Dynamic immunoengineering: mechanobiology and stimuli-responsive biointerfaces in regeneration and cancer: a comprehensive review

Mechanobiology and stimulus-responsive bio-interfaces have emerged as transformative technologies that allow sophisticated and precise regulation of immune cells for tissue regeneration and cancer therapies, thus driving a paradigm shift in immunoengineering. This review highlights how cell responses to mechanical stimuli contribute to regulating the immune system through integrin signalling, mechanosensitive ion channels, and the YAP/TAZ signalling axis. An overview of smart biomaterials’ designing strategies for sensing mechanical stiffness, temperature, pH, redox status, light, electricity, and enzymatic action is provided, and the roles of smart biomaterials in regeneration of bone, cartilage, skin, nervous tissue, and tumour micro-environment modulation are discussed. Preclinical and clinical evidence suggest that the compounds can drive macrophage polarisation, increase T cell activation, and contribute to the overcome of specific tumour immune escape mechanisms in preclinical ​studies. This also takes on the challenge of bio-material-centered cancer immunotherapy. This involves looking at various types of implantable device, from a new nano-based anti-cancer platform to construct arrays to get greater delivery specificity and minimise side effects, to different combinatorial strategies against cancer. Although there have been promising results, the difficulty issues such as the spatial-temporal heterogeneity of the pathological micro-environment and the processing complexity and regulation problems still challenge the widespread application and implementation. Integration of AI with sophisticated in vitro models suggested for acceleration of translation. The future perspective envisages a closed-loop bio-interface made up of biosensors for dynamic and on-line immunomodulation. These interdisciplinary confluences provide tremendous potential for the field to shift the role of biomaterials from a passive scaffold to an active, programmable immune regulator, thereby developing next-generation personalized regenerative medicine and oncology therapeutics.