Chitosan/hydroxyapatite hydrogels for localized drug delivery and tissue engineering: A review

Abstract

Bone defects arising from fractures and degenerative bone diseases present a substantial global health issue, highlighting the need for effective solutions in bone tissue engineering. Chitosan-hydroxyapatite (CS/HA) composites have emerged as highly promising biomaterials, owing to their biocompatibility, osteoconductive, and suitability for targeted drug delivery. This review examines recent progress in the synthesis, structural properties, and applications of CS/HA composites, along with an analysis of their limitations and potential avenues for enhancement. CS/HA scaffolds are typically fabricated through advanced techniques, including freeze-drying, electrophoretic deposition, and 3D printing. These allow for customized porosity and controlled biodegradation rates that promote cell proliferation and facilitate tissue integration. While effective for non-load-bearing applications, CS/HA hydrogels encounter limitations related to mechanical strength and degradation rates under high-stress conditions, especially when compared to newer materials such as graphene and bioactive glasses. Incorporating bioactive metals (e.g., magnesium, copper) and biodegradable polymers (e.g., PLA, PGA) has shown potential for enhancing mechanical stability and enabling controlled drug release. Additionally, the integration of 3D and 4D printing technologies facilitates the production of patient-specific scaffolds with adjustable pore structures, supporting improved cell adhesion and growth. The development of “smart” CS/HA scaffolds, which respond dynamically to environmental stimuli, further extends the potential for controlled therapeutic agent release, advancing personalized tissue engineering and regenerative medicine. Ongoing research focused on optimizing degradation rates and enhancing scaffold-tissue integration is essential for broadening the clinical applicability of CS/HA composites in bone regeneration. This review underscores the future potential of CS/HA composites and advocates for continued innovation in scaffold design to address the complex requirements of bone tissue engineering.