Hydrogel scaffolds in tissue engineering for urethral repair and reconstruction

Abstract

BACKGROUND: In recent years, hydrogel scaffolds, as important carriers in the field of tissue engineering, have made significant progress in their application in urethral repair and reconstruction. OBJECTIVE: To systematically review the design strategies of urethral tissue engineering scaffolds, the functional modification of hydrogel scaffolds, and their application progress in urethral repair, and to explore the future development directions and clinical transformation challenges of hydrogel scaffolds. METHODS: The CNKI and PubMed databases were searched using Chinese and English keywords "hydrogel, tissue engineering scaffold, urethral tissue engineering, urethral repair, urethral reconstruction." Based on the inclusion criteria, 69 articles were finally selected for inductive analysis. RESULTS AND CONCLUSION: In urethral tissue engineering, urethral scaffolds should not only possess basic characteristics such as biocompatibility but also exhibit unique properties that adapt to the structure of the urethra and the urinary environment. Hydrogel scaffolds can be classified into natural hydrogel scaffolds (commonly protein-based, polysaccharide-based, DNA-based, and extracellular matrix-based) and synthetic polymer hydrogel scaffolds (commonly polyvinyl alcohol, polyacrylic acid, acrylate-based). Crosslinking methods mainly include physical and chemical crosslinking, and preparation methods include in situ gelation, freeze-drying, electrospinning, and 3D bioprinting. To avoid the drawbacks of single materials, composite hydrogel scaffolds are often used in urethral tissue engineering, such as composite scaffolds adapted to the urethral microenvironment, composite scaffolds utilizing decellularized extracellular matrix, multilayer composite scaffolds loaded with stem cells, and non-stem cell-based hydrogel scaffolds. With the development of tissue engineering and regenerative medicine, future hydrogel scaffolds should be designed with intelligent, engineered, and cell-free strategies, while considering current clinical translation barriers and proposing comprehensive solutions.

1. Introduction

The urethra, as an internal structure of the human body, is a conduit connecting the bladder to the exterior. Its core function is to transport urine, and in males, it also serves to transport semen during reproduction. In urology, various pathological factors can lead to urethral injury, adversely affecting patients' quality of life. Among these, congenital urethral defects (e.g., hypospadias) and acquired urethral abnormalities (e.g., urethral stricture) are the most common [1]. Urethroplasty is the primary surgical treatment for hypospadias and urethral stricture, but postoperative complications are frequent, including fistulas, strictures, and dehiscence or recurrence after aponeurotic repair [1]. The continuous advancement of tissue engineering offers new possibilities for urethral repair and reconstruction, potentially overcoming the limitations of current treatments and improving surgical outcomes [2].

Tissue engineering is an interdisciplinary field that integrates biology, materials science, medicine, and engineering to provide novel techniques and therapeutic strategies for tissue and organ regeneration [2]. The core of tissue engineering is the construction of a three-dimensional complex composed of cells and biomaterials. These biomaterials not only promote the ingrowth of surrounding tissues and cells but also serve as temporary scaffolds for cell adhesion, proliferation, and differentiation. A key aspect is the development of biomimetic scaffolds to facilitate tissue regeneration, and hydrogels, with properties highly similar to the natural extracellular matrix, have become ideal carriers for this purpose [3].

Hydrogels are water-swollen three-dimensional polymer networks with tunable physicochemical properties that can be tailored to specific requirements. As promising materials, hydrogels are widely used in biomedical fields, ranging from physiological and pathological mechanism studies to tissue regeneration and disease treatment [4]. The core structure of hydrogels is a crosslinked polymer network [5], characterized by high hydrophilicity, high water content (up to 99.5%), extensibility, and biocompatibility close to living tissues [6-7]. These attributes make hydrogels ideal candidate materials for urethral tissue engineering scaffolds. This review aims to summarize the research achievements of hydrogel scaffolds in tissue-engineered urethral repair and reconstruction, and to discuss future development directions and challenges in clinical translation.