It is not known to what extent residual infection may interfere with the success of pulp regeneration procedures. The aim of this study was to determine, radiographically and histologically, the effect of residual bacteria on the outcome of pulp regeneration mediated by a tissue-engineered construct as compared with traditional revascularization. Periapical lesions were induced in 24 canine teeth of 6 ferrets. After disinfection with 1.25% NaOCl and triple antibiotic paste, ferret dental pulp stem cells, encapsulated in a hydrogel scaffold, were injected into half the experimental teeth. The other half were treated with the traditional revascularization protocol with a blood clot scaffold. After 3 mo, block sections of the canine teeth were imaged radiographically and processed for histologic and histobacteriologic analyses. Associations between variables of interest were evaluated through mixed effects regression models. There were no significant differences between the 2 experimental groups in radiographic root development ( P > 0.05). There was a significant association between the presence of persistent periapical radiolucency and root wall thickness ( P = 0.02). There was also no significant difference in histologic findings between the 2 experimental groups ( P > 0.05). The presence of residual bacteria was significantly associated with lack of radiographic growth ( P < 0.001). The amount of dentin-associated mineralized tissue formed in teeth with residual bacteria was significantly less than in teeth with no residual bacteria ( P < 0.001). Residual bacteria have a critical negative effect on the outcome of regenerative endodontic procedures.

Calcium phosphate cements (CPCs) have excellent biocompatibility and osteoconductivity for dental, craniofacial, and orthopedic applications. This article reviews recent developments in stem cell delivery via CPC for bone regeneration. This includes: (1) biofunctionalization of the CPC scaffold, (2) co-culturing of osteoblasts/ endothelial cells and prevascularization of CPC, (3) seeding of CPC with different stem cell species, (4) human umbilical cord mesenchymal stem cell (hUCMSC) and bone marrow MSC (hBMSC) seeding on CPC for bone regeneration, and (5) human embryonic stem cell (hESC) and induced pluripotent stem cell (hiPSC) seeding with CPC for bone regeneration. Cells exhibited good attachment/proliferation in CPC scaffolds. Stem-cell-CPC constructs generated more new bone and blood vessels in vivo than did the CPC control without cells. hUCMSCs, hESC-MSCs, and hiPSC-MSCs in CPC generated new bone and blood vessels similar to those of hBMSCs; hence, they were viable cell sources for bone engineering. CPC with hESC-MSCs and hiPSC-MSCs generated new bone two-to three-fold that of the CPC control. Therefore, this article demonstrates that: (1) CPC scaffolds are suitable for delivering cells; (2) hUCMSCs, hESCs, and hiPSCs are promising alternatives to hBMSCs, which require invasive procedures to harvest with limited cell quantity; and (3) stem-cell-CPC constructs are highly promising for bone regeneration in dental, craniofacial, and orthopedic applications.KEY WOrDs: bone tissue engineering, dental and craniofacial, calcium phosphate scaffold, human embryonic stem cells, human induced pluripotent stem cells, animal studies.