Development of a humanized mouse model that recapitulates the fibrotic response to biomaterial implants

Implanted biomedical devices reside within tens of millions of patients in the United States alone, and are involved in millions of new surgeries every year. They comprise a major component of modern medicine and are essential for many clinical applications ranging from hip/knee replacement, tissue repair/reconstruction, controlled release, sensing, and cell transplantation. Limiting therapeutic performance and lifespan, immune-mediated foreign body rejection results in sequestration behind dense layers of fibrotic scar tissue. Current approaches for management of long-term biomedical device implantation often involve broad-spectrum anti-inflammatories. However, these agents are not specific to individual immune populations, and have side effects in vivo . To avoid such issues, improved biomaterials need to be identified with reduced immunogenicity. Deeper understanding of immune-mediated foreign body responses was leveraged to generate a variant of the humanized mouse model, previously unreported in the field of host rejection of biomaterial implants, that is capable of recapitulating fibrosis. Here, we present this model in comparison to wildtype systems, including rodents and non-human primates. Cellular and cytokine responses were determined with numerous biomaterials—hydrogel alginate, ceramic glass, and polymer polystyrene, across multiple implant sites. This model allows us to investigate human immune cells interacting directly with implantables, without putting patients at risk. It is our hope this model can be used as a pre-clinical diagnostic tool for screening implantable synthetic as well as natural materials for immunogenicity.