ABSTRACT
Polypropylene meshes are standard for hernia repair. Matrix metalloproteinases play a central role in inflammation. To reduce the inflammatory response and improve remodelling with an associated reduction of hernia recurrence, we modified polypropylene meshes by nanofibre coating and saturation with the broad-spectrum matrix metalloproteinase inhibitor GM6001. The aim was to modulate the inflammatory reaction, increase collagen deposition and improve mesh biointegration. Polypropylene meshes were surface-modified with star-configured NCO-sP(EO -stat-PO) and covered with electrospun nanofibres (polypropylene-nano) and GM6001 (polypropylene-nano-GM). In a hernia model, defects were reconstructed with one of the meshes. Inflammation, neovascularization, bio-integration, proliferation and apoptosis were assessed histologically, collagen content and gelatinases biochemically. Mesh surface modification resulted in higher inflammatory response compared to polypropylene. Pro-inflammatory matrix metalloproteinase-9 paralleled findings while GM6001 reduced matrix metalloproteinase-9 significantly. Significantly increased matrix metalloproteinase-2 beneficial for remodelling was noted with polypropylene-nano-meshes. Increased vascular endothelial growth factor, neo-vascularization and collagen content were measured in polypropylene-nano-meshes compared to polypropylene. GM6001 significantly reduced myofibroblasts. This effect ended after d14 due to engineering limitations with release of maximal GM6001 loading. Nanofibre-coating of polypropylene-meshes confers better tissue vascularization to the cost of increased inflammation. This phenomenon can be only partially compensated by GM6001. Future research will enable higher GM6001 uptake in nano-coated meshes and may alter mesh biointegration in a more pronounced way.
Subject(s)
Coated Materials, Biocompatible/chemistry , Dipeptides/administration & dosage , Herniorrhaphy , Matrix Metalloproteinase Inhibitors/administration & dosage , Surgical Mesh , Wound Healing/drug effects , Abdominal Wall/surgery , Animals , Collagen/analysis , Collagen/metabolism , Dipeptides/pharmacology , Dipeptides/therapeutic use , Drug Delivery Systems , Hernia , Herniorrhaphy/methods , Male , Matrix Metalloproteinase 2/analysis , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/analysis , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase Inhibitors/pharmacology , Matrix Metalloproteinase Inhibitors/therapeutic use , Nanofibers/chemistry , Nanofibers/ultrastructure , Neovascularization, Physiologic/drug effects , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Polypropylenes/chemistry , Rats, Sprague-DawleyABSTRACT
BACKGROUND: In order to allow inflammatory response modification and ultimately improvement in tissue remodeling, we developed a new surface modification for meshes that will serve as a carrier for other substances. Biocompatibility is tested in an animal model. METHODS: The animal model for diaphragmatic hernia repair was established in prior studies. Meshes were surface modified with star-configured PEO (polyethylene oxide)-based molecules [sP(EO-stat-PO)]. An electrospun nanoweb of short-term absorbable PLGA (polylactide-co-glycolide) with integrated sP(EO-stat-PO) molecules was applied onto the modified meshes. This coating also served as aerial sealing of the diaphragm. A final layer of hydrogel was applied to the product. Adhesive properties, defect size and mesh shrinkage were determined, and histological and immunohistochemical investigations performed after 4 months. RESULTS: The mean defect size decreased markedly in both modified mesh groups. Histologically and with regard to apoptosis and proliferation rate, smooth muscle cells, collagen I/III ratio and macrophage count, no statistically significant difference was seen between the 3 mesh groups. CONCLUSIONS: In this proof-of-principle investigation, we demonstrate good biocompatibility for this surface-modified mesh compared to a standard polypropylene-based mesh. This new coating represents a promising tool as a carrier for bioactive substances in the near future.
