Microporous annealed particle scaffold integrated with autologous tumor cells for personalized postsurgical tumor therapy.

Abstract

Biomaterial scaffolds hold great potential for addressing tumor recurrence and tissue defects following surgical tumor resection; however, personalized therapy remains a critical barrier to their clinical translation. To address this issue, we developed an autologous tumor cell-integrated microporous annealed particle (MAP) scaffold co-delivering an immune adjuvant and an indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor for tumor postoperative therapy. This scaffold was fabricated using microfluidic electrospray combined with step-by-step crosslinking technology. The injectable microspheres, prior to annealing, can be directly delivered into the defect site and conform to its shape upon crosslinking, forming a stabilized, porous structure. Featuring interconnected pores that facilitate cell infiltration and proliferation, the scaffold demonstrated effective tissue repair in mice subjected to full-thickness skin excision. Within the scaffold, cryo-inactivated tumor cells and the immune adjuvant recruit and activate dendritic cells (DCs) in situ, stimulating a robust antitumor immune response. This response is further amplified by the IDO1 inhibitor, which reverses immunosuppression by inhibiting regulatory T cells (Tregs). Consequently, the scaffold exhibited remarkable anti-recurrence efficacy and prolonged survival in a melanoma mouse model. These properties highlight the significant potential of our personalized microporous hydrogel particle scaffold for efficient postoperative antitumor therapy and tissue regeneration. STATEMENT OF SIGNIFICANCE: Tumor recurrence and tissue defects represent significant challenges following surgical tumor removal in cancer patients. Meanwhile, a critical barrier to the clinical translation of postoperative biomaterial scaffolds is the lack of personalization for both antitumor therapy and tissue reconstruction. Here, we developed a personalized microporous annealed particle (MAP) scaffold that integrates autologous tumor cells, immune adjuvant, and IDO1 inhibitor to simultaneously address tumor recurrence and tissue defects. Personalized antitumor therapy is achieved by the injectable MAP scaffold through a tumor vaccine formed from autologous tumor-derived cells within the scaffold, eliciting tumor-specific T-cell responses that are further amplified by reversing the local immunosuppressive microenvironment. Personalized tissue repair is also enabled by such scaffold, which conforms to irregular wound shapes and supports cell infiltration. This work establishes a paradigm that unifies personalized immunotherapy with personalized tissue repair, offering substantial promise for postsurgical cancer therapy.