(T1230-07-41) Development of 3D-Printed Chitosan/P-Coumaric Acid Scaffolds for Wound Healing: Antibacterial Properties and Drug Release Kinetics

Purpose: This study aimed to develop a biocompatible scaffold using chitosan and p-coumaric acid (PCA) through 3D printing technology for patient-centered wound healing applications. The primary objective was to investigate the antibacterial properties of P-CA when incorporated into a chitosan-based scaffold, with a focus on evaluating potential synergistic effects.The combination of P-CA and chitosan may lead to a more robust and effective treatment for wounds, as they can complement each other's actions to promote healing and protect against damage. Additionally, the study aimed to assess the release kinetics of PCA from the printed scaffold.

Methods: Chitosan, polyethylene oxide (PEO), and polycaprolactone (PCL) were used in powder and pellet forms, respectively, with PCL pellets undergoing cryomilling for uniform particle distribution. The physical mixtures were extruded using a co-rotating twin-screw extruder at 110°C and 50 rpm through a 2.5 mm die. Scaffolds (20 × 20 × 1 mm) were 3D-printed with 80% infill using a Bowden FDM 3D printer. Thermal properties were analyzed via DSC and TGA, while FT-IR was used for chemical characterization. Surface roughness was assessed using optical profilometry. Scaffolds were incubated at 37°C and 200 rpm to study drug release, with absorbance measured at 310 nm to quantify p-coumaric acid (P-CA). Drug release kinetics were evaluated using Korsmeyer–Peppas, zero-order, first-order, and Higuchi models. The antibacterial activity was evaluated using the disk diffusion (zone inhibition) assay against Escherichia coli to assess the potential synergistic effect between p-coumaric acid (P-CA) and chitosan.

Results: The scaffold was successfully printed using Hot-Melt Extrusion (HME) after multiple trials, with an optimized formulation ratio of PCL/Chitosan/P-CA//PEO N80 at 35:20:10:35 (Fig. 1). Differential Scanning Calorimetry (DSC) analysis showed a significant reduction in the melting peak of P-CA (~210 °C), indicating a transition to the amorphous state (Fig. 2). The drug release study achieved a 3-day sustained release (Fig. 3), and kinetic modeling revealed that the scaffold followed the Korsmeyer-Peppas model (R² = 0.991). The release exponent (n > 1.0) suggests a super-case II transport mechanism, indicating that both drug diffusion and polymer relaxation contributed to the release process. Antibacterial results (Fig. 4) showed that PCL alone (Group I) exhibited no antibacterial activity, while PCL + Chitosan (Group II) demonstrated moderate inhibition. The strongest antibacterial effect was observed in Group III (PCL + Chitosan + P-CA), confirming the synergistic effect of P-CA and chitosan, while Group IV (P-CA alone) exhibited notable inhibition but was slightly less effective than Group III.

Conclusion: The optimized bio-natural scaffold was successfully fabricated using 3D printing technology, demonstrating high structural integrity, uniformity, and achieving a 3-day sustained drug release. Furthermore, the scaffold demonstrated significant antibacterial activity, indicating the effective synergistic action of the combination of protocatechuic acid (P-CA) and chitosan for enhanced wound healing applications.

Acknowledgements: The authors gratefully acknowledge the School of Engineering, Department of Mechanical Engineering at the University of Mississippi for providing access to the Digital Microscope VHX-5000 and for their support in generating the topography image.


Figure 1. 3 D printed scaffold and Surface topography of the scaffold.


Figure 2. Differential Scanning Calorimetry of the Scaffold components.


Figure 3. Antibacterial activity of the Scaffold.