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本文荣获医院实习生、住院医师类别的SFB奖:肽生物材料在伤口愈合环境中引发适应性免疫反应。

This paper is the winner of an SFB Award in the Hospital Intern, Residency category: Peptide biomaterials raising adaptive immune responses in wound healing contexts.

作者信息

Vigneswaran Yalini, Han Huifang, De Loera Roberto, Wen Yi, Zhang Xing, Sun Tao, Mora-Solano Carolina, Collier Joel H

机构信息

Department of Surgery, University of Chicago, Chicago, Illinois.

Department of Biomedical Engineering, Duke University, Durham, North Carolina.

出版信息

J Biomed Mater Res A. 2016 Aug;104(8):1853-62. doi: 10.1002/jbm.a.35767. Epub 2016 May 26.

Abstract

Biomaterials used in the context of tissue engineering or wound repair are commonly designed to be "nonimmunogenic." However, previously it has been observed that self-assembled peptide nanofiber materials are noninflammatory despite their immunogenicity, suggesting that they may be appropriate for use in wound-healing contexts. To test this hypothesis, mice were immunized with epitope-containing peptide self-assemblies until they maintained high antibody titers against the material, then gels of the same peptide assemblies were applied within full-thickness dermal wounds. In three different murine dermal-wounding models with different baseline healing rates, even significantly immunogenic peptide assemblies did not delay healing. Conversely, adjuvanted peptide assemblies, while raising similar antibody titers to unadjuvanted assemblies, did delay wound healing. Analysis of the healing wounds indicated that compared to adjuvanted peptide assemblies, the unadjuvanted assemblies exhibited a progression of the dominant T-cell subset from CD4(+) to CD8(+) cells in the wound, and CD4(+) cell populations displayed a more Th2-slanted response. These findings illustrate an example of a significant antibiomaterial adaptive immune response that does not adversely affect wound healing despite ongoing antibody production. This material would thus be considered "immunologically compatible" in this specific context rather than "nonimmunogenic," a designation that is expected to apply to a range of other protein- and peptide-based biomaterials in wound-healing and tissue-engineering applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1853-1862, 2016.

摘要

用于组织工程或伤口修复的生物材料通常设计为“无免疫原性”。然而,此前已观察到自组装肽纳米纤维材料尽管具有免疫原性,但却无炎症反应,这表明它们可能适用于伤口愈合环境。为了验证这一假设,用含表位的肽自组装体对小鼠进行免疫,直至它们对该材料保持高抗体滴度,然后将相同肽组装体的凝胶应用于全层皮肤伤口。在三种具有不同基线愈合率的不同小鼠皮肤创伤模型中,即使是具有显著免疫原性的肽组装体也不会延迟愈合。相反,佐剂化的肽组装体虽然产生与未佐剂化组装体相似的抗体滴度,但确实会延迟伤口愈合。对愈合伤口的分析表明,与佐剂化肽组装体相比,未佐剂化组装体在伤口中显示出优势T细胞亚群从CD4(+)细胞向CD8(+)细胞的转变,并且CD4(+)细胞群体表现出更偏向Th2的反应。这些发现说明了一个显著的抗生物材料适应性免疫反应的例子,尽管持续产生抗体,但该反应不会对伤口愈合产生不利影响。因此,在这种特定情况下,这种材料将被认为是“免疫相容的”,而不是“无免疫原性的”,预计这一名称适用于伤口愈合和组织工程应用中的一系列其他基于蛋白质和肽的生物材料。© 2016威利期刊公司。《生物医学材料研究杂志》A部分:第104A卷:1853 - 1862页,2016年。

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