Abstract

The development of curative therapy for bladder dysfunction is usually hampered owing to the lack of reliable ex vivo human models that can mimic the complexity of the human bladder. To overcome this issue, 3D in vitro model systems offering unique opportunities to engineer realistic human tissues/organs have been developed. However, existing in vitro models still cannot entirely reflect the key structural and physiological characteristics of the native human bladder. In this study, we propose an in vitro model of the urinary bladder that can create 3D biomimetic tissue structures and dynamic microenvironments to replicate the smooth muscle functions of an actual human urinary bladder. In other words, the proposed biomimetic model system, developed using a 3D bioprinting approach, can recreate the physiological motion of the urinary bladder by incorporating decellularized extracellular matrix from the bladder tissue and introducing cyclic mechanical stimuli. The results showed that the developed bladder tissue models exhibited high cell viability and proliferation rate and promoted myogenic differentiation potential given dynamic mechanical cues. We envision the developed in vitro bladder mimicry model can serve as a research platform for fundamental studies on human disease modeling and pharmaceutical testing.

Highlights

  • The primary function of the urinary bladder is to store and expel urine by optimizing the intravesical pressure regulated by the detrusor muscle in the bladder wall [1]

  • In 3D bioprinting, using decellularized extracellular matrix (dECM) bioinks can significantly help the production of highly biomimetic tissue constructs by supporting the complex interaction between cells and the microenvironments within the bioprinted tissues [18,29]

  • The urinary bladder smooth muscle is highly responsible for maintaining the bladder contraction and relaxation movements of the bladder, which is essential for the regulation of urination

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Summary

Introduction

The primary function of the urinary bladder is to store and expel urine by optimizing the intravesical pressure regulated by the detrusor muscle in the bladder wall [1]. The smooth muscle cells of the bladder play an essential role in maintaining bladder compliance [2]. Abnormal bladder compliance, such as pathological conditions of the bladder wall, due to abnormal and uncontrollable detrusor contractions leading to slow or incomplete bladder emptying, can cause urinary tract infection, urinary incontinence, and renal failure [3,4]. Precise diagnosis and treating of dysfunctions accurately is still a clinical challenge [5] This can be overcome using a tissue engineering approach, which provides a potential solution for producing a tissue model of the human bladder to realize in vivo bladder functions. It is necessary to develop a reliable model system that closely mimics the physiological and biological features of actual human bladder tissue to support pathological studies pertaining to bladder diseases

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