In Vitro and In Vivo Cell-Interactions with Electrospun Poly (Lactic-Co-Glycolic Acid) (PLGA): Morphological and Immune Response Analysis

Abstract

Random electrospun three-dimensional fiber membranes mimic the extracellular matrix and the interfibrillar spaces promotes the flow of nutrients for cells. Electrospun PLGA membranes were analyzed in vitro and in vivo after being sterilized with gamma radiation and bioactivated with fibronectin or collagen. Madin-Darby Canine Kidney (MDCK) epithelial cells and primary fibroblast-like cells from hamster’s cheek paunch proliferated over time on these membranes, evidencing their good biocompatibility. Cell-free irradiated PLGA membranes implanted on the back of hamsters resulted in a chronic granulomatous inflammatory response, observed after 7, 15, 30 and 90 days. Morphological analysis of implanted PLGA using light microscopy revealed epithelioid cells, Langhans type of multinucleate giant cells (LCs) and multinucleated giant cells (MNGCs) with internalized biomaterial. Lymphocytes increased along time due to undegraded polymer fragments, inducing the accumulation of cells of the phagocytic lineage, and decreased after 90 days post implantation. Myeloperoxidase+ cells increased after 15 days and decreased after 90 days. LCs, MNGCs and capillaries decreased after 90 days. Analysis of implanted PLGA after 7, 15, 30 and 90 days using transmission electron microscope (TEM) showed cells exhibiting internalized PLGA fragments and filopodia surrounding PLGA fragments. Over time, TEM analysis showed less PLGA fragments surrounded by cells without fibrous tissue formation. Accordingly, MNGC constituted a granulomatous reaction around the polymer, which resolves with time, probably preventing a fibrous capsule formation. Finally, this study confirms the biocompatibility of electrospun PLGA membranes and their potential to accelerate the healing process of oral ulcerations in hamsters’ model in association with autologous cells.

Surface Modification Progress for PLGA-Based Cell Scaffolds

“…Furthermore, these cell arrangements were similar to the structural characteristics of dense and soft connective tissues, respectively. Long-term transplantation experiments in animals showed good biocompatibility [ 13 ], thus suggesting that FN-coated PLGA scaffolds have the potential to promote the healing of wounds.…”

“…As a result, functional coatings have been applied on PLGA scaffolds to increase cell adhesion and viability. These coating materials include polymers such as polyethylene glycol (PEG) [ 7 ], polydopamine (PDA), polypyrrole (Ppy) [ 8 ], poly-lysine [ 9 ], polyethyleneimine (PEI) [ 10 ], and ECM components such as HA [ 11 ], laminin [ 12 ], FN [ 13 ], and collagen [ 14 ]. Studies have shown that modifying PLGA-based scaffolds with these materials could improve the hydrophilicity and cell adhesion on PLGA.…”

Fibrous hydrogels by electrospinning: Novel platforms for biomedical applications

“…Typically, diameters of electrospun fibers, controlled by electrospinning setup (voltage applied to a needle, flow rate of precursors, and distance between a needle and a collector) 32 – 35 and viscosity of precursors, 36 vary from some 10 nm to 10 µm, 37 and various approaches (rotating collector, gap electrospinning, and magnetic field-assisted electrospinning) were developed to manipulate alignment of fibers. 38 – 41 These micro/nanofibers were electrospun with various materials such as poly (ε-caprolactone) (PCL), 42 – 44 polylactic acid (PLA), 45 , 46 poly (D, L-lactic-co-glycolic) acid (PLGA), 47 – 50 polyurethane (PU), 51 – 53 and polyacrylonitrile (PAN) 54 , 55 and used for drug delivery, wound dressings, and vascular graft applications.…”