This paper investigates the influence of cavity configuration and post-endodontic restoration on the fracture resistance, failure mode and stress distribution of premolars by using a method of fracture failure test and finite elements analysis (FEA) coupled to Weibull analysis (WA). One hundred premolars were divided into one control group (Gcontr) (n = 10) and three experimental groups, according to the post-endodontic restoration (n = 30), G1, restored using composite, G2, restored using single fiber post and G3, restored using multifilament fiberglass posts (m-FGP) without post-space preparation. Each experimental group was divided into three subgroups according to the type of coronal cavity configuration (n = 10): G1O, G2O, and G3O with occlusal (O) cavity configuration; G1MO, G2MO, and G3MO with mesio-occlusal (MO); and G1MOD, G2MOD, and G3MOD with mesio-occluso-distal (MOD). After thermomechanical aging, all the specimens were tested under compression load, and failure mode was determined. FEA and WA supplemented destructive tests. Data were statistically analyzed. Irrespective of residual tooth substance, G1 and G2 exhibited lower fracture resistance than Gcontr (p < 0.05), whereas G3 showed no difference compared to Gcontr (p > 0.05). Regarding the type of restoration, no difference was highlighted between G1O and G2O, G1MO and G2MO, or G1MOD and G2MOD (p > 0.05), whereas G3O, G3MO, and G3MOD exhibit higher fracture resistance (p < 0.05) than G1O and G2O, G1MO and G2MO, and G1MOD and G2MOD, respectively. Regarding cavity configuration: in G1 and G2, G1O and G2O exhibited higher fracture resistance than G1MOD and G2MOD, respectively (p < 0.05). In G3, there was no difference among G3O, G3MO and G3MOD (p > 0.05). No difference was found among the different groups and subgroups regarding the failure mode. After aging, premolars restored with multifilament fiberglass posts demonstrated fracture resistance values comparable to those of an intact tooth, irrespective of the different type of cavity configuration.
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