A novel route for the production of chitosan/poly(lactide-co-glycolide) graft copolymers for electrospinning

Abstract

Both chitosan and polylactide/polyglycolide have good biocompatibility and can be used to produce tissue engineering scaffolds for cultured cells. However the synthetic scaffolds lack groups that would facilitate their modification, whereas chitosan has extensive active amide and hydroxyl groups which would allow it to be subsequently modified for the attachment of peptides, proteins and drugs. Also chitosan is very hydrophilic, whereas PLGA is relatively hydrophobic. Accordingly there are many situations where it would be ideal to have a copolymer of both, especially one that could be electrospun to provide a versatile range of scaffolds for tissue engineering. Our aim was to develop a novel route of chitosan-g-PLGA preparation and evaluate the copolymers in terms of their chemical characterization, their performance on electrospinning and their ability to support the culture of fibroblasts as an initial biological evaluation of these scaffolds. Chitosan was first modified with trimethylsilyl chloride, and catalyzed by dimethylamino pyridine. PLGA-grafted chitosan copolymers were prepared by reaction with end-carboxyl PLGA (PLGA-COOH). FT-IR and(1)H-NMR characterized the copolymer molecular structure as being substantially different to that of the chitosan or PLGA on their own. Elemental analysis showed an average 18 pyranose unit intervals when PLGA-COOH was grafted into the chitosan molecular chain. Differential scanning calorimetry results showed that the copolymers had different thermal properties from PLGA and chitosan respectively. Contact angle measurements demonstrated that copolymers became more hydrophilic than PLGA. The chitosan-g-PLGA copolymers were electrospun to produce either nano- or microfibers as desired. A 3D fibrous scaffold of the copolymers gave good fibroblast adhesion and proliferation which did not differ significantly from the performance of the cells on the chitosan or PLGA electrospun scaffolds. In summary this work presents a methodology for making a hybrid material of natural and synthetic polymers which can be electrospun and reacts well as a substrate for cell culture.

Electrospun hydroxyapatite-containing chitosan nanofibers crosslinked with genipin for bone tissue engineering

“…Analysis of SEM micrographs (Figure 2), revealed a mean fiber diameter of 335±119 nm for CTS-GP scaffolds. This large variability and heterogeneity in the size of electrospun CTS nanofibers has been described before and may be due to inhomogeneity of the solution [24, 28, 49]. CTS has an extremely high surface tension and requires harsh solvents, such as TFA for appropriate fiber formation upon electrospinning [45].…”

“…Chitosan (CTS) [14–16], the deacetylated form of chitin, a polysaccharide derived from the exoskeleton of crustaceans [17] has emerged as a promising candidate for bone tissue engineering, mainly due to its biocompatibility and structural similarity to bone ECM [18, 19]. Recent approaches focus on co-electrospinning CTS with other materials, such as collagen, poly(lactic-co-glycolic acid) (PLGA) and poly(caprolactone) (PCL) for a variety of applications, including that of engineering functional bone scaffolds [13, 20–24]. However, little attention has been paid to generating fibrous chitosan-based scaffolds which combine the physical properties of cortical bone and the mechanical and conductive properties of the periosteum, the layer of bone that is responsible for the success of autografts over allografts and engineered constructs [8].…”

Functionalizing PLGA and PLGA Derivatives for Drug Delivery and Tissue Regeneration Applications

“…These polymers are highly hydrophilic, and thus they are not able to melt and are insoluble in a considerable range of organic solvents. [70] Therefore, this restricts the methodology of production of polysaccharides-PLGA copolymers and excludes the performance of ROP, among other methods. [71] The synthesis of the copolymer of PLGA and CS, the PLGA-CS, is usually carried out by the reaction of the activated acid-terminated PLGA with the amine groups of CS.…”

Investigation of Human Mesenchymal Stromal Cells Cultured on PLGA or PLGA/Chitosan Electrospun Nanofibers

“…Reports in the literature have noted the potential application of PLGA/CH nanofibrous scaffolds for wound healing and skin tissue reconstruction [37][38][39]. However, no study has been carried out thus far to investigate the interaction of MSC with this hybrid scaffold.…”