Stem Cell-Based Tissue Engineering for Cleft Defects: Systematic Review and Meta-Analysis

Objectives This study aimed to analyze the efficacy of stem cell-based tissue engineering for the treatment of alveolar cleft (AC) and cleft palate (CP) defects in animal models. Design Systematic review and meta-analysis. Setting Preclinical studies on alveolar cleft repair in maxillofacial practice. Patients, Participants Electronic search was performed using PubMed, Embase, and Cochrane databases. Pre-clinical studies, where stem cell-based tissue engineering was used in the reconstruction of AC and CP in animal models were included. Quality of the selected articles was evaluated using SYRCLE (SYstematic Review Centre for Laboratory animal Experimentation). Interventions Review of alveolar cleft bone augmentation interventions in preclinical models. Main Outcome Measures Outcome parameters registered were new bone formation (NBF) and/or bone mineral density (BMD). Results Thirteen large and twelve small animal studies on AC (21) and CP (4) reconstructions were included. Studies had an unclear-to-high risk of bias. Bone marrow mesenchymal stem cells were the most widely used cell source. Meta-analyses for AC indicated non-significant benefits in favor of: (1) scaffold + cells over scaffold-only (NBF P = .13); and (2) scaffold + cells over empty control (NBF P = .66; BMD P = .31). Interestingly, dog studies using regenerative grafts showed similar to superior bone formation compared to autografts. Meta analysis for the CP group was not possible. Conclusions AC and CP reconstructions are enhanced by addition of osteogenic cells to biomaterials. Directions and estimates of treatment effect are useful to predict therapeutic efficacy and guide future clinical trials of bone tissue engineering.