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Limited studies have examined tissue formation via immunofluorescence in regenerative endodontic procedures (REPs) performed on infected human teeth. This report investigated the immunofluorescent histologic outcomes of REPs in which repeated canal disinfection was required.An 11-year-old girl presented with a fractured dens evaginatus (#29) with a sinus tract. Three visits involving chemical and mechanical disinfection were required before the resolution of clinical signs and symptoms was achieved and the REP could be performed. Healing of the periapical lesion was noted by 12 months, although the tooth remained unresponsive to sensibility tests. At 18 months, the tooth underwent orthodontic extraction. Histology and immunofluorescent techniques were used to stain for dentin sialophosphoprotein (DSPP), osteopontin (OPN), periostin, and myelin basic protein.Histology did not reveal a newly formed pulp-dentin complex. Neomineralized tissues were seen interlocked into preexisting dentinal tubules. Non–odontoblast-looking cells expressed different proportions of OPN and DSPP according to their location. Cells nearer to mineral trioxide aggregate expressed DSPP and OPN, but cells found apically expressed predominantly OPN. Myelin basic protein was found centrally within new tissues and did not extend to the coronal third. Periostin was highly expressed throughout the entire canal space, suggesting active repair processes instead of regeneration.This study shows the clinical effectiveness of REP in a tooth with recalcitrant infection with histologic demonstration of a reparative phenotype. De novo pulp regeneration in a clinical scenario may be limited by a complex interplay of host response factors.