The lack of neo-cartilage integration with host tissues is a great challenge for the clinical translation of new technologies for the repair of articular cartilage (AC) defect. Recently, we developed a promising double-layered collagen-based system for targeted delivery of fibroblast growth factor 2 (FGF2) to the subchondral bone for AC repair. The system effectively promoted the regeneration of both cartilage and subchondral bone. However, neo-cartilage integration was unsatisfactory, which might be due to the presence of a zone of cell death (ZCD) in the cartilage induced by injury. Here, we hypothesized that maintaining cell viability in the region surrounding the defect and decreasing the size of ZCD by using chondroprotective agents such as insulin-like growth factor-1 (IGF-1), might be an effective strategy to improve neo-cartilage integration. A targeted delivery system for IGF-1 to cartilage based on the FGF2 delivery system was formulated to weaken the impact on the effects of FGF2. The two growth factors were incorporated into the different layers of the membrane without interdiffusion. Due to the different densities of collagen fibers in the different layers, the in vitro and in vivo assays demonstrated that both proteins were released via unidirectional diffusion without mixing or lateral diffusion. Particularly, the released IGF-1 increased the viability of chondrocytes, decreased the ZCD size, and enhanced the integration of regenerative neo-cartilage with host tissues, without any undesirable effects on the FGF2mediated regeneration of cartilage and subchondral bone. Taken together, our findings demonstrate that the collagen fiber membrane-aided chondroprotective-based strategy is an effective way to improve neo-cartilage integration.