A Precisely Controlled Long-Acting Immunosuppression Platform Enables Prolonged Survival of Vascularized Composite Allografts

PRECISE, an in situ-forming depot for rat hindlimb transplants, maintained systemic tacrolimus and rapamycin within the therapeutic window for over 300 days.

• Why it matters: Lifelong immunosuppression in vascularized composite allotransplantation is constrained by adherence limits and tacrolimus peak–trough swings, while depot approaches can cause early burst or prolonged supratherapeutic exposure.
• What they did: The platform combines a polymeric matrix with selected small-molecule excipients that interact with tacrolimus to modulate solvent dynamics during phase inversion, and it can enable controlled tacrolimus–rapamycin co-delivery. In rats, monthly intragraft dosing was tested, and in fully MHC-mismatched SLA Class I and II pigs it was validated through 90 days.
• The result: In rats, monthly dosing prolonged graft survival, expanded regulatory T cells, and induced donor-specific hyporesponsiveness; in SLA Class I/II pigs it preserved graft vascular integrity and achieved graft survival through 90 days.

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