TY - JOUR
T1 - 3D Bioprinted Scaffolds Containing Viable Macrophages and Antibiotics Promote Clearance of Staphylococcus aureus Craniotomy-Associated Biofilm Infection
AU - Aldrich, Amy
AU - Kuss, Mitchell A.
AU - Duan, Bin
AU - Kielian, Tammy
N1 - Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2019/4/3
Y1 - 2019/4/3
N2 - Craniotomy involves the removal of a skull fragment to access the brain, such as during tumor or epilepsy surgery, which is immediately replaced intraoperatively. The infection incidence after craniotomy ranges from 0.8 to 3%, with approximately half caused by Staphylococcus aureus (S. aureus). To mitigate infectious complications following craniotomy, we engineered a three-dimensional (3D) bioprinted bone scaffold to harness the potent antibacterial activity of macrophages (Mφs) together with antibiotics using a mouse S. aureus craniotomy-associated biofilm model that establishes a persistent infection on the bone flap, subcutaneous galea, and brain. The 3D scaffold contained rifampin and daptomycin printed in a composite slurry, with viable Mφs incorporated into a hydrogel-based bioink, which was assessed for both the treatment and prevention of craniotomy-associated infections in the mouse model. For the treatment paradigm, the bone flap was removed at day 7 post infection after a mature biofilm had formed and was replaced with a 3D printed antibiotic scaffold, with or without Mφ incorporation. Bacterial burdens in the galea and brain were reduced by at least 100-fold at early time points, which was potentiated by bioprinting viable Mφs into the 3D antibiotic scaffold. We also examined a prevention paradigm, where the scaffolds were placed at the time of surgery and challenged with S. aureus one day later at the surgical site. Interestingly, unlike the treatment paradigm, the incorporation of viable Mφs into the 3D antibiotic scaffold did not enhance bacterial clearance compared to that of antibiotic alone. With further refinement, our 3D bioprinted scaffold represents a potential treatment modality, as it delivers therapeutic antibiotic levels more rapidly than systemic administration, based on its proximity to the infection site. In addition, the incorporation of viable Mφs into the 3D scaffold is an important advance, which demonstrated an improved therapeutic benefit for the treatment of established biofilms that represent the most clinically challenging scenario.
AB - Craniotomy involves the removal of a skull fragment to access the brain, such as during tumor or epilepsy surgery, which is immediately replaced intraoperatively. The infection incidence after craniotomy ranges from 0.8 to 3%, with approximately half caused by Staphylococcus aureus (S. aureus). To mitigate infectious complications following craniotomy, we engineered a three-dimensional (3D) bioprinted bone scaffold to harness the potent antibacterial activity of macrophages (Mφs) together with antibiotics using a mouse S. aureus craniotomy-associated biofilm model that establishes a persistent infection on the bone flap, subcutaneous galea, and brain. The 3D scaffold contained rifampin and daptomycin printed in a composite slurry, with viable Mφs incorporated into a hydrogel-based bioink, which was assessed for both the treatment and prevention of craniotomy-associated infections in the mouse model. For the treatment paradigm, the bone flap was removed at day 7 post infection after a mature biofilm had formed and was replaced with a 3D printed antibiotic scaffold, with or without Mφ incorporation. Bacterial burdens in the galea and brain were reduced by at least 100-fold at early time points, which was potentiated by bioprinting viable Mφs into the 3D antibiotic scaffold. We also examined a prevention paradigm, where the scaffolds were placed at the time of surgery and challenged with S. aureus one day later at the surgical site. Interestingly, unlike the treatment paradigm, the incorporation of viable Mφs into the 3D antibiotic scaffold did not enhance bacterial clearance compared to that of antibiotic alone. With further refinement, our 3D bioprinted scaffold represents a potential treatment modality, as it delivers therapeutic antibiotic levels more rapidly than systemic administration, based on its proximity to the infection site. In addition, the incorporation of viable Mφs into the 3D scaffold is an important advance, which demonstrated an improved therapeutic benefit for the treatment of established biofilms that represent the most clinically challenging scenario.
KW - 3D bioprinting
KW - Staphylococcus aureus
KW - biofilm infection
KW - craniotomy
KW - macrophage
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U2 - 10.1021/acsami.9b00264
DO - 10.1021/acsami.9b00264
M3 - Article
C2 - 30855125
AN - SCOPUS:85063780288
SN - 1944-8244
VL - 11
SP - 12298
EP - 12307
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
IS - 13
ER -