Implanted devices such as joint replacements, pacemakers, and heart valves can become infected when bacterial pathogens colonize their surfaces, often leading to revision surgeries, prolonged antibiotic treatments, or severe complications. In orthopedic procedures, thousands of patients each year face device-related infections despite preventive measures. These challenges highlight the need for improved strategies that reduce bacterial risk and strengthen immune protection. Now, a next-generation biomaterial vaccine can train the immune system to protect orthopedic implants from infection.

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University (Boston, MA, USA) and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS, Cambridge, MA, USA) have developed a slowly biodegradable scaffold vaccine to attract immune cells and present a broad set of antigens. These scaffolds incorporate molecules that recruit dendritic cells and present many Staphylococcus aureus-derived pathogen-associated molecular patterns captured using engineered FcMBL technology.

The biomaterial acts as a structured training site where dendritic cells sample antigens before migrating to lymph nodes to coordinate targeted immune responses. By releasing immune-activating cues gradually, the platform avoids rapid dispersal typical of soluble vaccines. This method engages T cell populations alongside antibody responses, offering a more sustained and coordinated defense. Preclinical development also explored the role of PAMP signatures in fine-tuning vaccine potency.

The study, published in PNAS, compared the biomaterial vaccines with conventional soluble formulations in mice. When challenged with pathogenic S. aureus, vaccinated animals showed a dramatically reduced bacterial burden on implanted devices. Tests showed roughly a 100-fold improvement in bacterial suppression compared with control vaccines containing the same components. Importantly, material made with antigens from methicillin-sensitive strains also protected against methicillin-resistant strains.

The team further demonstrated that single antigens identified from PAMP profiling could provide partial protection, indicating the possibility of streamlined formulations. Device-infection models confirmed that prior vaccination significantly lowered bacterial accumulation. The gradual activation of immune pathways and coordinated T helper cell responses appeared central to the observed benefit. Blood and tissue analyses suggested durable engagement of immune networks needed for device protection.

These findings indicate that biomaterial vaccines may offer a new path for preventing infections in orthopedic implants, expanding possibilities beyond traditional soluble vaccines. By incorporating complex antigen repertoires and providing sustained immune activation, the platform may overcome limitations that hindered earlier vaccine attempts against S. aureus. Broader applications could include safeguarding long-term indwelling devices across cardiology, neurosurgery, or vascular medicine.

Future efforts aim to identify which PAMP signatures generate the strongest immunity and to improve antigen selection. Personalized vaccines may eventually be produced using PAMPs isolated from a patient’s own bacterial strains before surgery. Researchers also plan to refine biomaterial formulations, explore simplified antigen sets, and assess how this strategy could integrate with device-surgery workflows. Continued animal studies and translational research will define pathways toward clinical adoption.

“One could envision a future in which clinical researchers rapidly identify relevant PAMPs in patient-specific S. aureus strains obtained through simple non-invasive procedures ahead of surgeries to produce effective personalized biomaterial vaccines that protect implanted orthopedic devices from infections,” said Alexander Tatara, M.D., Ph.D., first author of the study.

“But beyond orthopedic implants, it could also become a versatile and easy-to-apply safeguard for many other kinds of devices dwelling for prolonged times in the human body that can create similar problems,” added Wyss Founding Director Donald Ingber, M.D.

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