Biocompatibility of mannuronic acid-rich alginates
Biocompatibility of mannuronic acid-rich alginates
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DOI：
10.1016/s0142-9612(96)00204-9
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发表时间：
1997-05-01
期刊：
影响因子：
14
通讯作者：
Zimmermann, U
中科院分区：
文献类型：
--
作者：
Klock, G;Pfeffermann, A;Zimmermann, U
高纯度的海藻素制剂不含内毒素和其他有丝分裂原的有害污染物，最近通过一种新的纯化工艺（Klock等人，apple, Microbiol）。Biotechnol。， 1994, 40, 638-643)。这种纯化方案的优点是，它可以适用于海藻酸与甘露醛酸的各种比例。高甘露醛酸海藻酸盐胶囊对细胞移植和生物杂交器官具有特别的实际意义，因为富含甘露醛酸盐的海藻酸盐通常粘度较低，允许人们制作含有较高海藻酸盐含量的凝胶。这将增加它们的稳定性和降低扩散的渗透性，因此可以保护固定细胞更有效地对抗宿主免疫系统。在这里，我们报道了纯化的富含甘露醛酸的海藻酸盐（68%甘露醛酸残留物）在一系列体外和体内的生物相容性。与海藻酸盐提取物相比，纯化后的产物对小鼠淋巴细胞没有促有丝分裂活性。其内毒素含量降至溶剂水平。用这些新的纯化海藻素配方进行的动物研究表明，即使将纯化的材料（与Ba2+离子交联后）植入巨噬细胞活性升高的动物模型（糖尿病易发的BB/OK大鼠），也没有发生丝裂原诱导的异物反应。因此，具有高甘露醛酸含量的海藻酸盐胶囊可用于植入等应用。除了在治疗和生物技术中用作植入式细胞反应器外，这些纯化的海藻素在眼填充物、组织替代品、微囊化生长因子和/或白细胞介素或抗体的缓释剂型、传感器和其他侵入性医疗设备的表面涂层以及基因治疗的基因工程细胞的封装方面具有广泛的应用潜力。1997爱思唯尔科学有限公司
Highly purified algin preparations free of adverse contaminants with endotoxins and other mitogens recently became available by a new purification process (Klock et al., Appl, Microbiol. Biotechnol., 1994, 40, 638-643). An advantage of this purification protocol is that it can be applied to alginates with various ratios of mannuronic acid to guluronic acid. High mannuronic acid alginate capsules are of particular practical interest for cell transplantation and for biohybrid organs, because mannuronate-rich alginates are usually less viscous, allowing one to make gels with a higher alginate content. This will increase their stability and reduce the diffusion permeability and could therefore protect immobilized cells more efficiently against the host immune system. Here we report the biocompatibility of purified, mannuronic acid-rich alginate (68% mannuronate residues) in a series of in vitro, as well as in vivo, assays. In contrast to raw alginate extracts, the purified product showed no mitogenic activity towards murine lymphocytes in vitro. Its endotoxin content was reduced to the level of the solvent. Animal studies with these new, purified algin formulations revealed the absence of a mitogen-induced foreign body reaction, even when the purified material (after cross-linking with Ba2+ ions) is implanted into animal models with elevated macrophage activity (diabetes-prone BB/OK rat). Thus, alginate capsules with high mannuronic acid content become available for applications such as implantation. In addition to the utilization as implantable cell reactors in therapy and biotechnology, these purified algins have broad application potential as ocular fillings, tissue replacements, microencapsulated growth factors and/or interleukins or slow-release dosage forms of antibodies, surface coatings of sensors and other invasive medical devices, and in encapsulation of genetically engineered cells for gene therapy. (C) 1997 Elsevier Science Limited.