Watson Emma, Smith Brandon T, Smoak Mollie M, Tatara Alexander M, Shah Sarita R, Pearce Hannah A, Hogan Katie J, Shum Jonathan, Melville James C, Hanna Issa A, Demian Nagi, Wenke Joseph C, Bennett George N, van den Beucken Jeroen J J P, Jansen John A, Wong Mark E, Mikos Antonios G
Department of Bioengineering, Rice University, Houston, TX, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA.
Department of Bioengineering, Rice University, Houston, TX, USA.
Biomaterials. 2020 Oct;256:120185. doi: 10.1016/j.biomaterials.2020.120185. Epub 2020 Jun 23.
Mandibular reconstruction requires functional and aesthetic repair and is further complicated by contamination from oral and skin flora. Antibiotic-releasing porous space maintainers have been developed for the local release of vancomycin and to promote soft tissue attachment. In this study, mandibular defects in six sheep were inoculated with 10 colony forming units of Staphylococcus aureus; three sheep were implanted with unloaded porous space maintainers and three sheep were implanted with vancomycin-loaded space maintainers within the defect site. During the same surgery, 3D-printed in vivo bioreactors containing autograft or xenograft were implanted adjacent to rib periosteum. After 9 weeks, animals were euthanized, and tissues were analyzed. Antibiotic-loaded space maintainers were able to prevent dehiscence of soft tissue overlying the space maintainer, reduce local inflammatory cells, eliminate the persistence of pathogens, and prevent the increase in mandibular size compared to unloaded space maintainers in this sheep model. Animals with an untreated mandibular infection formed bony tissues with greater density and maturity within the distal bioreactors. Additionally, tissues grown in autograft-filled bioreactors had higher compressive moduli and higher maximum screw pull-out forces than xenograft-filled bioreactors. In summary, we demonstrated that antibiotic-releasing space maintainers are an innovative approach to preserve a robust soft tissue pocket while clearing infection, and that local infections can increase local and remote bone growth.
下颌骨重建需要进行功能和美学修复，口腔及皮肤菌群的污染会使其进一步复杂化。已研发出可释放抗生素的多孔间隙保持器，用于局部释放万古霉素并促进软组织附着。在本研究中，给6只绵羊的下颌骨缺损处接种10个金黄色葡萄球菌菌落形成单位；3只绵羊植入未负载的多孔间隙保持器，另外3只绵羊在缺损部位植入负载万古霉素的间隙保持器。在同一手术过程中，将含有自体移植物或异种移植物的3D打印体内生物反应器植入肋骨骨膜附近。9周后，对动物实施安乐死并对组织进行分析。在该绵羊模型中，与未负载的间隙保持器相比，负载抗生素的间隙保持器能够防止覆盖间隙保持器的软组织裂开，减少局部炎症细胞，消除病原体的持续存在，并防止下颌骨尺寸增大。未治疗下颌骨感染的动物在远端生物反应器内形成了密度更高、成熟度更高的骨组织。此外，在填充自体移植物的生物反应器中生长的组织比填充异种移植物的生物反应器具有更高的压缩模量和更高的最大螺钉拔出力。总之，我们证明了释放抗生素的间隙保持器是一种在清除感染的同时保留强大软组织袋的创新方法，并且局部感染可增加局部和远处的骨生长。
