To synthesize and evaluate the available data on the biocompatibility of 3D-printed resins for temporary restorations in fixed prosthodontics, compared to conventional acrylic resins and CAD/CAM-milled resins.

Secondary objectives:

Identify the effect of post-processing parameters (post-curing, post-washing) on cytotoxicity. Compare the elution profiles of residual monomers according to manufacturing technology. Evaluate available in vivo clinical data (periodontal response, tissue inflammation). Identify methodological gaps and formulate recommendations for future research.

Population/Material (P): Polymer resins for fixed temporary prosthetic restorations (crowns and bridges). Included are in vitro studies on oral cell lines (gingival fibroblasts, keratinocytes), on organotypic models, as well as in vivo studies (animal models or human clinical trials).

Intervention (I): Specimens or restorations fabricated using 3D printing technologies (including digital light processing (DLP), stereolithography (SLA), liquid crystal display (LCD), or vat photopolymerization).

Comparison (C): Conventional resins (self-curing polymethyl methacrylate (PMMA), bis-acrylic resins) and/or polymers machined using subtractive technology (CAD/CAM).

Outcomes (O): The primary evaluation criteria include biological markers of cellular biocompatibility (cell viability rate (%), cytotoxicity) and chemical indicators of polymerization (degree of conversion (DC %), kinetics, and elution profiles of residual monomers in µg/mL). Secondary criteria include the inflammatory response (cytokines IL-6, IL-8), oxidative stress (ROS), and bacterial biofilm colonization.

Question: In the available in vitro and in vivo studies, do 3D-printed temporary resins exhibit a biocompatibility profile that is comparable to, inferior to, or superior to that of conventional resins (acrylic and bis-acrylic) and CAD/CAM-milled resins, and which post-processing parameters influence this profile?

A literature search was conducted in the following electronic databases to identify relevant studies: PubMed, Web of Science, OpenAlex, and Scopus.

Search equations were developed by combining MeSH terms and keywords, using Boolean operators (AND, OR) to maximize the sensitivity and specificity of the results.

Inclusion Criteria:

In vitro studies evaluating the cytotoxicity, biocompatibility, or monomer release of resins for fixed, tooth-supported temporary restorations. In vivo studies (animal or clinical) evaluating the tissue response to 3D-printed temporary resins. Studies comparing 3D-printed temporary resins using DLP, SLA, VAT, or PolyJet technologies to conventional or CAD/CAM resins. At least one quantitative biological outcome was reported (cell viability, monomer elution, degree of conversion). Publication between January 1, 2015, and May 30, 2026. Languages: English. Publication in a peer-reviewed journal with quantitative data.

Exclusion Criteria:

Permanent/definitive resins (excluding restorations intended to last ≥ 5 years). Resins for removable dentures, implant drilling guides, orthodontics (unless biological evaluation of monomers applies to temporary restorations), and occlusal splints. Studies without a comparison group: Absence of conventional or CAD/CAM-milled resin as a control.Letters to the editor, editorials, opinion pieces, narrative reviews. Studies focusing exclusively on mechanical properties without any biological parameters.

To evaluate biocompatibility, the following thresholds were applied in accordance with ISO 10993-5:2009:

Cell viability: ≥70% is considered non-cytotoxic; <70% is considered cytotoxic. Monomer elution: No standardized threshold exists; values are reported descriptively. Inflammatory response (IL-6, IL-8, PGE2): A statistically significant increase (p < 0.05) relative to the control is considered a sign of inflammatory reaction. Oxidative stress (GSH/GSSG): A significant decrease in GSH or increase in GSSG (p < 0.05) is considered a sign of oxidative stress. Biofilm: The absence or significantly reduced presence of red-complex bacteria (Socransky classification) is considered a favorable profile.

The overall assessment of biocompatibility took into account all of these parameters, without the assignment of a single quantitative score.

Study selection was conducted independently by two reviewers, with any disagreements resolved by consensus. All 13 included studies are full peer-reviewed journal articles; no abstract-only records, conference proceedings, or web-only reports were retained.

The study selection process was conducted in two phases and documented using a PRISMA flow diagram:

Phase 1: Screening: Search results from various databases were compiled and exported to the Zotero reference management software to check for duplicates.

Phase 2: Eligibility: Articles selected at the end of the first phase underwent a full-text review. The same two authors independently read each article to confirm that it met all PICO criteria. The reasons for excluding articles not selected for full-text review were recorded.

