Ink-jet 3D printing as a strategy for developing bespoke non-eluting biofilm resistant medical devices

Chronic infection as a result of bacterial biofilm formation on implanted medical devices is a major global healthcare problem requiring new biocompatible, biofilm-resistant materials. Here we demonstrate how bespoke devices can be manufactured through ink-jet-based 3D printing using bacterial biofilm inhibiting formulations without the need for eluting antibiotics or coatings. Candidate monomers were formulated and their processability and reliability demonstrated. Formulations for in vivo evaluation of the 3D printed structures were selected on the basis of their in vitro bacterial biofilm inhibitory properties and lack of mammalian cell cytotoxicity. In vivo in a mouse implant infection model, Pseudomonas aeruginosa biofilm formation on poly-TCDMDA was reduced by ∼99% when compared with medical grade silicone. Whole mouse bioluminescence imaging and tissue immunohistochemistry revealed the ability of the printed device to modulate host immune responses as well as preventing biofilm formation on the device and infection of the surrounding tissues. Since 3D printing can be used to manufacture devices for both prototyping and clinical use, the versatility of ink-jet based 3D-printing to create personalised functional medical devices is demonstrated by the biofilm resistance of both a finger joint prosthetic and a prostatic stent printed in poly-TCDMDA towards P. aeruginosa and Staphylococcus aureus.

植入式医疗器械表面细菌生物膜形成引发的慢性感染是全球性重大医疗难题，亟需开发兼具生物相容性与抗生物膜性能的新型材料。本研究展示了如何通过喷墨式3D打印技术，使用抗细菌生物膜配方制备定制化医疗器械，无需依赖可洗脱抗生素或表面涂层。我们制备了候选单体配方，并验证了其加工性能与可靠性。本研究基于体外抗细菌生物膜性能与无哺乳动物细胞毒性的标准，筛选出可用于3D打印结构体内评价的配方。在小鼠植入感染模型的体内实验中，与医用级硅胶相比，聚TCDMDA（poly-TCDMDA）表面的铜绿假单胞菌（Pseudomonas aeruginosa）生物膜形成量降低了约99%。通过小鼠整体生物发光成像与组织免疫组化分析，本研究发现打印的医疗器械不仅可抑制器械表面生物膜形成与周围组织感染，还能调节宿主免疫应答。由于3D打印技术可同时用于原型开发与临床器械制造，本研究通过聚TCDMDA打印的手指关节假体与前列腺支架对铜绿假单胞菌（Pseudomonas aeruginosa）及金黄色葡萄球菌（Staphylococcus aureus）均表现出抗生物膜性能，证实了喷墨式3D打印技术在制备个性化功能医疗器械方面的多功能性。