Introduction: Resorbable synthetic scaffolds are promising for different indications, especially in the context of bone regeneration. However, they require additional biological components to enhance their osteogenic potential. In addition to different cell types, autologous blood-derived matrices offer many advantages to enhance the regenerative capacity of biomaterials. The present study aimed to analyze whether biologization of a PCL-mesh coated using differently centrifuged Platelet rich fibrin (PRF) matrices will have a positive influence on primary human osteoblasts activity in vitro. A polymeric resorbable scaffold (Osteomesh, OsteoporeTM (OP), Singapore) was combined with differently centrifuged PRF matrices to evaluate the additional influence of this biologization concept on bone regeneration in vitro. Peripheral blood of three healthy donors was used to gain PRF matrices centrifuged either at High (710× g, 8 min) or Low (44× g, 8 min) relative centrifugal force (RCF) according to the low speed centrifugation concept (LSCC). OP-PRF constructs were cultured with pOBs. POBs cultured on the uncoated OP served as a control. After three and seven days of cultivation, cell culture supernatants were collected to analyze the pOBs activity by determining the concentrations of VEGF, TGF-β1, PDGF, OPG, IL-8, and ALP- activity. Immunofluorescence staining was used to evaluate the Osteopontin expression of pOBs. After three days, the group of OP+PRFLow+pOBs showed significantly higher expression of IL-8, TGF-ß1, PDGF, and VEGF compared to the group of OP+PRFHigh+pOBs and OP+pOBs. Similar results were observed on day 7. Moreover, OP+PRFLow+pOBs exhibited significantly higher activity of ALP compared to OP+PRFHigh+pOBs and OP+pOBs. Immunofluorescence staining showed a higher number of pOBs adherent to OP+PRFLow+pOBs compared to the groups OP+PRFHigh+pOBs and OP+pOBs. To the best of our knowledge, this study is the first to investigate the osteoblasts activity when cultured on a PRF-coated PCL-mesh in vitro. The presented results suggest that PRFLow centrifuged according to LSCC exhibits autologous blood cells and growth factors, seem to have a significant effect on osteogenesis. Thereby, the combination of OP with PRFLow showed promising results to support bone regeneration. Further in vivo studies are required to verify the results and carry out potential results for clinical translation.
Alveolar ridge augmentation is an important dental procedure to increase the volume of bone tissue in the alveolar ridge before the installation of a dental implant. To meet the high demand for bone grafts for alveolar ridge augmentation and to overcome the limitations of autogenous bone, allografts, and xenografts, researchers are developing bone grafts from synthetic materials using novel fabrication techniques such as 3D printing. To improve the clinical performance of synthetic bone grafts, stem cells with osteogenic differentiation capability can be loaded into the grafts. In this pilot study, we propose a novel bone graft which combines a 3D-printed polycaprolactone–tricalcium phosphate (PCL-TCP) scaffold with adipose-derived mesenchymal stem cells (AD-MSCs) that can be harvested, processed and implanted within the alveolar ridge augmentation surgery. We evaluated the novel bone graft in a porcine lateral alveolar defect model. Radiographic analysis revealed that the addition of AD-MSCs to the PCL-TCP scaffold improved the bone volume in the defect from 18.6% to 28.7% after 3 months of healing. Histological analysis showed the presence of AD-MSCs in the PCL-TCP scaffold led to better formation of new bone and less likelihood of fibrous encapsulation of the scaffold. Our pilot study demonstrated that the loading of AD-MSCs improved the bone regeneration capability of PCL-TCP scaffolds, and our novel bone graft is suitable for alveolar ridge augmentation.
Tooth loss greatly affects a person's quality of life and many turn to dental implants to replace lost teeth. The success of a dental implant depends on the amount of alveolar bone supporting the implant, and thus, bone augmentation is often necessary to preserve or build up bone volume in the alveolar ridge. Bone can be augmented with autogenous bone, allografts, or xenografts, but the limitations of such natural bone grafts prompt researchers to develop synthetic scaffolds supplemented with cells and/or bioactive agents as alternative bone grafts. The translation of these combination scaffolds from the laboratory to the clinic requires reliable experimental models that can simulate the clinical conditions in human patients. In this article, we describe the use of a porcine alveolar defect model as a platform to evaluate the efficacy of a novel combination of a three-dimensional-printed polycaprolactone-tricalcium phosphate (PCL-TCP) scaffold and adipose-derived mesenchymal stem cells (AD-MSCs) in lateral alveolar augmentation. The surgical protocol for the defect creation and regenerative surgery, as well as analytical methods to determine the extent of tissue regeneration, are described and discussed.