Analysis of the Ability of Different Allografts to Act as Carrier Grafts for Local Drug Delivery.

Bone defects and infections pose significant challenges for treatment, requiring a comprehensive approach for prevention and treatment. Thus, this study sought to evaluate the efficacy of various bone allografts in the absorption and release of antibiotics. A specially designed high-absorbency, high-surface-area carrier graft composed of human demineralized cortical fibers and granulated cancellous bone (fibrous graft) was compared to different human bone allograft types. The groups tested here were three fibrous grafts with rehydration rates of 2.7, 4, and 8 mL/g (F(2.7), F(4), and F(8)); demineralized bone matrix (DBM); cortical granules; mineralized cancellous bone; and demineralized cancellous bone. The absorption capacity of the bone grafts was assessed after rehydration, the duration of absorption varied from 5 to 30 min, and the elution kinetics of gentamicin were determined over 21 days. Furthermore, antimicrobial activity was assessed using a zone of inhibition (ZOI) test with S. aureus. The fibrous grafts exhibited the greatest tissue matrix absorption capacity, while the mineralized cancellous bone revealed the lowest matrix-bound absorption capacity. For F(2.7) and F(4), a greater elution of gentamicin was observed from 4 h and continuously over the first 3 days when compared to the other grafts. Release kinetics were only marginally affected by the varied incubation times. The enhanced absorption capacity of the fibrous grafts resulted in a prolonged antibiotic release and activity. Therefore, fibrous grafts can serve as suitable carrier grafts, as they are able to retain fluids such as antibiotics at their intended destinations, are easy to handle, and allow for a prolonged antibiotic release. Application of these fibrous grafts can enable surgeons to provide longer courses of antibiotic administration for septic orthopedic indications, thus minimizing infections.

Optimization of cell-laden bioinks for 3D bioprinting and efficient infection with influenza A virus.

Bioprinting is a new technology, which arranges cells with high spatial resolution, but its potential to create models for viral infection studies has not yet been fully realized. The present study describes the optimization of a bioink composition for extrusion printing. The bioinks were biophysically characterized by rheological and electron micrographic measurements. Hydrogels consisting of alginate, gelatin and Matrigel were used to provide a scaffold for a 3D arrangement of human alveolar A549 cells. A blend containing 20% Matrigel provided the optimal conditions for spatial distribution and viability of the printed cells. Infection of the 3D model with a seasonal influenza A strain resulted in widespread distribution of the virus and a clustered infection pattern that is also observed in the natural lung but not in two-dimensional (2D) cell culture, which demonstrates the advantage of 3D printed constructs over conventional culture conditions. The bioink supported viral replication and proinflammatory interferon release of the infected cells. We consider our strategy to be paradigmatic for the generation of humanized 3D tissue models by bioprinting to study infections and develop new antiviral strategies.