Chirality-Encoded Biomaterials Regulate Local and Systemic Immune Responses in Transplantation

Area of Science:

• Biomaterials Science
• Immunology
• Transplantation Biology

Background:

• Biomaterial-based immune modulation can achieve localized graft acceptance without systemic immunosuppression.
• Molecular chirality is a key material property that can influence biological interactions.

Purpose of the Study:

• To investigate how molecular chirality within microporous annealed particle (MAP) hydrogels influences innate and adaptive immune responses in skin transplantation.
• To determine if chirality can modulate alloimmune outcomes and promote graft acceptance.

Main Methods:

• Engineered injectable MAP hydrogel scaffolds using microgels crosslinked with L- or D-peptides.
• Assessed antigen-presenting cell (APC) activation and trafficking in draining lymph nodes.
• Evaluated T cell polarization profiles, graft architecture, and immune responses in syngeneic and allogeneic skin transplants.

Main Results:

• Chirality directed APC activation and trafficking, leading to distinct T cell polarization.
• Mixed-chirality MAP (R-MAP) reduced APC co-stimulatory signaling and preserved graft integration in syngeneic transplants.
• In allogeneic grafts, R-MAP reduced donor-specific antibody formation and humoral alloimmunity.

Conclusions:

• Stereochemical control of biomaterial composition is a viable design principle for modulating immune responses.
• Mixed-chirality MAP hydrogels offer a platform for localized, chirality-guided immunomodulation.
• These findings have implications for transplantation, regenerative medicine, and biomaterial-driven tolerance strategies.