A standardized data extraction form was developed, pre-tested on five pilot studies, and then used by two independent reviewers. Disagreements were resolved by consensus or arbitration by a third reviewer. The extracted variables included: material characteristics (composition, 3D printing technology, post-polymerization, post-washing), biological model, biological tests (viability, monomer elution, cytokines, oxidative stress, biofilm), comparators, compliance with ISO standards, and limitations reported by the authors. Table 1 presents a summary of the extracted data.

Table 1. Summary of the characteristics and main findings of the included studies (n = 13).

Abbreviations: 3D, three-dimensional printing; AR, conventional/thermal acrylic resin; BA, bis-acrylic resin; BoP, bleeding on probing; CAD/CAM, computer-aided design/manufacturing; CFU, colony-forming units; DC, degree of conversion; DLP, digital light processing; ELISA, enzyme-linked immunosorbent assay; FDI, World Dental Federation criteria; GGT, gamma-glutamyl transferase; GSH/GSSG, reduced/oxidized glutathione; hGF, human gingival fibroblasts; HPLC, high-performance liquid chromatography; IPA, isopropyl alcohol; ISO, International Organization for Standardization; PDL-hTERT, hTERT-immortalized periodontal ligament cells; PMMA, polymethyl methacrylate; RCT, randomized clinical trial; SEM, scanning electron microscopy; SLA, stereolithography; SRB, sulforhodamine B; TEGDMA, triethylene glycol dimethacrylate; UDMA, urethane dimethacrylate; UHPLC-MS/MS, ultra-high-performance liquid chromatography-tandem mass spectrometry; VAS, visual analog scale; VPI, visible plaque index; XTT, tetrazolium salt viability assay; ZR, zirconia.

The risk of bias was assessed by two independent reviewers. For the 12 in vitro studies, the QUIN tool (12 criteria, score out of 24, thresholds: low ≥ 17, moderate 12 - 16, high < 12) was used. For the randomized clinical trial, the Cochrane RoB 2.0 tool was used. Disagreements were resolved by consensus or arbitration by a third reviewer.

Narrative synthesis: Organized by biological outcome (cytotoxicity, elution, degree of conversion), printing technology, and post-processing parameters.

Meta-analysis: Not performed due to significant clinical and methodological heterogeneity among the studies (variability in resins, post-polymerization protocols, cell models, and viability assays). A narrative synthesis was preferred (PRISMA 2020).

A total of 822 studies were identified through the literature search. After removing duplicates (n = 208) and studies deemed outside the scope of the review (n = 533) based on their titles and abstracts, 81 studies were reviewed in full text. In total, 13 studies were eligible for inclusion in the review (Figure 1Figure 1).

Study Characteristics

The main characteristics of the included studies are summarized in Table 1. Of the 13 included studies, 12 were in vitro studies and one was a randomized clinical trial. The publications span the years 2021 to 2026.

The most frequently evaluated 3D-printed resin was NextDent C&B MFH (n = 5), followed by Cosmos Temp (n = 3). Comparators included self-curing acrylic resins (n = 8), machined CAD/CAM blocks (n = 7), and bis-acrylic composites (n = 4).

Figure 1. PRISMA flowchart 2020.

Biocompatibility was evaluated in 10 studies (cell viability, inflammatory response, oxidative stress). Monomer elution was quantified in 6 studies. Surface properties and biofilm formation were examined in 5 studies. The sole clinical trial evaluated FDI criteria, periodontal indices, and patient satisfaction.

The synthesis of results is organized according to three principal modifiers identified as sources of heterogeneity between studies: 1) extraction conditions, 2) cell model, and 3) post-polymerization protocol.

3.2.1. Effect of Extraction Conditions

Studies using pure undiluted extracts (Wuersching et al., 2022) reported more severe cytotoxicity than those using diluted extracts or limited direct contact (Alamo et al., 2022; Folwaczny et al., 2023). Berghaus et al. (2023) showed that elution into water (simulating saliva) was undetectable, whereas it was quantifiable in ethanol (worst-case scenario). These methodological differences partly explain the disparities observed across studies.

3.2.2. Effect of the Cell Model

Primary gingival fibroblasts (Britto et al., 2022; Wuersching et al., 2022) showed variable sensitivity depending on the materials, while oral keratinocytes (NOK-Si) (Alamo et al., 2022; Pacheco et al., 2025) showed generally lower sensitivity. Periodontal ligament cells (PDL-hTERT) (Folwaczny et al., 2023) were particularly sensitive to direct contact with conventional resins.

3.2.3. Effect of the Post-Polymerization Protocol

Extending post-polymerization time improves the cytocompatibility of 3D-printed resins. Alamo et al. (2022) observed a reduction of >70% in cell viability with 1 min of post-polymerization, whereas 20 min yielded a level comparable to CAD/CAM-milled resins. Pacheco et al. (2025) confirmed that monomer leaching is inversely proportional to post-polymerization time.

