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

Abstract

Aim: To assess the safety/efficacy of a tissue-engineered biocomplex in periodontal reconstruction.Methods: Twenty-seven intrabony defects were block-randomized across three treatment groups: Group-A (N A = 9) received autologous clinical-grade alveolar bone marrow mesenchymal stem cells (a-BMMSCs), seeded into collagen scaffolds, enriched with autologous fibrin/platelet lysate (aFPL). In Group-B (N B = 10), the collagen scaffold/aFPL devoid of a-BMMSCs filled the osseous defect. Group-C (N C = 8) received Minimal Access Flap surgery retaining the soft tissue wall of defects identically with Groups-A/-B. Subjects were clinically/radiographically assessed before anaesthesia (baseline) and repeatedly over 12 months.Results: Quality controls were satisfied before biocomplex transplantation. There were no adverse healing events. All approaches led to significant clinical improvements (p < .001) with no inter-group differences. At 12 months, the estimated marginal means for all groups were as follows: 3.0 (95% CI: 1.9-4.1) mm for attachment gain; 3.7 (2.7-4.8) mm for probing pocket depth reduction; 0.7 (0.2-1.3) mm increase in recession. An overall greater mean reduction in the radiographic Cemento-Enamel Junction to Bottom Defect (CEJ-BD) distance was found for Groups-A/-C over Group-B (p < .023). Conclusion:Radiographic evidence of bone fill was less pronounced in Group-B, although clinical improvements were similar across groups. All approaches aimed to trigger the innate healing potential of tissues. Cell-based therapy is justified for periodontal reconstruction and remains promising in selected cases.

Stem Cell Transplantation and Cell-Free Treatment for Periodontal Regeneration

“…Recently, clinical studies on periodontal tissue regeneration by stem cell transplantation in humans have been reported. In three of these studies, there was a trend toward improvement of clinical parameters in the stem cell transplantation group; however, no statistically significant differences were observed [60,62,63]. Autologous cells were used in these studies, and the results of the studies differed from the results of previous animal studies.…”

“…Human clinical studies have already begun based on these animal studies. The results of the controlled clinical trial in human patients are summarized in Table 2 [59][60][61][62][63]. All of these studies confirmed the safety of stem cell transplantation and reported that clinical parameters such as pocket depth, clinical attachment level, and radiographic bone volume tended to improve by stem cell transplantation [59][60][61][62][63].…”

“…The results of the controlled clinical trial in human patients are summarized in Table 2 [59][60][61][62][63]. All of these studies confirmed the safety of stem cell transplantation and reported that clinical parameters such as pocket depth, clinical attachment level, and radiographic bone volume tended to improve by stem cell transplantation [59][60][61][62][63]. However, of the five meta-analyses, two found statistically significant differences between control and cell treatment.…”

“…The safety of stem cell transplantation for periodontal regeneration has been reported by many clinical studies [59][60][61][62][63]72]. Safety considerations regarding autologous stem cell transplantation include the transmission of infection during ex vivo expansion, and tumor or unintended tissue formation after transplantation.…”

Microbial–stem cell interactions in periodontal disease

“…Culture-expanded MSCs have been successfully used in regenerative medicine in combination with biomaterials for the regeneration of oral and maxillofacial bone deficiencies [45][46][47][48]. Despite these promising clinical results, the use of autologous MSCs has some major limitations such as regulatory constraints, costs for amplification and quality controls, logistics of transportation, and surgical appliance of fresh cells and patient-to-patient variability in the cell expansion efficiency and regenerative outcome [49][50][51].…”