Preparation of healing promotive alanyl-glutamine-poly(p-dioxanone) electrospun membrane integrated with gentamycin and its application for intestinal anastomosis in rats

Biomater Adv. 2022 Aug:139:212977. doi: 10.1016/j.bioadv.2022.212977. Epub 2022 Jun 6.

Abstract

Anastomosis surgery at the intestinal site is performed on millions of individuals every year. However, several persistent complications, such as anastomotic leakage, abnormal adhesion, and anastomotic stenosis, have been observed after the surgery. For promoting anastomotic healing and to overcome the challenges mentioned above, re-epithelialization at anastomotic sites is crucial. In this study, an epithelialization-promoting macromolecular prodrug Ala-Gln-PPDO was prepared and processed into fibrous membranes by electrospinning. Ala-Gln and gentamicin were sustainably released from the electrospun membranes with degradation of these membranes to promote the proliferation of rat intestinal epithelial cells and suppress the proliferation of Staphylococcus aureus and Escherichia coli. The comprehensive repair effects of Ala-Gln-PPDO membranes have been evaluated in rat models of intestinal anastomosis in this study. Application of Ala-Gln-PPDO membranes, especially the gentamicin-incorporated Ala-Gln-PPDO ones, could prevent adhesion between the injured intestine and surrounding intestinal tissues. In addition, they did not affect the healing strength of anastomotic stoma negatively and could promote re-epithelialization at the anastomotic sites. Furthermore, the gentamicin-incorporated Ala-Gln-PPDO membranes could relieve stenosis at anastomotic sites. The gentamicin-incorporated Ala-Gln-PPDO electrospun membrane is a promising, comprehensive implantable material for promoting healing after gastrointestinal anastomosis owing to its effects involving the promotion of re-epithelialization, prevention of adhesion, and relieving of anastomotic stenosis.

Keywords: Adhesion prevention; Ala-Gln-PPDO; Anastomotic stenosis prevention; Intestinal anastomosis; Re-epithelialization promotion.

MeSH terms

  • Anastomosis, Surgical
  • Animals
  • Constriction, Pathologic / pathology
  • Dioxanes
  • Dipeptides
  • Gentamicins* / pharmacology
  • Intestines* / surgery
  • Polymers
  • Rats
  • Tissue Adhesions / pathology

Substances

  • Dioxanes
  • Dipeptides
  • Gentamicins
  • Polymers
  • poly-4-dioxan-2-one
  • alanylglutamine