Exploration of a new method of a biopatch based on the central concept of the multi-layer repair

Abstract

This letter discusses the findings of Pang et al retrospective study on omental patch repair as a balanced treatment for gastric ulcer perforation. We acknowledge its clinical value while highlighting a critical limitation: Conventional mechanical closure often results in fibrotic scarring and functional impairment across the mucosal, muscular, and neurovascular layers. To address this, we propose the innovative concept of “multi-layer repair” and present a proof-of-concept three-dimensional bioprinted functional biopatch. This patch features a multilayer structure: An inner layer laden with gastric mucosal organoids and an outer layer containing primary gastric muscle cells, both integrated onto a wet-adhesive electrospun membrane. Preliminary animal studies have yielded encouraging results, supporting its potential to promote functional restoration beyond mechanical sealing.

Key Words: Gastric perforation; Omental patch; Surgery; Biopatch; Hydrogel

Core Tip: We propose a novel “multi-layer repair” concept addressing the limitations of traditional omental patch repair for gastric ulcer perforation. Utilizing three-dimensional bioprinting technology, we engineered a biologically functional patch that recapitulates native gastric layering: An inner mucosal organoid-containing region and an outer smooth muscle cell layer. Preliminary results from animal studies indicated that this approach, which aimed to restore physiological structural-functional coupling of the stomach, appears to facilitate a repair that extends beyond mere mechanical closure, showing promise for achieving true anatomical and functional recovery.

TO THE EDITOR

We have read the retrospective study by Pang et al[1] which evaluating the efficacy and postoperative complications among different surgical methods for gastric ulcer perforation. This article incorporated patients underwent surgeries like simple closure, omental patch repair and partial gastrectomy for gastric ulcer perforation, then analyzed the operative success rate and the incidence of complications. The authors indicated that omental patch repair offered the best balance of efficacy, safety, and recovery time. Omental patch repair can reduce the abnormal organ function caused by partial loss of organs, which may be most useful in large perforations with friable tissue[2], it reflects an optimal balance between effective treatment and minimal disruption of normal anatomy and physiology.

Gastric ulcer perforation is a life-threatening complication of peptic ulcer disease which is the most common indication for surgery in peptic ulcer disease[2]. Although traditional surgery is the mainstay, emerging minimally invasive techniques such as laparoscopic-assisted endoscopic overstitch technique[3], hydrogel bioadhesives for minimally invasive perforation repair[4], compressible and expandable hemostatic structural pattern[5], among others, are gaining attention.

Nevertheless, purely mechanical closure often fails to restore structural-functional integrity, which can lead to the formation of fibrous scars at the perforation site, resulting in the loss of essential functions in the mucosal layer, muscular layer, and neurovascular structures at the gastric repair site. This thereby causes abnormal gastric contraction rhythms and impairs the gastric mucosal barrier function. To address this, we propose “multilayer repair” as a regenerative strategy aimed at replicating native gastric anatomy and function. While previous studies have explored multilayer tissue constructs using organ-derived decellularized extracellular matrix hydrogels such as the heart, aorta, lung, and skin[6,7], our approach focuses on gastric-specific repair through biofabrication. This concept emphasizes the physiological layering of the gastrointestinal tract, incorporating precise anastomosis of tissue strata, preservation of neurovascular supply, and inhibition of fibroblast overactivation[8].

Our team fabricated a functional biopatch based on the central concept of the multi-layer repair. The biopatch, J@PVP-PCL via electrospinning, was a core-sheath structured wet adhesive with polyurethane as the core and polyvinylpyrrolidone as the sheath, combined with a hydrophobic polycaprolactone layer. Onto this, we attempted to print a multi-layer hydrogel loaded with cells, where the mucosal layer contains gastric mucosal organoids, and the outer layer has primary gastric muscle cells, and can be attached to the wet-adhesive electrospinning fiber membrane (Figure 1).

The core zone was constructed by three-dimensional bioprinting, comprising: A bottom layer of 8% gelatin methacryloyl (GelMA) infused with primary gastric smooth muscle cells (at a density of 1 × 10⁶ cells per milliliter of GelMA); a top layer of 8% GelMA incorporated with gastric epithelial organoids (at a density of 1000 organoids per milliliter of GelMA). It has achieved certain results in animal experiments. We made a 1-cm gastric wound in a porcine model and then collected endoscopic view of the repair site at 2 weeks after applying the biopatch (Figure 2). This patch utilizes a biological mesh framework to attempt multi-layer repair of full-thickness gastric defects, which is expected to facilitate multi-layer repairs such as the repair of gastric ulcer perforation. However, larger animal models are needed to verify this, and in the future, digestive endoscopic delivery will be explored to promote wound closure and repair.

Figure 1 Gross image of the three-dimensional-printed product.

Figure 2 Endoscopic view of the repair site at 2 weeks after applying the biopatch onto a 1-cm gastric wound in a porcine model.