AI‐Optimized 3D‐Printed Dual‐Layer Implant: Resolving Chemo‐Immunotherapy Sequential Administration Dilemma for Colorectal Cancer Peritoneal Metastasis

Abstract

ABSTRACT The synergistic integration of chemotherapy and immunotherapy represents the most promising strategy for enhancing therapeutic efficacy in cancer treatment. Chemotherapy initiates the therapeutic cascade by inducing immunogenic cell death (ICD), thereby releasing tumor antigens and prime immune sensitization. Subsequently, immunotherapy blocks immune evasion pathways, resulting in a coordinated relay‐like antitumor response. This temporally coordinated sequence maximizes synergistic therapeutic efficacy. However, current clinical practice cannot support the sequential and sustained administration of chemotherapy and immunotherapy. This study innovatively integrates artificial intelligence (AI) with 3D printing technology to develop a dual‐layer drug‐loaded implant (LEH@OG) to achieve precise spatiotemporally controlled sequential drug release. The AI model precisely predicted exposure time of the inner gel layer in advance by optimizing parameters such as outer shell thickness and concentration, thereby realizing an on‐demand sequential release process. This study demonstrates that combining AI with 3D printing enables precise sequential delivery of chemotherapy‐immunotherapy agents, providing a core solution for establishing personalized colorectal cancer peritoneal metastasis (CCPM) therapeutic platforms, while also offering a new paradigm for synergistic treatment of other solid tumors.