Ferdowsi University of Mashhad

Smart Chitosan-based Scaffolds for Cartilage Regeneration: From Biomaterial Design to Clinical Applications

Document Type : Review / Mini-Review

Authors

1 Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

2 Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran

Abstract
Treatment of cartilage injuries remains a crucial clinical challenge due to the intrinsically limited capacity of this tissue for regeneration. Common treatment approaches are often unable to restore the natural structure and the long-term function of articular cartilage. Therefore, tissue engineering emerges as a promising approach that enhances cartilage regeneration using cell integration, scaffolds, and bioactive molecules. Chitosan stands out among various types of bioactive materials owing to its biocompatibility, biodegradability, anti-inflammatory effects, and structural similarity to cartilage extracellular matrix, glycosaminoglycans. This review investigates recent developments in the design and application of chitosan scaffolds in cartilage tissue engineering. Various scaffold formats, including hydrogels, porous and nanofibrous structures, as well as three‑dimensional printed constructs, have been shown to support the proliferation, adhesion, and differentiation of chondrocytes. On the other hand, chitosan carriers have been developed for the controlled release of growth factors, anti-inflammatory drugs, and nucleic acids, enhancing the tissue regeneration results. Engineering strategies such as chemical modification, combination with natural or synthetic polymers, and incorporation of bioactive molecules lead to improved mechanical strength, bioactivity, and immunomodulatory properties of chitosan-based scaffolds. Preclinical studies in animal models followed by initial clinical trials and subsequent production of commercial products present promising evidence of the clinical translatability of chitosan scaffolds. Recent innovations, including responsive smart scaffolds and 4D bioprinting, show that scaffolds are transitioning from static biomaterials toward dynamic structures with compatibility in physiologic environments. Overall, chitosan provides a multipurpose and promising biomaterial for cartilage regeneration. The continuation of interdisciplinary research, along with advancements in customized modeling, can accelerate the development of new-generation scaffolds, ultimately leading to improved long-term clinical outcomes.
 

Keywords


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Volume 17, Issue 1 - Serial Number 33
September 2025
Pages 20-40

  • Receive Date 02 September 2025
  • Revise Date 03 September 2025
  • Accept Date 05 September 2025