Hybrid-Reinforced Phytocannabinoid-Functionalized PMMA Denture Base Composites: An In Vitro Study

Polymethyl methacrylate (PMMA) remains the material of choice for denture base fabrication; however, its limited mechanical durability and susceptibility to microbial colonization continue to compromise long-term clinical performance. This study aimed to engineer a multifunctional PMMA denture base composite through hybrid reinforcement with hemp fiber (HF), silk fibroin (SF), and phytocannabinoid-rich fractions (Frac1–Frac4) and to comprehensively evaluate its mechanical, structural, antimicrobial, and cytocompatibility properties. Twenty experimental groups were fabricated, including conventional PMMA, PMMA/HF, PMMA/SF, and hybrid PMMA/HF/SF systems with or without 1 wt% phytocannabinoid fractions. Flexural strength, elastic modulus, Charpy impact strength, and Vickers hardness were determined according to standardized protocols. Structural characterization was performed using ATR-FTIR, X-ray diffraction (XRD), and scanning electron microscopy (SEM). Bacterial metabolic viability of Streptococcus mutans and Lactobacillus acidophilus was evaluated using the MTT assay, while cytotoxicity was assessed using the LDH assay. Mechanical outcomes were analyzed using two-way factorial ANOVA to evaluate the main effects of the material system and phytocannabinoid condition and their interaction; significant interactions were followed by Tukey-adjusted simple-effects comparisons. Biological data were analyzed using the procedures specified for those outcomes (α = 0.05). The material system and phytocannabinoid condition significantly affected all mechanical properties (all main-effect p-values ≤ 6.068 × 10−83). Significant material system × phytocannabinoid condition interactions were observed for flexural strength, Vickers hardness, and impact strength, whereas the interaction was not significant for elastic modulus. The PMMA/HF/SF control group exhibited the highest flexural strength (138.04 ± 2.05 MPa), elastic modulus (2.519 ± 0.017 GPa), Vickers hardness (26.14 ± 0.22 VHN), and impact strength (24.22 ± 0.22 kJ/m2). Although phytocannabinoid incorporation produced a gradual reduction in mechanical performance, all hybrid-reinforced formulations remained mechanically superior to unmodified PMMA. ATR-FTIR and XRD analyses confirmed preservation of the characteristic PMMA chemical structure and amorphous polymer architecture without evidence of new crystalline phases. SEM demonstrated markedly reduced bacterial adhesion and biofilm formation on phytocannabinoid-containing composites. The PMMA/HF/SF formulations exhibited the greatest antibacterial performance, reducing bacterial viability to 14.59–19.40% for L. acidophilus and 15.21–24.13% for S. mutans, while maintaining low cytotoxicity (<5%). These findings demonstrate the feasibility of combining hybrid natural-fiber reinforcement with phytocannabinoid functionalization in PMMA and support further investigation of this approach for denture base applications.