Bone defect repair in elderly patients is often hindered by limited osteogenic potential, delayed healing, and a high incidence of postoperative complications. Conventional approaches relying on exogenous growth factors face challenges such as high costs, limited biocompatibility, and potential oncogenic risks. Chronic inflammation-induced inflammaging is a key factor contributing to impaired bone healing and non-union in aged individuals. Considering the biomechanically dynamic environment at the interface of soft tissue (skin) and hard tissue (bone), we propose a mechanotransduction-driven immunointegration strategy to mitigate inflammaging. We hypothesize that mechanical interactions between implant materials and surrounding tissues can either exacerbate or alleviate chronic inflammation, thereby influencing bone repair outcomes. In vitro studies revealed that a substrate stiffness of approximately 80 kPa effectively suppressed inflammaging in senescent macrophages by modulating the IL-17/TNF signaling axis. As a proof of concept, cranial defect models in aged mice demonstrated that an 80 kPa stiffness substrate attenuated inflammation in both skin and bone tissues by inhibiting the mechanoreceptor Piezo1. This mechanoregulation enhanced osteogenesis and facilitated tissue integration, promoting more efficient bone regeneration in elderly subjects. This immuno-integrative strategy introduces a novel materials design paradigm, emphasizing the importance of biomechanical cues at tissue interfaces, and paves the way for next-generation implant materials tailored for optimal immunomodulation and tissue repair.