Hydrogels as Carriers for Periodontal Ligament Stem Cells in Bone Repair: A Systematic Review

Hydrogels have emerged as promising delivery vehicles for periodontal ligament stem cells (PDLSCs) due to their biocompatibility and resemblance to the native extracellular matrix. The objective of this systematic review was to evaluate the efficacy of hydrogels as delivery vehicles for PDLSCs in animal models of bone regeneration. This systematic review is reported according to the (Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and included only in vivo studies evaluating PDLSCs encapsulated in hydrogels for the regeneration of periodontal, alveolar, mandibular, calvarial, or orthodontic defects. Searches were conducted in PubMed, Scopus, Embase, and Web of Science until March 2025. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation tool. Eleven studies were included. Hydrogels included gelatin methacrylate, alginate, chitosan-based matrices, collagen, and thermosensitive poly (lactic-co-glycolic acid)-polyethylene glycol-poly (lactic-co-glycolic acid), functionalized or not with growth factors, bioactive peptides, or nanoparticles. Quantitative microcomputed tomography (micro-CT) analyses assessed bone volume/total volume, bone mineral density, and trabecular thickness. Osteogenic induction typically involved the use of dexamethasone, β-glycerophosphate, and ascorbic acid. Histology confirmed new bone formation and, occasionally, vascularization. In periodontal defects, five studies showed enhanced bone fill and periodontal ligament-like tissue formation. Alveolar bone models reported improved mineralization and neovascularization in two studies. Mandibular defects, evaluated in large animals, exhibited trabecular bone formation. One calvarial and one orthodontic bone loss model reported increased bone density and accelerated deposition, respectively. Due to substantial methodological heterogeneity, a qualitative synthesis was performed. The risk of bias was generally high or unclear in the blinding and allocation domains. The main limitations of this review included heterogeneity across animal models, hydrogel formulations, and outcome measures. Hydrogel-encapsulated PDLSCs promote bone regeneration across diverse defect types, particularly when delivered via injectable and functionalized scaffolds in animal models.