Preclinical Evidence for the Use of Oral Mesenchymal Stem Cell-Derived Extracellular Vesicles in Bone Regenerative Therapy: A Systematic Review.

The development of extracellular vesicles (EVs) therapies has revolutionized personalized medicine, opening up new possibilities for treatment. EVs have emerged as a promising therapeutic tool within this field due to their crucial role in intercellular communication across various cell types and organisms. This systematic review aims to evaluate the therapeutic potential of oral mesenchymal stem cell (MSC)-derived EVs for bone regeneration, specifically focusing on findings from preclinical models. Sixteen articles meeting the inclusion criteria were selected following document analysis. The biological effects of oral MSC-derived EVs predominantly involve the upregulation of proteins associated with angiogenesis, and inflammation resolution, alongside the downregulation of proinflammatory cytokines. Moreover, these therapeutic agents have been found to contain a significant quantity of different molecules (proteins, lipids, DNA, microRNAs, etc) further contributing to their modulatory potential. The findings from this systematic review underscore that oral MSC-derived EVs, irrespective of their specific population, have the ability to enhance the osteogenic repair response in maxillary bone or periodontal defects. In summary, this systematic review highlights the promising potential of oral MSC-derived EVs for bone regeneration based on evidence from preclinical models. The comprehensive assessment of their biological effects and the presence of microRNAs underscores their therapeutic significance. These findings support the utilization of oral MSC-derived EVs in enhancing the osteogenic repair response in various maxillary bone or periodontal defects, providing insights into the mechanisms involved and potential therapeutic applications in the field of personalized medicine.

Physico-chemical and biological characterization of a new bovine bone mineral matrix available for human usage.

BACKGROUND: Anorganic bovine bone has been deeply studied for bone regeneration in the oral cavity. Different manufacturing processes can modify the final composition of the biomaterial and the responses that induce. AIM: To evaluate the physico-chemical characteristics of a bovine bone mineral matrix and the clinical, radiographical, histological, and mRNA results after using it for maxillary sinus floor augmentation in humans. MATERIALS AND METHODS: First, the physical-chemical characteristics of the biomaterial were evaluated by X-ray powder diffraction, X-ray fluorescence, and electron microscopy. A frequently used biomaterial with the same animal origin was used as comparator. Then, a clinical study was designed for evaluating clinical, radiographical, histological, and mRNA outcomes. Patients in need of two-stage maxillary sinus floor augmentation were included in the study. Six months after the grafting procedure, a bone biopsy was collected for evaluation. RESULTS: In terms of physico-chemical characteristics, no differences were found between both biomaterials. Clinically, 10 patients were included in the study. After 6 months, clinical and radiographical data showed adequate outcomes for allowing implant placement. Histological, immunohistochemical and mRNA analyses showed that the biomaterial in use provides biological support to induce responses similar to those of other commonly used biomaterials. CONCLUSION: Bovine bone mineral matrix (Creos™ Xenogain) used as a single material for maxillary sinus floor augmentation shows adequate biological, clinical, and radiological outcomes. In fact, the results from this study are similar to those reported in the literature for another bovine bone-derived biomaterial with whom it shares composition and micro- and nanoscale characteristics.

Anorganic Bovine Bone Plus Recombinant Human Platelet-Derived Growth Factor-BB in Ridge Preservation: A Pilot Study.

PURPOSE: To determine clinical parameters, histologic features, and radiographic linear bone width changes of regenerated bone using different biomaterials for ridge preservation following tooth extraction. MATERIALS AND METHODS: For this pilot study, five patients were grafted with anorganic bovine bone and collagen plus recombinant human platelet-derived growth factor-BB (rhPDGF-BB), five patients were grafted with anorganic bovine bone and collagen alone, and five patients did not receive any biomaterial (control) after tooth extraction. Clinical, histologic, and radiographic evaluations were carried out 4 months postextraction. RESULTS: Differences in terms of buccolingual width were found when comparing the control group to the group grafted with anorganic bovine bone and collagen plus rhPDGF-BB (P = .012). No statistical differences were observed between the groups in terms of mineralized or nonmineralized tissue formation or in terms of the number of osteoblasts or osteocytes per mm2 after 4 months of healing. Interestingly, the number of vessels in the grafted area was found to be significantly different among the three groups (P = .005). The number of Musashi-1 positive cells was also different among groups, both in the mineralized and the nonmineralized areas of the grafted bone (P = .024 and .005, respectively). CONCLUSION: Anorganic bovine bone with bovine collagen is an efficient biomaterial to avoid postextraction resorption of the alveolar ridge. The addition of rhPDGF-BB appears to improve the biologic features of the newly formed bone and decrease bone resorption; further studies are needed for confirmation.

Personalized Bone Regeneration with a Novel Zirconia Membrane: A Case Report.

