Cell-Based Therapies for Alveolar Bone and Periodontal Regeneration: Concise Review

Abstract

Current regenerative strategies for alveolar bone and periodontal tissues are effective and well adopted. These are mainly based on the use of a combination of synthetic/natural scaffolds and bioactive agents, obviating the incorporation of cells. However, there are some inherent limitations associated with traditional techniques, and we hypothesized that the use of cell-based therapies as part of comprehensive regenerative protocols may help overcome these hurdles to enhance clinical outcomes. We conducted a systematic review of human controlled clinical trials investigating the clinical and/or histological effect of the use of cellbased therapies for alveolar bone and periodontal regeneration and explored the translational potential of the different cell-based strategies identified in the included trials. A total of 16 studies (11 randomized controlled trials, 5 controlled clinical trials) were included for data synthesis and qualitative analysis with meta-analyses performed when appropriate. The results suggest a clinical benefit from the use of cell therapy. Improved outcomes were shown for alveolar ridge preservation, lateral ridge augmentation, and periodontal regeneration. However, there was insufficient evidence to identify best-performing treatment modalities amongst the different cell-based techniques. In light of the clinical and histological outcomes, we identify extraction socket and challenging lateral and vertical bone defects requiring bone block grafts as strong candidates for the adjuvant application of mesenchymal stem cells. Given the complexity, invasiveness, and costs associated with techniques that include "substantial manipulation" of tissues and cells, their additional clinical benefit when compared with "minimal manipulation" must be elucidated in future trials. STEM CELLS Cell-based therapies have the potential to improve outcomes of regenerative treatment in the oral cavity. Extraction sockets and challenging lateral/vertical bone defects requiring bone block grafts are ideal candidates for the adjuvant application of mesenchymal stem cells. The present review showed that there is insufficient evidence to identify best-performing treatment modalities among the different cell-based techniques. Given the complexity, invasiveness, and costs associated with the "substantial manipulation" of tissues and cells, the clinical benefit of these techniques when compared with "minimal manipulation" must be elucidated. Further research evaluating the effectiveness of simple, fast, and economical methods for cell harvesting and processing is warranted.

Low‐intensity pulsed ultrasound promotes the formation of periodontal ligament stem cell sheets and ectopic periodontal tissue regeneration

“…Several studies have demonstrated that transplantation of in vitro ‐amplified PDLSCs and scaffolds into the defect could potently improve the repair of periodontal tissue structures in animal models 11‐13 . However, traditional tissue engineering often uses trypsin digestion to obtain individual cells, which not only loses the extracellular matrix (ECM) components but also destroys the biological connection between cells and reduces cell utilization efficiency 14,15 . In order to solve these limitations, Okano and coworkers developed cell‐sheets technology 16 .…”

Clinical Application of Bone Marrow Mesenchymal Stem/Stromal Cells to Repair Skeletal Tissue

“…While this strategy has not yet been implemented in the clinic, several clinical studies have been conducted utilizing exogenous stem cells although few have investigated BMSC stem cell based treatment options. Rather dental derived cell options have been employed for dental, periodontal, gingival and bone regeneration clinical trials, including dental pulp, gingival and periodontal ligament derived stem/progenitor cells [ 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 ].…”

“…There are limited clinically available therapeutic treatments for periodontitis apart from mechanical or surgical debridement with grafting procedures. Therefore stem cell based approaches have been explored to improve functional regeneration of lost bone [ 182 ]. In a phase I/II clinical trial based on preclinical studies, autologous BMSC combined with platelet-rich plasma, and a biodegradable 3D woven-fabric composite scaffold showed efficacy, stability and safety for periodontists over a 36 month period [ 54 ].…”

A tissue‐engineered biocomplex for periodontal reconstruction. A proof‐of‐principle randomized clinical study

“…In quest of a treatment approach with a consistent and clinical worthwhile benefit, tissue engineering (TE), based on the triad of mesenchymal stem cells (MSCs), biomolecules and scaffolds have been considered as an alternative for periodontal regeneration (Hynes et al, 2012). Mesenchymal stem cells can be expanded ex vivo to several millions of cells from a small tissue biopsy (Bakopoulou et al, 2017), or they can be minimally manipulated in the form of micro‐grafts (Trovato et al, 2015), having practical values as culture expanding procedures are avoided (Moreno Sancho et al, 2019). Successful MSC‐based therapies necessitate the selection of the most suitable cell source for the intended clinical application (Egusa et al, 2012), and autologous alveolar bone marrow MSCs (a‐BMMSCs) were elected for current use (Mason et al, 2014; Brennan et al, 2017; Cao et al, 2020).…”