Targeted immune modulation through smart biomaterials and programmable biopharmaceuticals: A review

Immune-mediated diseases remain a major global health challenge, while current immunotherapies are often limited by systemic toxicity, poor tissue selectivity, and insufficient control over immune responses. This review examines recent advances in targeted immune modulation through smart biomaterials, programmable biopharmaceuticals, and hybrid biomaterial-biologic systems. A structured literature review was conducted using peer-reviewed studies published between 2022 and 2026 from major biomedical databases. The reviewed evidence indicates that smart biomaterials can respond to disease-associated microenvironmental signals, such as pH changes, hypoxia, oxidative stress, and inflammatory enzymes, enabling localized and context-dependent therapeutic activity. Programmable biopharmaceuticals further enhance precision by directing immune-cell behavior and molecular signaling through engineered biological mechanisms. In addition, hybrid biomaterial-biologic platforms combine environmental responsiveness with the potency of biologic therapeutics, improving immune targeting and reducing unintended systemic effects. Collectively, these technologies support a transition from conventional systemic immunomodulation toward adaptive and site-specific immune control. Despite significant progress, important challenges remain, including biological complexity, manufacturing scalability, long-term safety assessment, and regulatory translation. Nevertheless, the convergence of biomaterials science, synthetic biology, and immunoengineering is creating new opportunities for precision immunotherapy. Targeted immune modulation through programmable and responsive therapeutic systems represents a promising framework for developing safer, more effective, and clinically durable next-generation immunomodulatory therapies.