Y. Vigneswaran1, H. Han1, J. Handley1, T. Sun1, J. Collier1 1University Of Chicago,Department Of Surgery,Chicago, IL, USA
Introduction: Peptide nanofibers have received significant interest as scaffolds for tissue repair, wound healing, and regeneration. These self-assembling peptide systems have been exploited for their modularity, ease of synthesis, ability to incorporate multiple signaling components, and structural similarity to native extracellular matrix. Recently, we have observed that these materials can be formulated to raise strong immune responses by incorporating specific T cell and B cell epitopes, yet they elicit no detectable inflammation at sites of delivery. We sought to determine whether this nanofiber immunogenicity precluded the use of the materials in wound healing contexts, hypothesizing that some antibody responses may be consistent with the performance of the materials in tissue defects.
Methods: In mice, an excisional dermal wound healing model was used to study the effects of active immune responses at the site of healing. Our worked used the self-assembling peptide Q11 (QQKFQFQFEQQ) and the OT-II antigen from the protein ovalbumin (containing a T cell and B cell epitope). Mice were either immunized with dilute solutions of the epitope-bearing nanofibers or not immunized. After vigorous anti-peptide immune responses were established, full thickness dermal wounds were created. Immunized mice received the epitope-bearing nanofiber scaffold in the wound (n=6), whereas non-immunized mice received either the nanofiber scaffold (n=6) or phosphate-buffered saline (n=6) in their wounds. Mice were sacrificed at 7 days and 16 days post wounding. Wounds were harvested, fixed, paraffin embedded, and examined histologically.
Results: Immunized mice raised high antibody titers against the peptide scaffold. However, their wound healing did not differ significantly differ from control groups with respect to epithelial gap or granulation tissue formation at day 7 (p=0.95, p=0.25) or day 16 (p=0.72, p=0.62), even when additional immunostimulating peptide nanofibers were placed in the wound. Additionally, immunohistochemistry confirmed the presence of leukocytes at the site of the wound and an active immune response.
Conclusion: We conclude that the phenotype of the immune response raised by peptide nanofibers is compatible with using such materials within healing defects. This finding is consistent with previous studies from our group showing that even vigorous antibody responses raised by the materials are not associated with any measurable inflammation at their sites of delivery, but it runs counter to the generally held view to avoid anti-biomaterial immune responses in tissue engineering applications. Further basic investigation may help clarify whether the non-inflammatory character of these materials exerts itself via a passive or active mechanism.