A denture resin can contain residual monomer without releasing more methyl methacrylate than a negative control. And the 3D-printed material may look chemically different for reasons a single screening method cannot fully reveal. Methacrylic acid ester-based resins for denture fabrication release residual monomers and leachable substances that may interact with oral tissues.

With increasing adoption of CAD/CAM technologies, a systematic comparison of leachable substance profiles and surface characteristics across polymerization methods is needed. Concerns regarding the biocompatibility of methacrylic acid ester-based materials persist due to incomplete monomer conversion during polymerization.

Residual monomers and other leachable substances can diffuse into saliva and interact with cells of the oral mucosa in vivo, potentially triggering local inflammatory responses and systemic effects. Residual monomer content varies widely depending on the polymerization method, with heat-polymerized resins generally showing lower leachability than self-curing counterparts.

CAD/CAM milled dentures are presumed to exhibit greater mechanical and chemical stability due to industrial prepolymerization under controlled conditions, while three-dimensional printed resins may exhibit lower degrees of conversion and consequently higher leachability.

The study evaluated the chemical composition and leachable substance profile of two CAD/CAM-fabricated and two conventionally processed methacrylic acid ester-based denture materials. The hypothesis was that polymerization method and material formulation shape the chemical composition of the cured material and the spectrum of leachable substances.

Two CAD/CAM-fabricated and two conventionally processed denture base resins were included in the study, using cylindrical specimens ten millimeters in diameter. Prepolymerized resin specimens were milled from prefabricated resin blanks using a computer numerical control milling unit, while photopolymerized resin specimens were fabricated by stereolithography.

After printing, the photopolymerized specimens were washed in isopropanol for fifteen minutes, dried with compressed air, and post-polymerized in glycerol heated to eighty degrees Celsius with near-ultraviolet light for sixty minutes. The autopolymerized and thermally polymerized specimens were produced from the remaining rings of the prepolymerized blanks, injected at five bar pressure, and cured in a hot water bath.

The autopolymerized resin was cured at fifty-five degrees Celsius for thirty minutes, and the thermally polymerized resin at seventy to one hundred degrees Celsius for two hours. Surface roughness was measured on both the polished and unpolished, tissue-side surfaces at three locations per specimen per surface, using five specimens per material and twenty-times magnification by confocal microscopy.

Extracts from the four material groups used fourteen specimens pooled per group in a single extraction batch, following a surface-area-to-volume ratio of three square centimeters per milliliter. The extraction volume was zero point seven eight five milliliters per specimen, based on a total cylindrical surface area of two point three five six square centimeters.

Fourteen specimens were incubated in eleven milliliters of Keratinocyte Growth Medium 2 with supplements for forty-eight hours at thirty-seven degrees Celsius to simulate clinically relevant extraction conditions. Pure Keratinocyte Growth Medium 2 with supplements served as a negative control in all subsequently performed experiments.

A semi-quantitative gas chromatography–mass spectrometry screening examined the four solid specimens and their corresponding extracts. Analysis of the solid specimens revealed a total of twenty-four distinct compounds in the total ion chromatograms. Methyl methacrylate was detected in the prepolymerized, autopolymerized, and thermally polymerized specimens, but was not detected in the photopolymerized specimens, in line with their MMA-free, dimethacrylate-based formulation.

Thermal polymerization yielded the highest methyl methacrylate content in the solid material, followed by autopolymerized and prepolymerized specimens, while photopolymerized specimens contained no detectable methyl methacrylate. Although methyl methacrylate was detected in the solid material of the thermally polymerized, prepolymerized, and autopolymerized samples, concentrations in the corresponding extracts were at or below the negative control.

In panel A, the thermally polymerized trace forms a sharp peak near five minutes, reaching the top of the relative-intensity scale, while the other material traces remain much smaller or near baseline. In panel B, the extract traces cluster closely with the blue negative-control curve, showing only a modest shared bump just after five minutes rather than a distinct dominant peak.

The study examined how polymerization method and material formulation influence residual monomer content and leachable substance profiles in four methacrylate-based denture base resins. CAD/CAM-based fabrication encompasses subtractive manufacturing, in which an industrially prepolymerized resin blank is milled into the desired prosthetic shape, and additive manufacturing.

These approaches differ from conventional polymerization in their processing conditions, base monomer systems, and degree of conversion, with direct implications for the nature and quantity of leachable substances. GC–MS analysis of the solid specimens revealed that residual monomer content varied by polymerization method.

Among the MMA/PMMA-based materials, thermal polymerization yielded the highest MMA content, followed by autopolymerized and prepolymerized specimens. GC–MS detected a broader range of substances than those declared by the manufacturers.

This discrepancy underscores the importance of independent analytical characterization as a complement to manufacturer disclosure. Fabrication method and material formulation jointly determine the residual monomer content and extractable substance profile of the tested denture base resins, rather than polymerization method acting as an isolated variable.

Among the PMMA-based materials, residual monomer content was lowest for the CAD/CAM-milled specimens and highest for the thermally polymerized specimens, yet MMA released into the extraction medium remained negligible under the tested short-term conditions for all groups.

The three-dimensional printed resin showed a distinct set of detected constituents consistent with its formulation containing Bis-EMA, UDMA, and TMPTMA; because the screening may not reliably capture Bis-EMA and UDMA, their absence should not be interpreted as evidence that they are not leachable.

Surface roughness was comparable among materials on the polished surfaces but differed on the unpolished, tissue-contacting surfaces. Fabrication method and material formulation jointly shape what remains in denture resins and what can be extracted. The short-term extracts showed negligible MMA, but novel CAD/CAM materials still need material-specific, complementary toxicological evaluation.