Background: Periodontitis, which progressively destroys tooth-supporting structures, is one of the most widespread infectious diseases and the leading cause of tooth loss in adults. Evidence from preclinical trials and small-scale pilot clinical studies indicates that stem cells derived from periodontal ligament tissues are a promising therapy for the regeneration of lost/damaged periodontal tissue. This study assessed the safety and feasibility of using autologous periodontal ligament stem cells (PDLSCs) as an adjuvant to grafting materials in guided tissue regeneration (GTR) to treat periodontal intrabony defects. Our data provide primary clinical evidence for the efficacy of cell transplantation in regenerative dentistry. Methods: We conducted a single-center, randomized trial that used autologous PDLSCs in combination with bovine-derived bone mineral materials to treat periodontal intrabony defects. Enrolled patients were randomly assigned to either the Cell group (treatment with GTR and PDLSC sheets in combination with Bio-oss^®) or the Control group (treatment with GTR and Bio-oss^® without stem cells). During a 12-month follow-up study, we evaluated the frequency and extent of adverse events. For the assessment of treatment efficacy, the primary outcome was based on the magnitude of alveolar bone regeneration following the surgical procedure. Results: A total of 30 periodontitis patients aged 18 to 65 years (48 testing teeth with periodontal intrabony defects) who satisfied our inclusion and exclusion criteria were enrolled in the study and randomly assigned to the Cell group or the Control group. A total of 21 teeth were treated in the Control group and 20 teeth were treated in the Cell group. All patients received surgery and a clinical evaluation. No clinical safety problems that could be attributed to the investigational PDLSCs were identified. Each group showed a significant increase in the alveolar bone height (decrease in the bone-defect depth) over time (p < 0.001). However, no statistically significant differences were detected between the Cell group and the Control group (p > 0.05). Conclusions: This study demonstrates that using autologous PDLSCs to treat periodontal intrabony defects is safe and does not produce significant adverse effects. The efficacy of cell-based periodontal therapy requires further validation by multicenter, randomized controlled studies with an increased sample size. Trial Registration: NCT01357785 Date registered: 18 May 2011.

The management of periodontal tissue defects that result from periodontitis represents a medical and socioeconomic challenge. Concerted efforts have been and still are being made to accelerate and augment periodontal tissue and bone regeneration, including a range of regenerative surgical procedures, the development of a variety of grafting materials, and the use of recombinant growth factors. More recently, tissue-engineering strategies, including new cell- and/or matrix-based dimensions, are also being developed, analyzed, and employed for periodontal regenerative therapies. Tissue engineering in periodontology applies the principles of engineering and life sciences toward the development of biological techniques that can restore lost alveolar bone, periodontal ligament, and root cementum. It is based on an understanding of the role of periodontal formation and aims to grow new functional tissues rather than to build new replacements of periodontium. Although tissue engineering has merged to create more opportunities for predictable and optimal periodontal tissue regeneration, the technique and design for preclinical and clinical studies remain in their early stages. To date, the reconstruction of small- to moderate-sized periodontal bone defects using engineered cell–scaffold constructs is technically feasible, and some of the currently developed concepts may represent alternatives for certain ideal clinical scenarios. However, the predictable reconstruction of the normal structure and functionality of a tooth-supporting apparatus remains challenging. This review summarizes current regenerative procedures for periodontal healing and regeneration and explores their progress and difficulties in clinical practice, with particular emphasis placed upon current challenges and future possibilities associated with tissue-engineering strategies in periodontal regenerative medicine.