Basic fibroblast growth factor-loaded hydrogel biomaterial patches for promoting the healing of esophageal anastomosis: an experimental animal study

Abstract

Background: The management of esophageal anastomotic fistula continues to be a significant clinical challenge in the field of esophageal surgery. With rapid advances in material science, selecting appropriate biomaterials to enhance anastomotic healing and reduce the incidence of anastomotic fistula has emerged as a promising strategy to address the issues. The aim of this study was to investigate the prevention of anastomotic fistula by reinforcing the anastomosis with suitable biomaterial patches.

Methods: Forty large, healthy adult New Zealand white rabbits were randomized into the experimental group (n=20) and the control group (n=20). An animal model of cervical esophageal anastomosis was established using the esophagectomy anastomosis method. The esophageal anastomoses of the rabbits in the experimental group were completely covered with hydrogel biomaterial patches loaded with basic fibroblast growth factor (bFGF) intraoperatively. Four weeks after surgery, the incidence of anastomotic fistula was observed, and tissue samples were obtained from the esophageal anastomosis site for histologic and immunofluorescent detection.

Results: An animal model of cervical esophageal incision and anastomosis was successfully established in rabbits, and the incidence of anastomotic fistula in the experimental group was lower than that in the control group at the end of the experiment (1/18 versus 7/19; P<0.05). The esophageal anastomosis tensile test showed that the anastomosis in the experimental group had higher mechanical strength than that in the control group (6.49±0.17 versus 6.33±0.12 N; P<0.05). Histological examination of the anastomotic specimens showed that the tissue layers of the esophageal anastomoses in the experimental group were clear, and fibroblast proliferation and collagen fiber secretion were greater than those in the control group. Immunofluorescence showed that fibroblast proliferation was significantly increased in the perianastomotic tissues of the experimental group compared to that of the control group.

Conclusions: The application of hyaluronic acid methacrylate (HAMA) hydrogel biomaterial patches loaded with bFGF in esophageal surgery improved the mechanical strength of the esophageal anastomosis, facilitated fibroblast proliferation and collagen secretion, and could promote the growth of the tissues around the esophageal anastomosis. It may thus serve as a novel therapeutic approach for reducing the incidence of anastomotic fistula in esophageal cancer.

Keywords: Biomaterial patches; anastomotic fistula; esophageal cancer; fibroblast growth factor.

Figure 1

The biomaterial patch.

Figure 2

The control group without patches and the experimental group with the biomaterial patch.

Figure 3

Severe anastomotic fistula in the experimental group.

Figure 4

Anastomotic fistulas in the control group. (A) The anastomosis healing well. (B-D) Severe anastomotic fistula causing death. (E-H) Limited anastomotic fistula.

Figure 5

HE staining and Masson staining. (A,C) Anastomoses without patches. (B,D) Anastomoses with the biomaterial patch. Red arrows indicate the biomaterial patch. HE, hematoxylin-eosin.

Figure 6

Immunofluorescence staining. (A) The anastomosis without a patch. (B) The anastomosis with the biomaterial patch.

Figure 7

Comparison of anastomotic healing. Left panel: well-healed anastomosis with the biomaterial patch. (A,C) Anastomosis with the biomaterial patch. (B,D) Anastomoses without patches; significant hyperplasia at the esophageal anastomosis was visible in the experimental group as compared with the control group.

Figure 8

The small size of the biomaterial patches resulted in limited diastole at the anastomosis. The cephalic esophagus was significantly more dilated than was the caudal esophagus. White arrow indicates the biomaterial patch.