural or synthetic compounds. The primary method of entrapment of the bioactive molecule is through precipitation of the bioactive molecule during gelation of the matrix, either in vitro or in vivo. The bioactive molecule may be modified to reduce its effective solubility in the matrix to retain it more effectively within the matrix, such as through the deglycosylation of members within the cystine knot growth factor superfamily and particularly within the TGFβ superfamily. The matrix may be modified to include sites with binding affinity for different bioactive molecules, for example, for heparin binding.

    摘要翻译: 生物活性分子被包埋在基质内,用于受控递送这些化合物用于治疗性愈合应用。 基质可以由天然或合成的化合物形成。 捕获生物活性分子的主要方法是通过体外或体内在基质凝胶化过程中沉淀生物活性分子。 生物活性分子可以被修饰以降低其在基质中的有效溶解度,以便在基质内更有效地保留生物活性分子,例如通过胱氨酸结生长因子超家族内,特别是在TGF-bgr内的成员的去糖基化; 超家族 可以修饰基质以包括对不同生物活性分子具有结合亲和力的位点,例如用于肝素结合的位点。

    Methods and apparatus for selective, oxidative patterning of a surface
    89.
    发明授权
    Methods and apparatus for selective, oxidative patterning of a surface 有权
    用于表面选择性,氧化图案化的方法和装置

    公开(公告)号:US08119335B2

    公开(公告)日:2012-02-21

    申请号:US11333090

    申请日:2006-01-17

    IPC分类号: C08F2/54 C08F2/48 G03F7/00

    摘要: The present invention provides methods and apparatus for selectively patterning surfaces using radical species generated with a photocatalyst. The photocatalyst may comprise a photocatalytic semiconductor or a photosensitizer. The radical species are brought into contact with an oxidizable coating disposed on the surface, thereby locally oxidizing and selectively patterning the surface. The photocatalyst is preferably disposed on a delivery device, such as a stamp, mask, or scanning probe, that is brought into close proximity or contact with the coated surface. The photocatalyst is then excited in a manner capable of generating radical species, for example, oxygen-containing radical species, in appropriate media. It is expected that these radical species will be transferred to the coated surface along a substantially shortest distance path, thereby locally oxidizing and patterning the surface.

    摘要翻译: 本发明提供了使用由光催化剂生成的自由基物质来选择性地图案化表面的方法和装置。 光催化剂可以包含光催化半导体或光敏剂。 使自由基物质与设置在表面上的可氧化涂层接触,从而局部氧化并选择性地图案化该表面。 光催化剂优选地设置在与涂覆表面紧密接触或接触的输送装置,例如印模,掩模或扫描探针上。 然后在适当的介质中以能够产生自由基物质,例如含氧自由基物质的方式激发光催化剂。 预期这些自由基物质将沿着基本上最短的距离路径转移到涂覆的表面,从而局部氧化和图案化表面。