Biomedical device-associated infection is one of the most common and problematic complications faced by millions of patients worldwide. The current antibiotic therapy strategies face challenges, the most serious of which is antibiotic resistance. Studies have shown that the systemic level of interleukin 12 (IL-12) decreases following major injuries resulting in decreased cell-mediated immune response. Here we report the development of IL-12 nanoscale coatings using electrostatic layer-by-layer self-assembly nanotechnology. We found that IL-12 nanoscale coatings at the implant/tissue interface substantially decrease infections in vivo, and IL-12 nanoscale coatings are advantageous over traditional treatments. This approach could be a revolutionary step toward preventing device-associated infections using a non-antibiotic approach.

Allogeneic SDSC-based premature tissue constructs are a promising stem cell-based approach for cartilage defects. Although in vitro data suggest that contaminated macrophages affected the quality of SDSC-based premature cartilage, effects of macrophages on in vivo tissue regeneration and integration necessitate further investigation.

The increasing clinical incidence and host risk of open fracture-associated infections, as well as the reduced effectiveness of conventional antibiotics to treat such infections, have driven the development of new therapies for the prophylaxis of open fracture-associated infections. We investigated percutaneous supplementation of a natural cytokine (i.e. interleukin 12p70 or IL-12) at an open fracture site to reduce open fracture-associated infections. We also determined the efficacy of the combination therapy of IL-12 and conventional antibiotic therapy in the prophylaxis of open fracture-associated infections. An open femur fracture infection model was produced by direct inoculation of a clinical isolate of Staphylococcus aureus after creating a femur fracture using rats. The animals were assigned to one of four groups: no drug administration, percutaneous supplementation of IL-12, intraperitoneal administration of the antibiotic ampicillin, or percutaneous IL-12 in combination with intraperitoneal ampicillin. Animals were euthanized at post-operative days 6, 10, 14, and 21. Percutaneous IL-12 led to a reduction in infection at post-operative days 6 and 10. For the first time, exogenous IL-12 was found to have additive effects in the prevention of infection when combined with conventional treatment (i.e. antibiotic therapy). Combination therapy of ampicillin and IL-12 substantially reduced the infection rate at post-operative day 6 and also decreased the time needed for complete inhibition of infection. Therefore, exogenous IL-12, providing a mechanism of protection independent of antibiotic resistance, complements the routine use of antibiotics.

The use of xenogeneic tissues offers many advantages with respect to availability, quality control, and timing of tissue harvest. Our previous study indicated that implantation of premature tissue constructs from allogeneic synovium‐derived stem cells (SDSCs) facilitated cartilage tissue regeneration. The present study investigated the feasibility of xenoimplantation of SDSC‐based premature tissue constructs for the repair of osteochondral defects. Porcine SDSCs were mixed with fibrin gel, seeded in polyglycolic acid (PGA) scaffolds, and cultured in a rotating bioreactor system supplemented for 1 month with growth factor cocktails. The engineered porcine premature tissues were implanted to repair surgically induced osteochondral defects in the medial femoral condyles of 12 rabbits. Three weeks after surgery, the xenoimplantation group exhibited a smooth, whitish surface while the untreated control remained empty. Surprisingly, 6 months after surgery, the xenoimplantation group displayed some tissue loss while the untreated control group was overgrown with fibrocartilage tissue. In the xenoimplantation group, chronic inflammation was observed in synovial tissue where porcine major histocompatibility complex (MHC) class II antigen positively stained in the engulfed foreign bodies. In addition, porcine source cells also migrated from the implantation site and may have been responsible for the observed loss of glycosaminoglycans (GAGs) underneath surrounding articular cartilage. The histological score was much worse in the xenoimplanted group than in the untreated control. Our study suggested that SDSC‐based xenogeneic tissue constructs might cause delayed immune rejection. Xenotransplantation may not be an appropriate approach to repair osteochondral defects. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1064–1070, 2010

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