Engineering Antigen-Specific Tolerance to an Artificial Protein Hydrogel

Artificial protein hydrogels are an emerging class of
biomaterials
with numerous prospective applications in tissue engineering and regenerative
medicine. These materials are likely to be immunogenic due to their
frequent incorporation of novel amino acid sequence domains, which
often serve a functional role within the material itself. We engineered
injectable “self” and “nonself” artificial
protein hydrogels, which were predicted to have divergent immune outcomes in vivo on the basis of their primary amino acid sequence.
Following implantation in mouse, the nonself gels raised significantly
higher antigel antibody titers than the corresponding self gels. Prophylactic
administration of a fusion antibody targeting the nonself hydrogel
epitopes to DEC-205, an endocytic receptor involved in Treg induction, fully suppressed the elevated antibody titer against
the nonself gels. These results suggest that the clinical immune response
to artificial protein biomaterials, including those that contain highly
antigenic sequence domains, can be tuned through the induction of
antigen-specific tolerance.