Multimodal Evaluation of the Anti-Adhesion Effects of Heparin-Loaded PLGA/HA Nanofiber Membranes in an Intraperitoneal Adhesion Model in Rats

Objective: This study aimed to produce and characterize nanofiber membranes (PLGA/HA@LMWH) containing Poly(lactic-co-glycolic acid)/Hyaluronic Acid (PLGA/HA) immobilized with low molecular weight heparin (LMWH), and to investigate their physical and chemical effects in preventing intraabdominal adhesions in a rat model using multidisciplinary methods. Materials and Methods: Forty female Wistar Albino rats were divided into four groups (n=10). Cecal abrasions were induced in three groups: treated with PLGA/HA membrane (NFM), PLGA/HA@LMWH membrane (NFM+H), and 0.9% NaCl (SS). The fourth group underwent laparotomy only. On day 21, rats were sacrificed and evaluated macroscopically, histopathologically, immunohistochemically, and biochemically. Results: Macroscopic adhesion, inflammation, fibrosis, neovascularization, collagen scores, and TGF-β1 expression were found to be high in the SS and NFM groups; while a significant decrease (p < 0.05–0.01) was detected in all of these values in the NFM+H group. NF-κB activation was significantly decreased in the NFM and especially the NFM+H groups compared to the SS group (p < 0.05). In addition, apoptosis was suppressed in the NFM+H group with increased Bcl-2 and decreased cleaved caspase-3. Conclusion: PLGA/HA@LMWH membrane reduced peritoneal adhesions by suppressing inflammation, fibrosis, neovascularization, and collagen deposition, lowering TGF-β1 expression and NF-κB and p-NF-κB levels, and suppressing apoptosis. However, large-scale studies are needed for clinical use.