Influence of the SolubleInsoluble Ratios of Cyclodextrins Polymers on the Viscoelastic Properties of Injectable ChitosanBased Hydrogels for Biomedical Application

Abstract

Injectable pre-formed physical hydrogels provide many advantages for biomedical applications. Polyelectrolyte complexes (PEC) formed between cationic chitosan (CHT) and anionic polymers of cyclodextrin (PCD) render a hydrogel of great interest. Given the difference between water-soluble (PCDs) and water-insoluble PCD (PCDi) in the extension of polymerization, the present study aims to explore their impact on the formation and properties of CHT/PCD hydrogel obtained from the variable ratios of PCDi and PCDs in the formulation. Hydrogels CHT/PCDi/PCDs at weight ratios of 3:0:3, 3:1.5:1.5, and 3:3:0 were elaborated in a double–syringe system. The chemical composition, microstructure, viscoelastic properties, injectability, and structural integrity of the hydrogels were investigated. The cytotoxicity of the hydrogel was also evaluated by indirect contact with pre-osteoblast cells. Despite having similar shear–thinning and self-healing behaviors, the three hydrogels showed a marked difference in their rheological characteristics, injectability, structural stability, etc., depending on their PCDi and PCDs contents. Among the three, all the best above-mentioned properties, in addition to a high cytocompatibility, were found in the hydrogel 3:1.5:1.5. For the first time, we gained a deeper understanding of the role of the PCDi/PCDs in the injectable pre-formed hydrogels (CHT/PCDi/PCDs), which could be further fine-tuned to enhance their performance in biomedical applications.

Chitosan/Polycyclodextrin (CHT/PCD)-Based Sponges Delivering VEGF to Enhance Angiogenesis for Bone Regeneration

“…Chitosan (CHT: batch STBG1894V, M w = 190 kDa, determined by gel permeation chromatography (GPC); degree of deacetylation = 73%, determined by 1 H NMR), lactic acid (LA, >85%) and phosphate buffered saline (PBS, pH 7.4) were purchased from Sigma Aldrich (Saint Quentin, France). Water-soluble cyclodextrin polymer, poly(cyclodextrin citrate) (PCD: M w = 20 kDa, determined by size exclusion chromatography (SEC); %CD content = 58%, determined by NRM) was obtained from the reaction of esterification between β-cyclodextrin (Kleptose ® , Roquette, Lestrem, France) and citric acid (Sigma Aldrich, Saint Quentin, France) acting as cross-linking agent and sodium hypophosphite as catalyst [ 34 , 35 , 36 ]. Recombinant human Vascular Endothelial Growth Factor A-165 (VEGF) was purchased from Promokine (Heidelberg, Germany), and enzyme-linked immunosorbent assay (ELISA) kit for VEGF was obtained from Peprotech (Neuilly-sur-Seine, France).…”

“…First, the CHT and PCD powders (particle size < 125 µm) were co-milled at a ratio of CHT:PCD 3:3 using a mixer mill MM-40 (Retsch ® , Haan, Germany) at 10 Hz for 3 min at room temperature (RT). Then, CHT/PCD hydrogel was obtained using a system of two interconnected syringes as described previously by Palomino-Durand et al [ 34 ]. Briefly, co-milled CHT/PCD powders (6% w/v ) and ultrapure water (93% v/v ), each in a syringe (BD Luer-Lok™, Le Pont de Claix, France), were thoroughly mixed by pressing alternately on the plungers for 1 min.…”

“…After incubation, the nutrient-deficient medium was replaced with the VEGF release medium collected from the VEGF release process described above, and the plate was incubated for 48 h. A positive control (50 ng/mL VEGF) and a negative control (ECM medium supplemented with 0.1% FBS) were also tested. The proliferation of the cells was finally quantified by a fluorometric assay with AlamarBlue ® reagent (Gibco ® , Thermo Fisher Scientific, Illkirch-Graffenstaden, France) [ 34 ].…”

“…The combination of PCD and CHT allows the formation of PEC hydrogels. The application of these injectable CHT-PCD hydrogels for drug delivery in wound dressing [ 33 ] and tissue engineering [ 34 ] were recently reported by our team.…”

History of cyclodextrin-based polymers in food and pharmacy: a review

“…Hydroxyapatite used in bone implants can also be functionalized with a cyclodextrin polymer for loading antibiotics (Hoang Thi et al 2010 ; Taha et al 2014 ). Recently, injectable hydrogels of polyelectrolyte complexes between chitosan and cyclodextrin polymers have been rheologically tested (Palomino-Durand et al 2019 ).…”