Varying amounts of bone resorption can occur following tooth loss, and this can lead to implant placement problems due to a lack of an alveolar ridge with suitable osseous dimensions. There are many techniques for bone regeneration and many types of barriers, including polytetrafluoroethylene, collagen, and titanium meshes. The present case report describes the use of a customized CAD/CAM zirconia barrier for vertical ridge augmentation. A bone height gain of 12 mm was observed, as well as 8 mm of width. Subsequent histologic analysis revealed an excellent bone quality, allowing successful implant placement.

Biphasic hydroxyapatite and ß-tricalcium phosphate biomaterial behavior in a case series of maxillary sinus augmentation in humans.

OBJECTIVES: The aim of this study was to evaluate and compare the morphometric components and the histological properties of pristine bone and bone grafted with a biphasic ß-tricalcium phosphate in humans using the maxillary sinus model. Reparative mesenchymal stem cells in the pristine bone and graft were also evaluated. MATERIALS AND METHODS: For this prospective case series, sinus augmentation was performed using a biphasic ß-tricalcium phosphate. After 6 months of healing, a core of remnant native alveolar bone and grafted bone was collected with a trephine. Histological, histomorphometrical, and immunohistochemical techniques were performed. Radiological analysis through cone beam computerized tomography was also conducted. RESULTS: A total of 10 patients were enrolled in this study. Radiologically, patients showed an average increase of crestal bone of 8.03 ± 1.72 mm. Morphologically, the grafted area was composed by 34.93 ± 14.68% of new mineralized tissue, 9.82 ± 11.42% of remnant biomaterial particles, and 55.23 ± 11.03% non-mineralized tissue. Histologically, we found no differences in the number of osteocytes per mm2 (p = 0.674), osteoblasts (p = 0.893), and blood vessels (p = 0.894) in the grafted area compared to the pristine bone. Differences were found on the number of osteoclasts (15.57 ± 27.50 vs. 5.37 ± 16.12, p = 0.027). The number of Musashi-1 positive mesenchymal cells (239.61 ± 177.4 vs. 42.11 ± 52.82, p = 0.027) was also significantly higher in the grafted area than in the pristine bone. CONCLUSION: Biphasic ß-tricalcium phosphate is a suitable biomaterial to be used in the formation of new bone in sinus floor elevation procedures in humans, not only from the histomorphometrical point of view, but also regarding the cellular and vascular quality of the regenerated bone.

Composite Alloplastic Biomaterial vs. Autologous Platelet-Rich Fibrin in Ridge Preservation.

AIM: The aim of this study was to examine the clinical and histological differences of using a combination of alloplastic beta triphasic calcium phosphate (ß-TCP) and a cross-linked collagen membrane versus autologous platelet-rich fibrin (PRF-L) in ridge preservation after dental extraction. MATERIAL AND METHODS: Fifty-one patients were included in this observational case-series study. Dental extractions were performed, after which 25 patients were grafted with ß-TCP and 26 with PRF-L. After four months of healing, clinical, radiological, histomorphometric and histological evaluations were performed. RESULTS: A significantly higher percentage of mineralized tissue was observed in samples from the PRF-L grafted areas. Cellularity was higher in PRF-L grafted areas (osteocytes in newly formed bone per mm² = 123.25 (5.12) vs. 84.02 (26.53) for PRF-L and ß-TCP, respectively, p = 0.01). However, sockets grafted with PRF-L showed a higher reduction in the bucco-lingual dimension after four months of healing (2.19 (0.80) vs. 1.16 (0.55) mm, p < 0.001), as well as a higher alteration in the final position of the mid muco-gingival junction (1.73 (1.34) vs. 0.88 (0.88) mm, p < 0.01). CONCLUSION: PRF-L concentrate accelerates wound healing in post-extraction sockets in terms of new mineralized tissue component. However, the use of ß-TCP biomaterial appears to be superior to maintain bucco-lingual volume and the final position of the muco-gingival junction.

Histomorphometric Evaluation of Ridge Preservation With and Without Connective Tissue Graft Over Buccal Plate Using Different Types of Bone Substitute: An Animal Study.

PURPOSE: The aim of this investigation was to assess the efficacy of using subepithelial connective tissue graft (CTG) over the buccal plate in conjunction with 2 different bone graft materials in fresh extraction sites. MATERIALS AND METHODS: Five mongrel dogs were used. Bilateral third (P3) mandibular premolars were extracted atraumatically. Animals were randomly divided in the 4 experimental groups: no CT (NCT) + anorganic bovine bone (ABB), NCT + biphasic calcium phosphate (BCP), CT + ABB, and CT + BCP. This study evaluated tissue healing at 15, 30, 60, 90, and 120 days after socket preservation, using histologic and histomorphometric analyses. RESULTS: The main finding showed that all groups presented similar results with minor differences regardless of the use of CTG and type of bone substitute. A greater amount of residual graft particles was found when ABB was used. No differences in the histologic and histomorphometric analysis were found when comparing the use of CTG with NCTG for ridge preservation procedure. CONCLUSION: Within the limitations of this animal study, the use of CTG to overbuild the buccal plate at time of tooth extraction did not affect the quality of bone regeneration.