Fotouh Bassam, Kyser Anthony J, Mahmoud Mohamed Y, Frieboes Hermann B
Department of Bioengineering, University of Louisville, Louisville, KY, USA.
Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Egypt.
Biomed Eng Adv. 2025 Jun;9. doi: 10.1016/j.bea.2025.100163. Epub 2025 Apr 2.
A novel strategy delivering both metronidazole and via 3D-printed scaffolds was recently shown to target pathogens in bacterial vaginosis (BV) while promoting beneficial microflora with sustained probiotic release, with the objective to facilitate user treatment adherence. This study developed an integrated experimental/computational platform to evaluate dual therapeutic strategy efficacy over a wide range of system dynamics, towards the goal of personalized therapy design. Experiments evaluated and interactions under controlled glucose concentrations , including bacterial growth, glucose consumption, lactic acid production, and pH. These data informed parameters of a novel computational model simulating the vagina, incorporating nutrient dynamics, bacterial interactions, and dual release of antibiotics and probiotics from 3D-printed scaffolds. Efficacy of varying concentrations of antibiotics and probiotics was assessed via sensitivity analyses. Experimental results demonstrate that outcompetes at lower glucose concentrations, while dominates at higher glucose levels. The computational model replicated these dynamics and projected that dual therapy could significantly suppress while promoting , even at lower drug dosages and probiotic CFU counts. Results were validated against data from 3D-printed dual release scaffolds. Simulated dual treatment enhanced lactic acid production and decreased vaginal pH, creating an unfavorable environment for pathogenic bacteria and shifting the microbiome composition towards the beneficial microflora. We conclude that an integrated experimental/computational modeling approach enables detailed evaluation of pathogenic and host bacteria interactions in the vaginal microbiome. This approach could advance personalized treatment for BV that eradicates pathogens while simultaneously restoring beneficial microflora.
最近有研究表明，一种通过3D打印支架同时递送甲硝唑和益生菌的新策略能够靶向治疗细菌性阴道病（BV）的病原体，同时通过持续释放益生菌来促进有益微生物群的生长，目的是提高用户的治疗依从性。本研究开发了一个综合实验/计算平台，以评估在广泛的系统动力学范围内双重治疗策略的疗效，目标是设计个性化治疗方案。实验评估了在受控葡萄糖浓度下益生菌和病原体的相互作用，包括细菌生长、葡萄糖消耗、乳酸产生和pH值。这些数据为一个模拟阴道的新型计算模型提供了参数，该模型纳入了营养动力学、细菌相互作用以及3D打印支架中抗生素和益生菌的双重释放。通过敏感性分析评估了不同浓度抗生素和益生菌的疗效。实验结果表明，在较低葡萄糖浓度下益生菌胜过病原体，而在较高葡萄糖水平下病原体占主导。计算模型重现了这些动力学，并预测即使在较低药物剂量和益生菌CFU数量下，双重疗法也能显著抑制病原体，同时促进益生菌生长。结果通过3D打印双释放支架的数据得到验证。模拟的双重治疗增强了乳酸产生并降低了阴道pH值，为病原菌创造了不利环境，并使微生物群组成向有益微生物群转变。我们得出结论，综合实验/计算建模方法能够详细评估阴道微生物群中病原菌与宿主细菌的相互作用。这种方法可以推动BV的个性化治疗，既能根除病原体，又能同时恢复有益微生物群。
