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Bladder Regeneration Using a Polycaprolactone Scaffold with a Gradient Structure and Growth Factors in a Partially Cystectomized Rat Model

Journal of Korean Medical Science 2020년 35권 41호 p.374 ~ 374
김호용, 전소영, 이은혜, 김보미, 하윤석, 정재욱, 이준녕, 김범수, 오세행, 권태균,
소속 상세정보
김호용 ( Kim Ho-Yong ) - Dankook University Department of Nanobiomedical Science
전소영 ( Chun So-Young ) - Kyungpook National University Hospital Biomedical Research Institute
이은혜 ( Lee Eun-Hye ) - Kyungpook National University Hospital Joint Institution for Regenerative Medicine
김보미 ( Kim Bo-Mi ) - Kyungpook National University Hospital Biomedical Research Institute
하윤석 ( Ha Yun-Sok ) - Kyungpook National University Hospital Department of Urology
정재욱 ( Chung Jae-Wook ) - Kyungpook National University School of Medicine Department of Urology
이준녕 ( Lee Jun-Nyung ) - Kyungpook National University School of Medicine Department of Urology
김범수 ( Kim Bum-Soo ) - Kyungpook National University Hospital Department of Urology
오세행 ( Oh Se-Heang ) - Dankook University Department of Nanobiomedical Science
권태균 ( Kwon Tae-Gyun ) - Kyungpook National University School of Medicine Department of Urology

Abstract


Background: Tissue engineering can be used for bladder augmentation. However, conventional scaffolds result in fibrosis and graft shrinkage. This study applied an alternative polycaprolactone (PCL)-based scaffold (diameter = 5 mm) with a noble gradient structure and growth factors (GFs) (epidermal growth factor, vascular endothelial growth factor, and basic fibroblast growth factor) to enhance bladder tissue regeneration in a rat model.

Methods: Partially excised urinary bladders of 5-week-old male Slc:SD rats were reconstructed with the scaffold (scaffold group) or the scaffold combined with GFs (GF group) and compared with sham-operated (control group) and untreated rats (partial cystectomy group). Evaluations of bladder volume, histology, immunohistochemistry (IHC), and molecular markers were performed at 4, 8, and 12 weeks after operation.

Results: The bladder volumes of the scaffold and GF group recovered to the normal range, and those of the GF group showed more enhanced augmentation. Histological evaluations revealed that the GF group showed more organized urothelial lining, dense extracellular matrix, frequent angiogenesis, and enhanced smooth muscle bundle regeneration than the scaffold group. IHC for α-smooth muscle actin, pan-cytokeratin, α-bungarotoxin, and CD8 revealed that the GF group showed high formation of smooth muscle, blood vessel, urothelium, neuromuscular junction and low immunogenicity. Concordantly, real-time polymerase chain reaction experiments revealed that the GF group showed a higher expression of transcripts associated with smooth muscle and urothelial differentiation. In a 6-month in vivo safety analysis, the GF group showed normal histology.

Conclusion: This study showed that a PCL scaffold with a gradient structure incorporating GFs improved bladder regeneration functionally and histologically.

키워드

Bladder Regeneration; Polycaprolactone Scaffold; Gradient Structure; Growth Factors

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