Bioengineered Approaches for Esophageal Regeneration: Advancing Esophageal Cancer Therapy

Abstract

Esophageal cancer (EC) is the eighth leading cause of cancer-related deaths globally, largely due to its late-stage diagnosis and aggressive progression. Esophagectomy remains the primary treatment, typically requiring organ-based reconstruction techniques such as gastric pull-up or colonic interposition. However, these reconstruction methods often lead to severe complications, significantly reducing the quality of life of patients. To address these limitations, tissue engineering has emerged as a promising alternative, offering bioengineered patch-type and tubular-type scaffolds designed to restore both structural integrity and functional regeneration. Recent advancements in three-dimensional (3D) biofabrication-including 3D bioprinting, electrospinning, and other cutting-edge techniques-have facilitated the development of patient-specific constructs with improved biocompatibility. Despite significant advancements, critical challenges persist in achieving mechanical durability, multilayered cellular organization, and physiological resilience post-transplantation. Ongoing research continues to address these limitations and enhance clinical applicability. Therefore, this review aims to examine recent advancements in esophageal tissue engineering, with a focus on key biofabrication techniques, preclinical animal models, and the major translational challenges that must be addressed for successful clinical application.

Keywords: animal models; esophageal cancer; esophageal reconstruction; patch-type scaffolds; tissue engineering; tubular-type scaffolds.

Figure 4

Patch-type scaffolds for esophageal tissue engineering. (A) SEM images of electrospun bilayer matrices (EL-Ms) and temperature-induced precipitation films (TIP-Fs). Reproduced under the Creative Commons Attribution 4.0 International license (CC-BY) [76]. (B) Design of a study for a bioactive and biodegradable bilayer mesh-based scaffold. Reproduced under the CC-BY 4.0 license [78]. (C) Bright-field and fluorescence images of an anisotropic smooth muscle patch fabricated using 3D printing. Reproduced under the CC-BY 4.0 license [82].

Figure 1

Overview of the main topics covered in this review: clinical overview of esophageal cancer, current clinical strategies and limitations, recent advances in esophageal tissue engineering, animal models for esophageal tissue engineering, and future challenges and perspectives related to esophageal regeneration strategies.

Figure 2

Trends in publication counts from 1990 to 2023 on esophageal regenerative and reconstructive approaches, including esophageal reconstruction surgery, esophageal transplantation surgery, esophageal tissue engineering, and bioprinting. Data were compiled and analyzed by the author using Google Scholar search results.

Figure 3

Schematic overview of surgical limitations and tissue engineering solutions for esophageal reconstruction.