3.2.4. Synthesis of Results by Outcome Cytotoxicity and Monomer Elution

The results show that biocompatibility depends on the type of printed resin: Britto et al. (2022) demonstrated that the Cosmos Temp printed resin exhibited a viability rate of 92.9%, which was higher than that of acrylic resin (71.9%) [16]; similarly, Parakaw et al. (2023) reported that NextDent C&B MFH was non-toxic to gingival fibroblasts [17]. Conversely, Wuersching et al. (2022) observed that several printable resins (VSC, ND, VST, TP, P) were severely toxic, with viability close to 0% for VarseoSmile Temp [18].

Alamo et al. (2022) [19] and Pacheco et al. (2025) [20] demonstrated that cytotoxicity and monomer leaching depended on post-polymerization time: 1 minute induced a >70% reduction in cellular metabolism and high leaching, whereas 15 - 20 minutes yielded a profile similar to that of CAD/CAM resins.

Berghaus et al. (2022, 2023) [21][22] detected BisGMA in the printed eluates, with maximum elution in ethanol and none in water. Mudhaffer et al. (2025) demonstrated that printed temporary resins exhibited higher elution (53 - 87 µmol/L) than printed final resins (50 - 51 µmol/L) and the milled Lava Ultimate block (7.6 µmol/L), with no effect of print orientation [23].

SurfacePropertiesandBiofilm Formation

Surface roughness and texture (influenced by the material and manufacturing technique) played an important role, with smoother surfaces (machined PMMA) exhibiting less biofilm.

Parakaw et al. (2023) [17] and Wuerchsing et al. (2026) [24] reported that all tested restorations were non-toxic and promoted good fibroblast adhesion, but differed in the amount of biofilm formed.

Wuerchsing et al. (2026) identified a moderate positive correlation between surface roughness and the number of viable bacteria [24].

Uehara et al. (2025) observed that 3D-printed resins exhibited greater biofilm formation than acrylic resin, but their microbiological profile was less pathogenic (absence of the red complex) [25].

3D-printed resins for temporary restorations demonstrate generally acceptable performance in terms of biocompatibility and leaching, provided an adequate post-polymerization protocol is followed (≥15 - 20 minutes). Certainty of evidence was not formally graded using GRADE in this review. However, the overall certainty is considered low to very low for all outcomes: cytotoxicity and monomer elution data derive from heterogeneous in vitro studies with moderate risk of bias; biofilm data are limited to three studies with variable protocols; and clinical evidence is based on a single RCT with short follow-up. These limitations should be considered when interpreting the conclusions.

Among the 12 in vitro studies, only one (Uehara et al., 2025) had a low risk of bias (score 17/24). The other 11 studies (92%) had a moderate risk of bias (scores 12 - 15/24). The most frequently unreported criteria were assessor blinding (missing in 11 studies), randomization (missing in 11 studies), and sample size calculation (missing or incomplete in 10 studies). The clinical trial by de Souza et al. [26] (2024) showed a low risk of bias across all five domains of the Cochrane RoB 2.0 tool. No studies were excluded based on quality.

Alamo et al. (2022) [19] and Pacheco et al. (2025) [20] demonstrated a clear inverse relationship between post-polymerization duration and monomer release. A 1-minute post-curing time was insufficient and resulted in severe cytotoxicity, whereas a duration of 15 to 20 minutes achieved a biocompatibility profile equivalent to that of milled resins.

However, the heterogeneity of protocols across studies is striking. Post-polymerization durations vary from 5 to 30 minutes depending on the manufacturer, and washing conditions (solvent, duration, method) are rarely standardized. Several studies do not report light intensity (mW/cm²) or the exact wavelength, which limits reproducibility and comparability between studies. As Alamo et al. (2022) [19], post-polymerization affects not only monomer release but also surface properties. Prolonged post-polymerization can increase roughness or alter surface chemistry, thereby influencing bacterial adhesion.

Monomer elution: A key material-dependent mechanism. Mudhaffer et al. (2025) quantified the total elution of six 3D-printed resins [23]. The printed temporary resins (NextDent C&B MFH, Dima C&B temp, GC temp print) released more monomers (53 - 87 µmol/L) than the printed permanent resins (VarseoSmile Crownplus, Crowntec: 47 - 51 µmol/L) and than the milled Lava Ultimate block (7.6 µmol/L). This difference can be explained by the chemical composition: temporary resins contain monomers with lower molecular weights (UDMA, TEGDMA) that are more mobile and more easily leachable, whereas permanent resins incorporate more mineral fillers, reducing the extractable organic fraction.

