Enhancing colonic anastomotic healing with a novel melatonin-loaded PLGA matrix

Anastomotic leakage continues to be a severe and prevalent complication in colorectal surgery, leading to elevated morbidity and mortality rates despite modern advancements in surgical and perioperative care. To address this persistent clinical challenge, the aim of the present study was to engineer a biocompatible poly(lactic-co-glycolic acid) (PLGA) matrix designed for the sustained release of melatonin, subsequently evaluating its therapeutic efficacy in promoting colon anastomotic repair. Seventy-two male Wistar albino rats were randomly assigned to three experimental groups: anastomosis (n = 24); anastomosis + matrix (n = 24); and anastomosis + melatonin-loaded matrix (n = 24). Anastomotic segments were harvested on postoperative days 3 and 7, and colonic bursting pressure was measured as a functional indicator of anastomotic integrity. The melatonin-loaded matrix significantly enhanced anastomotic healing on postoperative day 7. Melatonin delivery: (1) markedly reduced the gene expression of pro-inflammatory cytokines; (2) modulated iNOS, COX-2 and MPO expression on both days 3 and 7; (3) decreased HO-1 and catalase expression on day 7; (4) promoted collagen synthesis; (5) enhanced collagen deposition through upregulation of Arg-1; and (6) regulated ADAM10 and ADAM17 gene expression. These results are correlated with the histological analysis findings. Collectively, controlled release of melatonin via a PLGA-based biomaterial matrix promotes colon anastomosis healing. This strategy represents a promising translational approach for reducing postoperative anastomotic complications.