Peptide biomaterials raising adaptive immune responses in wound healing contexts

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. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1853-1862, 2016.