The adaptive immune response to porous regenerated keratin as a bone graft substitute in an ovine model

Abstract

Reconstituted keratin is a novel bone graft material when prepared as a rigid scaffold. Understanding the immunogenicity of this material is important to determine whether this substance is a viable surgical option. Previous studies have shown no innate immune system activation in response to reconstituted keratin implants. To examine antibody-mediated immune responses to reconstituted keratin implants, bone and blood samples were taken from twelve sheep with surgically created tibial defects containing such implants. RT-PCR was used to detect mRNA of the inflammatory marker SOCS 3 in local bony tissue, and a novel immunohistochemistry assay developed to detect antikeratin antibodies in serum. Two animals were sacrificed per time-point at weeks 1, 2, 4, 6, 8 and 12. Time points for serum analysis included baseline (pre-surgery) and all other time points; mRNA analysis examined samples from all time points. No upregulation in antikeratin antibodies or SOCS 3 mRNA was observed at any time point, indicating that reconstituted keratin implants do not trigger an adaptive immune response in vivo in an ovine model. These findings provide the platform for further development of keratin implants in other mammalian models to define its immunogenic profile and safety.