Chitosan-hydroxyapatite composite hydrogels for bone regeneration

Abstract

Event Abstract Back to Event Chitosan-hydroxyapatite composite hydrogels for bone regeneration Claudia Flores1, Marco Lopez1, Jean-Christophe Hornez2, Feng Chai1, Gwenael Raoul1, 3, Nicolas Tabary4, Frederic Cazaux4, Joel Ferri1, 3, Frederic Hildebrand1, Bernard Martel4 and Nicolas Blanchemain1 1 University of Lille, INSERM U1008 - Biomaterial Research Group, France 2 University of Valenciennes Hainaut Cambrésis, LMCPA EA2443, France 3 Roger Salengro Hospital, CHU Lille, Maxillofacial Surgery and Stomatology Department, France 4 University of Lille, UMET, CNRS UMR 8207 Polymer Systems Engineering, France Introduction: Bone is a composite that possess an inorganic hydroxyapatite (HA) and an organic extracellular matrix (ECM) part [1]. A composite material stands as an appropriate substitute for bone regeneration. This work aims to elaborate and characterize a novel composite hydrogel based on chitosan (CHT), a cationic polymer that can mimic the ECM [2]; cyclodextrin polymer (PCD), an anionic polymer with excellent drug delivery properties [3] and HA, in order to highlight its properties for cell colonization. Materials and Methods: Composite CHT-PCD-HA hydrogels were obtained by mixing CHT (3% w/v), PCD (3% w/v) and HA (3% w/v) with acetic acid solution (AA, 1% v/v) or hydrochloric acid (0.1M HCl) [4]. Gelation time was evaluated by measuring G’ (storage modulus) and G’’ (loss modulus) with a rheometer. The hydrogel charge was evaluated by zeta potential (ZP) measurement. The pH was also monitored during the gelation. Hydrogels were freeze-dried to obtain a xerogel. The morphology and chemical properties of gels were studied respectively by scanning electron microscopy and FTIR spectroscopy. The cytocompatibility of xerogel was assessed (ISO 10993-5) with osteoblasts (MC3T3-E1). Their drug carrying and delivery capacity was investigated by impregnation in ciprofloxacin (CFX, Kabi®, 2 mg/mL); the release profile was determined under dynamic conditions at 37°C in phosphate buffered saline (PBS). Their antibacterial activity was determined against E. coli and S. aureus by using the Kirby Bauer test. Results and Discussion: The type of acid and its concentration had an effect on the pH evolution during the gelation of the hydrogels due to the interaction between the cationic (CHT) and the anionic (PCD) polymer. The pH directly affected the consistency, cohesion, as well as the gelation time of the hydrogels [5]. The ZP indicated that the acidic environment influenced the charge of the CHT component, which may be also related to the pH evolution and gelation time. No evident difference was found for the morphology. The major difference for the chemical bonds was observed after the interaction of CHT and PCD. Low pH in the hydrogel provoked certain cytotoxicity in vitro; however, a neutralization treatment and/or dynamic conditions could reduce this cytotoxicity [6, 7]. Loaded CFX was released progressively in a sustainable manner in PBS at 37°C up to 24 hours. The antibacterial activity of this xerogel was maintained during 72 hours against E. coli and S. aureus. Conclusion: Novel composite CHT-PCD-HA hydrogels, and their xerogels, i.e. after freeze-drying, based on the physical ionic interaction between CHT and PCD were obtained. The initial acidic environment played a significant role on the electrostatic charge of CHT and gelation phenomenon. The composite CHT-PCD-HA hydrogel presented good injectability and cohesion properties; its xerogel was cell friendly and offered a promising sustained drug delivery which showed a good potential to be used as a drug delivery vector as well as a bone substitute material. The authors thank Prof. Betbeder for the zeta potential measurements and the Nord-Pas-de-Calais region for their financial support in Arcir BIOCERMED