Design and Evaluation of a Crosslinked Chitosan-Based Scaffold Containing Hyaluronic Acid for Articular Cartilage Reconstruction

用于关节软骨重建的含透明质酸的交联壳聚糖基支架的设计与评价

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Abstract

Polymeric scaffolds are promising in tissue engineering due to their structural similarity to extracellular matrix components. This study aimed to design freeze-dried hydrogels based on chitosan (CHT) and hyaluronic acid (HA). Chitosan-based gels were crosslinked with oxidized maltodextrin (MDo) before the freeze-drying step, resulting in spongy porous scaffolds. Based on the state-of-the-art, our hypothesis was that crosslinking would increase scaffold stiffness and delay the degradation of the CHT:HA resorbable scaffolds swelled in a hydrated physiological environment. The physicochemical and mechanical properties of crosslinked CHT- and CHT:HA-based scaffolds were analyzed. Hygroscopic and swelling behavior were assessed using dynamic vapor sorption analysis and batch studies. Degradation was evaluated under different conditions, including in phosphate-buffered saline (PBS), PBS with lysozyme, and lactic acid solutions, to investigate scaffold resistance against enzymatic and acidic degradation. The porosity of the spongy materials was characterized using scanning electron microscopy, while dynamic mechanical analysis provided information on the mechanical properties. Crosslinked scaffolds showed reduced swelling, slower degradation rates, and increased stiffness, confirming MDo as an effective crosslinking agent. Scaffolds loaded with ciprofloxacin (CFX) demonstrated their ability to deliver therapeutic agents, as the CFX loading capacity was promoted by CHT-CFX interactions. Microbiologic investigation confirmed the results. Finally, cytotoxicity tests displayed no toxicity. In conclusion, MDo-crosslinked CHT and CHT:HA scaffolds exhibit enhanced stability, functionality, and mechanical performance, making them promising for cartilage tissue engineering.

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