Emerging innovations in polycaprolactone-chitosan-hydroxyapatite composite scaffolds for tissue engineering: a review

Polycaprolactone (PCL), chitosan (CS), and hydroxyapatite (HA) have emerged as complementary biomaterials for the design of advanced scaffolds in tissue engineering (TE). Individually, PCL offers excellent mechanical strength and formability but suffers from hydrophobicity and slow degradation. CS provides biocompatibility, antibacterial properties, and favorable cell-material interactions, yet its insufficient mechanical stability limits standalone use. HA, a bioactive ceramic, enhances osteoconductivity; nevertheless, it is brittle in pure form. Recent advances focus on integrating these three components into hybrid composites to harness their desired characteristics. Novel fabrication approaches, including electrospinning and 3D printing have been optimized to tailor scaffold architecture, porosity, and mechanical integrity. Studies highlight enhanced cellular adhesion and differentiation, as well as improved angiogenic and antibacterial performance when functionalized with bioactive agents or nanoparticles. For instance, the incorporation of nano-HA into the PCL/CS scaffolds markedly boosted skin fibroblast cells (HSF 1184) proliferation, yielding a 23% increase compared to PCL/CS scaffolds by day 3. Besides, HA-PCL/CS nanofibrous composite scaffolds demonstrated a marked improvement in mechanical stiffness, showing an increase of greater than 15% in modulus of elasticity compared to the PCL/CS scaffold. Despite these advances, challenges remain in achieving controlled degradation, uniform dispersion of components, and scalable, reproducible fabrication for clinical translation. This current review fills a critical gap by providing the first comprehensive analysis of advancements in PCL-CS-HA ternary TE systems, an area that remains unexplored despite existing reviews on individual materials and their binary combinations. It analyzes latest developments in PCL-CS-HA composites, highlighting their structure, characteristics, processing strategies, biological outcomes, and future directions.