Development of Injectable and Self-Healing Gelatin/Dextran/Tannic Acid Composite Hydrogels Incorporating PCL/β-Tricalcium Phosphate Microspheres for Bone Tissue Regeneration.

Abstract

The current study introduces a novel hybrid system of polycaprolactone-nano beta-tricalcium phosphate microspheres (PCL-β-TCP Ms) combined with a hydrogel, which acts as a bone scaffold to accelerate osteogenic capabilities. This innovative system comprises a gelatin (Gel), oxidized dextran (Odex), and tannic acid (TA) hydrogel that integrates PCL-β-TCP microspheres. The Schiff base reaction between Gel and Odex, and the hydrogen bonding interaction of tannic acid and polymers, developed the hydrogel substrate. The process of fabricating the β-TCP-encapsulated PCL microspheres involved using the emulsion solvent evaporation technique, a method that allows for the encapsulation of bioactive substances within the microspheres. The findings revealed that incorporating microsphere-encapsulated β-TCP into the hydrogels notably enhanced their rheological properties, contributing to improved flow behavior and structural integrity. Additionally, the scanning electron microscopy (SEM) images illustrate that the addition of tannic acid leads to the development of a prominent fibrous structure within the hydrogels. This structural enhancement indicates that the presence of tannic acid plays a crucial role in modifying the hydrogel's composition at a microscopic level. The study investigated the interactions between biological cells and hybrid hydrogels in an in vitro setting. The viability and cytotoxicity testing demonstrated no adverse effects of the hybrid system (Gel/Odex/TA/PCL-β-TCP) and significantly improved preosteoblast cell (MC3T3-E1) viability. Moreover, the addition of these microspheres indicated a favorable environment for cell growth and development. Furthermore, Gel/Odex/TA/6%PCL-β-TCP Ms and Gel/Odex/TA/4%PCL-β-TCP Ms hydrogels exhibited a significant increase in calcium deposition and alkaline phosphatase (ALP) activity, respectively. These results reinforce that this multifunctional composite hydrogel may serve as a promising scaffold for bone tissue regeneration.