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

Tissue engineering is a relatively recent research area aimed at developing artificial tissues that can restore, maintain, or even improve the anatomical and/or functional integrity of injured tissues. Otolaryngology, as a leading surgical specialty in head and neck surgery, is a candidate for the use of these advanced therapies and medicinal products developed. Nevertheless, a knowledge-based analysis of both areas together is still needed. The dataset was retrieved from the Web of Science database from 1900 to 2020. SciMAT software was used to perform the science mapping analysis and the data for the biomedical translation identification was obtained from the iCite platform. Regarding the analysis of the cognitive structure, we find consolidated research lines, such as the generation of cartilage for use as a graft in reconstructive surgery, reconstruction of microtia, or the closure of perforations of the tympanic membrane. This last research area occupies the most relevant clinical translation with the rest of the areas presenting a lower translational level. In conclusion, Tissue engineering is still in an early translational stage in otolaryngology, otology being the field where most advances have been achieved. Therefore, although otolaryngologists should play an active role in translational research in tissue engineering, greater multidisciplinary efforts are required to promote and encourage the translation of potential clinical applications of tissue engineering for routine clinical useUniversidad Peruana de Ciencias Aplicadas, Lima, Perú (UPC-ExPost-2023-2)The PECART-0027-2020 (Consejería de Salud y Familias, Junta de Andalucía, Spain)ProyExcel_00875 (Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía, Spain)Research Group #CTS-1028 (MP-M and PG-M, Junta de Andalucía, Spain

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 (_ β-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 _-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 β-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 β-TCP biomaterial appears to be superior to maintain bucco-lingual volume and the final position of the muco-gingival junction.The authors of this manuscript were partially supported by Research Groups #CTS-138 (FO) and #CTS-1028 (PGM, MPM) (Junta de Andalucía, Spain). Grafting materials were generously provided by Dentium Co., Ltd., Seoul, Korea

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

The authors are partially supported by funding from Research Groups #CTS-138 and #CTS-1028 (Junta de Andalucía, Spain). Funding for open access charge: Universidad de Granada / CBUA.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.Junta de Andalucía #CTS-138, #CTS-1028Universidad de Granada / CBU

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

This is the peer reviewed version of the following article: [Olaechea A, Mendoza-Azpur G, O Valle F, Padial-Molina M, Martin-Morales N, Galindo-Moreno P. Biphasic hydroxyapatite and ß-tricalcium phosphate biomaterial behavior in a case series of maxillary sinus augmentation in humans. Clin Oral Implants Res. 2019 Apr;30(4):336-343. doi: 10.1111/clr.13419.], which has been published in final form at [https://doi.org/10.1111/clr.13419]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.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.Junta de Andalucía #CTS-138 and #CTS-102

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.Consejería de Transformación Económica, Industria, Conocimiento y UniversidadesRevisión por pare

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 (&#946;-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 &#946;-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 &#946;-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 &lt; 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 &lt; 0.01). Conclusion: PRF-L concentrate accelerates wound healing in post-extraction sockets in terms of new mineralized tissue component. However, the use of &#946;-TCP biomaterial appears to be superior to maintain bucco-lingual volume and the final position of the muco-gingival junction