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.
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.
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DOI：
10.1002/jbm.a.35767
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发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
Collier JH
中科院分区：
文献类型：
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作者：
Vigneswaran Y;Han H;De Loera R;Wen Y;Zhang X;Sun T;Mora-Solano C;Collier JH
用于组织工程或伤口修复的生物材料通常被设计为“非免疫原性”。然而，先前已经观察到，自组装肽纳米纤维材料尽管具有免疫原性，但具有非炎症性，这表明它们可能适合用于伤口愈合。为了验证这一假设，用含有表位的肽自组装体免疫小鼠，直到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。在三种基线愈合率不同的小鼠皮肤损伤模型中，即使是显著的免疫原性肽组装也不会延迟愈合。相反，佐剂肽组合，虽然提高类似的抗体滴度与非佐剂组合，确实延迟伤口愈合。对愈合伤口的分析表明，与佐剂肽组合相比，非佐剂肽组合在伤口中表现出显性T细胞亚群从CD4+向CD8+细胞的进展，CD4+细胞群体表现出更多的th2倾斜反应。这些发现说明了一个重要的抗生物材料适应性免疫反应的例子，尽管正在产生抗体，但它不会对伤口愈合产生不利影响。因此，在这种特殊情况下，这种材料将被认为是“免疫相容的”，而不是“非免疫原性的”，这一称号预计将适用于一系列其他基于蛋白质和肽的生物材料，用于伤口愈合和组织工程应用。
Biomaterials used in the context of tissue engineering or wound repair are commonly designed to be “non-immunogenic”. However, previously it has been observed that self-assembled peptide nanofiber materials are non-inflammatory 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 anti-biomaterial 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 “non-immunogenic”, a designation that is expected to apply to a range of other protein and peptide-based biomaterials in wound healing and tissue engineering applications.