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

Area of Science:

• Biomaterials Science
• Immunology
• Transplantation Biology

Background:

• Biomaterial-based immune modulation aims for localized graft acceptance, avoiding systemic immunosuppression.
• Molecular chirality in biomaterials can influence immune responses.
• Microporous annealed particle (MAP) hydrogels offer a platform for localized immunomodulation.

Purpose of the Study:

• To investigate how molecular chirality within MAP hydrogels governs innate and adaptive immune responses in skin transplantation.
• To determine if chirality modulates alloimmune outcomes and graft acceptance.
• To establish stereochemical control as a design principle for biomaterial-driven tolerance.

Main Methods:

• Engineered injectable MAP hydrogel scaffolds using L- or D-peptides for crosslinking.
• Investigated antigen-presenting cell (APC) activation and trafficking in draining lymph nodes.
• Assessed T cell polarization profiles, graft architecture, and immune responses (DSA, IgG) in syngeneic and allogeneic skin grafts.

Main Results:

• Chirality directed APC activation and trafficking, leading to distinct T cell polarization.
• Mixed-chirality (R-MAP) hydrogels reduced APC co-stimulatory signaling (MHC II, CD80, CD86).
• R-MAP implantation in allogeneic grafts reduced donor-specific antibody formation and IgG responses, attenuating humoral alloimmunity.

Conclusions:

• Molecular chirality in MAP hydrogels is a key factor in modulating immune responses during skin transplantation.
• Mixed-chirality hydrogels promote graft acceptance by reducing alloimmunity.
• Stereochemical control of biomaterials offers a versatile platform for localized immunomodulation in transplantation and regenerative medicine.