Enantiomer-Dependent Supramolecular Immunosuppressive Modulation for Tissue Reconstruction

Abstract

Modulating the properties of biomaterials in terms of the host immune response is critical for tissue repair and regeneration. However, it is unclear how the preference for the cellular microenvironment manipulates the chiral immune responses under physiological or pathological conditions. Here, we reported that in vivo and in vitro oligopeptide immunosuppressive modulation was achieved by manipulation of macrophage polarization using chiral tetrapeptide (Ac-FFFK-OH, marked as FFFK) supramolecular polymers. The results suggested that chiral FFFK nanofibers can serve as a defense mechanism in the restoration of tissue homeostasis by upregulating macrophage M2 polarization via the Src-STAT6 axis. More importantly, transiently acting STAT6, insufficient to induce a sustained polarization program, then passes the baton to EGR2, thereby continuously maintaining the M2 polarization program. It is worth noting that the L-chirality exhibits a more potent effect in inducing macrophage M2 polarization than does the D-chirality, leading to enhanced tissue reconstruction. These findings elucidate the crucial molecular signals that mediate chirality-dependent supramolecular immunosuppression in damaged tissues while also providing an effective chiral supramolecular strategy for regulating macrophage M2 polarization and promoting tissue injury repair based on the self-assembling chiral peptide design.

The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples

“…As a result, pharmaceutical preparations, such as Thymogen and Thymodepressin, as well as stimulants and suppressors of the immune response, were introduced into clinical practice [77]. A new generation of the Glu-Trp peptide family derivatives as orally active peptidomimetics expresses the same type of activities as the first generation [107][108][109][110].…”

Chiral MoS2@BC fibrous membranes selectively promote peripheral nerve regeneration

“…Furthermore, Mu et al showed that the chiral tetrapeptide nanofibers can serve as a defense mechanism in the restoration of tissue homeostasis by upregulating macrophage M2 polarization via the Src-STAT6 axis. And the L-chirality exhibited a more potent effect in inducing macrophage M2 polarization than does the D-chirality, leading to enhanced tissue reconstruction [ 68 ], indicating that chiral materials can promote tissue repair through immunomodulation. Sun et al showed that macrophages exhibited distinct differences in the adhesion and activation behaviors on the different enantiomers’ modified surfaces [ 69 ].…”