Berghaus et al. (2023) demonstrated that the 50% filled 3D-printed composite exhibited a degree of conversion of 95.2%, comparable to milled blocks (94.3%) and higher than self-curing resins (89.1%) [22]. Importantly, no correlation was found between the degree of conversion and monomer elution, suggesting that other factors, such as polymer chain mobility, microporosity, and hydrophilicity, are key determinants in the release of residual monomers.

Berghaus et al. (2022) supplemented these findings by demonstrating that the 3D-printed composite behaved similarly to the machined material in response to enzymatic and hydrolytic degradation, whereas the self-curing material exhibited greater elution of Bis-GMA and TEGDMA [21]. All concentrations of eluted monomers remain below the EC50 values reported in the literature. However, as Mudhaffer et al. (2025) point out, in vitro conditions (extraction in a fixed volume, without renewal) do not replicate continuous salivary flow or chronic low-dose exposure, the genotoxic or sensitizing effects of which have not been evaluated [23].

Biofilm: Quantity vs. pathogenicity. The surface properties of 3D-printed resins differ from those of machined and conventional resins, with implications for biofilm formation. Parakaw et al. (2023) demonstrated that milled PMMA (VIPI block) exhibited the thinnest biofilm (7.5 µm), compared to 13.2 µm for NextDent C&B MFH and 23.1 µm for the self-curing Unifast Trad [17]. This result is consistent with the lower surface roughness of milled blocks, achieved through an industrial process involving high pressure and temperature.

Uehara et al. (2025) provided a more nuanced perspective: while 3D-printed resins (Cosmos Temp, Prizma 3D Bio Crown, Prizma 3D Bio Prov) did form a more abundant biofilm than conventional acrylic resin, this biofilm was less pathogenic, with an absence of bacteria from the red complex (P. gingivalis, T. forsythia, T. denticola). This result suggests that the surface chemistry of 3D-printed resins selects for a less virulent microbiota, potentially less harmful to periodontal tissues [25].

Wuersching et al. (2026) partially confirmed this result, showing that there was no significant difference in biofilm mass or CFU between 3D-printed, milled, and conventional resins. They identified a strong negative correlation between total interfacial tension and biofilm mass, and a moderate positive correlation between roughness (Ra) and the number of viable bacteria. Surface physicochemical properties (free energy, hydrophobicity, roughness) are therefore major determinants of bacterial colonization [24].

Clinical data: Only one randomized clinical trial was included (de Souza et al., 2024). This trial compared 42 temporary crowns (21 3D-printed, 21 conventional) on anterior implants. The results showed a shorter operative time for 3D printing (5 vs. 19 minutes, p < 0.001), but a higher rate of catastrophic fractures (19% vs. 0%, p = 0.05) and lower clinical success (76.2% vs. 100%). Patient satisfaction (aesthetics, phonetics, mastication, comfort) and periodontal indices (VPI, BoP) were similar between the two groups. These results indicate that, from a biological and aesthetic standpoint, 3D-printed crowns are equivalent to conventional crowns, but their mechanical durability is inferior. No other clinical studies were identified, which constitutes a major gap in the literature [26].

This review has several limitations: The majority of studies are in vitro and do not replicate oral complexity (salivary flow, acquired pellicle, mature biofilm); heterogeneity of post-polymerization protocols prevents any robust meta-analysis; lack of long-term clinical data (>1 year); risk of publication bias (underrepresentation of negative results). Finally, in vitro studies use pure extracts or direct contact conditions that do not reflect in vivo saliva dilution and turnover.

For research: Future studies must accurately report post-polymerization parameters (duration, temperature, mW/cm², wavelength, washing solvent), comply with ISO 10993-5 and -12 standards, and include machined and conventional controls. Randomized clinical trials with a follow-up period of ≥1 year are urgently needed to evaluate not only biocompatibility but also mechanical durability.

For clinical practice: The biocompatibility of printed resins depends strictly on adherence to the manufacturer’s protocols, with post-curing of ≥15 - 20 minutes (Alamo et al., 2022 [19]; Pacheco et al., 2025) [20] and adequate rinsing. The use of 3D-printed resins for long-term restorations (>6 months) or for multi-unit bridges is currently not supported by clinical evidence: the sole included trial (de Souza et al., 2024) [26] reported a fracture rate of 19% vs. 0% for conventional resins, and no other clinical studies are available. Further randomized trials with longer follow-up are needed before these indications can be recommended. For single-unit restorations, they may be an acceptable alternative to conventional resins, provided the patient is informed and closely monitored. The choice of a 3D-printed resin should be guided by validated biocompatibility data for that specific product, not by a generic trust in the technology.