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In tissue engineering, three key components are cells, biological/mechanical cues, and scaffolds. Biological cues are normally proteins such as growth factors and their derivatives, bioactive molecules, and the regulators of a gene. Numerous growth factors such as VEGF, FGF, and TGF-ß are being studied and applied in different studies. The carriers used to release these growth factors also play an important role in their functioning. From the early part of the 1990s, more research has beenconductedon the role of fibroblast growth factors on the various physiological functions in our body. The fibroblast growth factor family contains 22 members. Fibroblast growth factors such as 2, 9, and 18 are mainly associated with the differentiation of osteoblasts and in bone regeneration. FGF-18 stimulates the PI3K/ERK pathway and smad1/5/8 pathway mediated via BMP-2 by blocking its antagonist, which is essential for bone formation. FGF-18 incorporated hydrogel and scaffolds had showed enhanced bone regeneration. This review highlights these functions and current trends using this growth factor and potential outcomes in the field of bone regeneration.

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Background: The gold standard for osseointegration remains the autogenous bone graft, but biomaterials such as Beta - tricalcium phosphate (ß - TCP) in its pure-phase showed promising results to be practical bone substitutes. This kind of implants are optimal candidates for bone integration due to their osseoconductive, biocompatibility, bioactivity, and absorptive properties. Methods: A systematic review was conducted using 5 databases (Cochrane Library, PubMed, Scielo, Medline-Bireme and Google Scholar) for searching published studies between January 1st 2011 and June 15th 2021. Only clinical and experimental studies, and case reports were included in this research. Human and animal studies published only in Portuguese or English with clinical, radiologic, and histologic evidence of new bone formation, osseoconduction, and osseointegration were included. This systematic review was reported according to PRISMA guidelines. Results: Approximately 14.554 articles were initially found, but after advanced searching using specific including and excluding keywords, matching Boolean operators "AND," "OR" and "NOT," and after excluding duplicates, a total of 12 articles were included for this systematic review, including experimental works, a retrospective study, a randomized controlled clinical study, a randomized prospective study, a prospective observational study, and a case report. All articles showed 100% effectiveness in bone integration after ß - TCP implantation by clinical, image and/or histologic assessment. Implant shape and porosity seem to have influence in osseointegration process. ß - TCP can give predictable, sustainable, and adequate new bone formation with the least infection rates in implant placement cases and patient morbidity, which is the current goals for bone integration, augmentation and replacement. Conclusion: ß - TCP in its pure-phase is widely used in dentistry and maxillofacial surgery, but there is a lack of information about the use of this biomaterial for filling critical segmental defects of long bones in veterinary medicine. In this area, only experimental studies in small defects were carried out, with no clinical cases performed in animals with a longer observation time. ß - TCP can produce predictable, sustainable, and adequate bone formation, with minimal infection rates and low patient morbidity. But more clinical studies in the future, demonstrating specific metric measurements in relation to bone consolidation, as well as showing results using other shapes of this implant are needed to evaluate further in depth osseoconductive and osseointegrative characteristics of this biomaterial, in order to develop new comparisons and quantitative analyses for its use in veterinary medicine as a bone replacement.

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BACKGROUND: Vascularized bone tissue transfer, commonly used to reconstruct large mandibular defects, is challenged by long operative times, extended hospital stay, donor-site morbidity, and resulting health care. 3D-printed osseoconductive tissue-engineered scaffolds may provide an alternative solution for reconstruction of significant mandibular defects. This pilot study presents a novel 3D-printed bioactive ceramic scaffold with osseoconductive properties to treat segmental mandibular defects in a rabbit model. METHODS: Full-thickness mandibulectomy defects (12 mm) were created at the mandibular body of eight adult rabbits and replaced by 3D-printed ceramic scaffold made of 100% ß-tricalcium phosphate, fit to defect based on computed tomography imaging. After 8 weeks, animals were euthanized, the mandibles were retrieved, and bone regeneration was assessed. Bone growth was qualitatively assessed with histology and backscatter scanning electron microscopy, quantified both histologically and with micro computed tomography and advanced 3D image reconstruction software, and compared to unoperated mandible sections (UMSs). RESULTS: Histology quantified scaffold with newly formed bone area occupancy at 54.3 ± 11.7%, compared to UMS baseline bone area occupancy at 55.8 ± 4.4%, and bone area occupancy as a function of scaffold free space at 52.8 ± 13.9%. 3D volume occupancy quantified newly formed bone volume occupancy was 36.3 ± 5.9%, compared to UMS baseline bone volume occupancy at 33.4 ± 3.8%, and bone volume occupancy as a function of scaffold free space at 38.0 ± 15.4%. CONCLUSIONS: 3D-printed bioactive ceramic scaffolds can restore critical mandibular segmental defects to levels similar to native bone after 8 weeks in an adult rabbit, critical sized, mandibular defect model.

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Biomimetic calcium phosphate coatings have been developed for bone regeneration and repair because of their biocompatibility, osteoconductivity, and easy preparation. They can be rendered osteoinductive by incorporating an osteogenic agent, such as bone morphogenetic protein 2 (BMP-2), into the crystalline lattice work in physiological situations. The biomimetic calcium phosphate coating enables a controlled, slow and local release of BMP-2 when it undergoes cell mediated coating degradation induced by multinuclear cells, such as osteoclasts and foreign body giant cells, which mimics a physiologically similar release mode, to achieve sustained ectopic or orthotopic bone formation. Therefore, biomimetic calcium phosphate coatings are considered to be a promising delivery vehicle for osteogenic agents. In this review, we present an overview of biomimetic calcium phosphate coatings including their preparation techniques, physico-chemical properties, potential as drug carrier, and their pre-clinical application both in ectopic and orthotopic animal models. We briefly review some features of hydroxyapatite coatings and their clinical applications to gain insight into the clinical applications of biomimetic calcium phosphate coatings in the near future.