Large injuries to bones are still one of the most challenging musculoskeletal problems. Tissue engineering can combine stem cells, scaffold biomaterials, and biofactors to aid in resolving this complication. Therefore, this review aims to provide information on the recent advances made to utilize the potential of biomaterials for making bone scaffolds and the assisted stem cell therapy and use of biofactors for bone tissue engineering. The requirements and different types of biomaterials used for making scaffolds are reviewed. Furthermore, the importance of stem cells and biofactors (growth factors and extracellular vesicles) in bone regeneration and their use in bone scaffolds and the key findings are discussed. Lastly, some of the main obstacles in bone tissue engineering and future trends are highlighted.

Background: Apigenin is a plant-derived flavonoid with antioxidative and antiapoptotic effects. Bone marrow stromal cells (BMSCs) are a type of mesenchymal stem cells (MSCs) that may recover damaged ovaries. It seems that apigenin may promote the differentiation of MSCs. Objective: The aim of this study was to investigate the effect of coadministration of apigenin and BMSCs on the function, structure, and apoptosis of the damaged ovaries after creating a chemotherapy model with cyclophosphamide in rat. Materials and Methods: For chemotherapy induction and ovary destruction, cyclophosphamide was injected intraperitoneally to 40 female Wistar rats (weighing 180–200 gr, 10 wk old) for 14 days. Then, the rats were randomly divided into four groups (n = 10/each): control, apigenin, BMSCs and coadministration of apigenin and BMSCs. Injection of apigenin was performed intraperitoneally and BMSC transplantation was performed locally in the ovaries. The level of anti-mullerian hormone serum by ELISA kit, the number of oocytes by superovulation, the number of ovarian follicles in different stages by H&E staining, and the expression of ovarian Bcl-2 and Bax proteins by western blot were assessed after four wk. Results: The results of serum anti-mullerian hormone level, number of oocytes and follicles, and Bcl-2/Bax expression ratio showed that coadministration of apigenin and BMSCs significantly recovered the ovarian function, structure, and apoptosis compared to the control, BMSC, and apigenin groups (p < 0.001). Conclusion: The results suggest that the effect of coadministration of apigenin and BMSCs is maybe more effective than the effect of their administrations individually on the recovery of damaged ovaries following the chemotherapy with cyclophosphamide in rats. Key words: Apigenin, Bone marrow stromal cells, Chemotherapy, Ovary, Regeneration.

Background Three-dimensional (3D) printing is a capable approach for the fabrication of bone tissue scaffolds. Nevertheless, a purely made scaffold such as polylactic acid (PLA) may suffer from shortcomings and be restricted due to its biological behavior. Gelatin, hydroxyapatite and platelet-rich plasma (PRP) have been revealed to be of potential to enhance the osteogenic effect. In this study, it was tried to improve the properties of 3D-printed PLA scaffolds by infilling them with gelatin-nano-hydroxyapatite (PLA/G-nHA) and subsequent coating with PRP. For comparison, bare PLA and PLA/G-nHA scaffolds were also fabricated. The printing accuracy, the scaffold structural characterizations, mechanical properties, degradability behavior, cell adhesion, mineralization, systemic effect of the scaffolds on the liver enzymes, osteocalcin level in blood serum and in vivo bone regeneration capability in rat critical-sized calvaria defect were evaluated. Results High printing accuracy (printing error of < 11%) was obtained for all measured parameters including strut thickness, pore width, scaffold density and porosity%. The highest mean ultimate compression strength (UCS) was associated with PLA/G-nHA/PRP scaffolds, which was 10.95 MPa. A slow degradation rate was observed for all scaffolds. The PLA/G-nHA/PRP had slightly higher degradation rate, possibly due to PRP release, with burst release occurred at week 4. The MTT results showed that PLA/G-nHA/PRP provided the highest cell proliferation at all time points, and the serum biochemistry (ALT and AST level) results indicated no abnormal/toxic influence caused by scaffold biomaterials. Superior cell adhesion and mineralization were obtained for PLA/G-nHA/PRP. Furthermore, all the developed scaffolds showed bone repair capability. The PLA/G-nHA/PRP scaffolds could better support bone regeneration than bare PLA and PLA/G-nHA scaffolds. Conclusion The PLA/G-nHA/PRP scaffolds can be considered as potential for hard tissue repair.

In this paper, the in-vivo healing of critical-sized bony defects by cell-free and stem cell-seeded 3D-printed PLA scaffolds was studied in rat calvaria bone. The scaffolds were implanted in the provided defect sites and histological analysis was conducted after 8 and 12 weeks. The results showed that both cell-free and stem cell-seeded scaffolds exhibited superb healing compared with the empty defect controls, and new bone and connective tissues were formed in the healing site after 8 and 12 weeks, postoperatively. The higher filled area, bone formation and bone maturation were observed after 12 weeks, particularly for PLA + Cell scaffolds.

Background Alumina-titanium (Al2O3-Ti) biocomposites have been recently developed with improved mechanical properties for use in heavily loaded orthopedic sites. Their biological performance, however, has not been investigated yet. Methods The aim of the present study was to evaluate the in vivo biological interaction of Al2O3-Ti. Spark plasma sintering (SPS) was used to fabricate Al2O3-Ti composites with 25 vol.%, 50 vol.%, and 75 vol.% Ti content. Pure alumina and titanium were also fabricated by the same procedure for comparison. The fabricated composite disks were cut into small bars and implanted into medullary canals of rat femurs. The histological analysis and scanning electron microscopy (SEM) observation were carried out to determine the bone formation ability of these materials and to evaluate the bone-implant interfaces. Results The histological observation showed the formation of osteoblast, osteocytes with lacuna, bone with lamellar structures, and blood vessels indicating that the healing and remodeling of the bone, and vasculature reconstruction occurred after 4 and 8 weeks of implantation. However, superior bone formation and maturation were obtained after 8 weeks. SEM images also showed stronger interfaces at week 8. There were differences between the composites in percentages of bone area (TB%) and the number of osteocytes. The 50Ti composite showed higher TB% at week 4, while 25Ti and 75Ti represented higher TB% at week 8. All the composites showed a higher number of osteocytes compared to 100Ti, particularly 75Ti. Conclusions The fabricated composites have the potential to be used in load-bearing orthopedic applications.