2. Academic Validation
  3. Probiotic domestication and engineering enable one-shot treatment for bladder mucosal repair

Probiotic domestication and engineering enable one-shot treatment for bladder mucosal repair

  • Biomaterials. 2025 Jan 25:318:123123. doi: 10.1016/j.biomaterials.2025.123123.
Menglu Li 1,  Shengkai Jin 2,  Yichen Lu 3,  Qingfei Sun 4,  Yuwei Zhang 5,  Peng Jiang 1,  Sha Zhu 1,  Yi Luo 6,  Shan-Chao Zhao 7,  Chao Li 8,  Ninghan Feng 9
Affiliations

Affiliations

  • 1 Department of Urology, Jiangnan University Medical Center, Wuxi, 214000, China; Institute of Urology, Wuxi School of Medicine, Jiangnan University, Wuxi, 214000, China; Department of Urology, Wuxi Medical Center, Nantong University, Nantong, 226007, China.
  • 2 Institute of Urology, Wuxi School of Medicine, Jiangnan University, Wuxi, 214000, China.
  • 3 Department of Urology, Wuxi No. 2 People's Hospital, Nanjing Medical University, Nanjing, 211166, China.
  • 4 School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, China.
  • 5 Department of Urology, Wuxi Medical Center, Nantong University, Nantong, 226007, China.
  • 6 Department of Urology, University of Iowa, Iowa City, IA, 52242, USA. Electronic address: yi-luo@uiowa.edu.
  • 7 Department of Urology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, 510900, China. Electronic address: zhaoshanchao@263.net.
  • 8 School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, China. Electronic address: lchao@hfut.edu.cn.
  • 9 Department of Urology, Jiangnan University Medical Center, Wuxi, 214000, China; Institute of Urology, Wuxi School of Medicine, Jiangnan University, Wuxi, 214000, China; Department of Urology, Wuxi Medical Center, Nantong University, Nantong, 226007, China; Department of Urology, Wuxi No. 2 People's Hospital, Nanjing Medical University, Nanjing, 211166, China. Electronic address: n.feng@njmu.edu.cn.
PMID: 39893782 DOI: 10.1016/j.biomaterials.2025.123123
Abstract

The bladder mucosa is an important blood-urine barrier in the human body, its destruction can lead to distressing cystitis. Traditional treatment approaches often require frequent catheterization and intravesical instillation of hyaluronic acid (HA), which greatly reduces patient compliance and therapeutic efficacy. Herein, we develop a probiotic-based one-shot therapy to repair bladder mucosa with improved convenience, efficacy, and biosafety. To this end, a high-biocompatible probiotic strain is engineered to secrete high-molecular-weight HA controlled by ultrasound stimulation. Meanwhile, a bacterium acclimation-inspired strategy to select Bacterial cells targeting the site of bladder inflammation is also proposed. With just one-shot intravesical administration, these engineered bacteria can strongly adhere to the damaged bladder epithelium, continuously secrete HA, and stimulate the formation of protective living engineered Materials on the bladder. Consequently, varying therapeutic efficacies in damaged murine model, such as reporting the site of inflammation within 28 days, accelerating mucosal repair (such as significantly increased expression of tight junction proteins occludin-1 and ZO-1), modulating innate immune reactions (such as pro-inflammatory factor levels decreased by about 50 %), and even recovering animal motion behaviors, are realized, achieving an improved therapeutic effect without detectable adverse effects.

Keywords

Bladder; Hyaluronic acid; Probiotic therapy; Targeted delivery.

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