3D printed polylactic acid/gelatin-nano-hydroxyapatite/platelet-rich plasma scaffold for critical-sized skull defect 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.

Sesamol protects the function and structure of rat ovaries against side effects of cyclophosphamide by decreasing oxidative stress and apoptosis.

AIM: Chemotherapy with cyclophosphamide can damage ovaries and cause infertility in girls and women. Sesamol is a phenolic antioxidant that can protect various organs from damage. The purpose of this study was to evaluate the effects of sesamol on protecting the function and structure of rat ovaries against the side effects of a chemotherapy model with cyclophosphamide. METHODS: Twenty-four adult female Wistar rats were randomly divided into three groups: (1) normal group, without any treatment, (2) control group, immediately after receiving cyclophosphamide, 0.5% dimethyl sulfoxide (DMSO) as the solvent of sesamol was intraperitoneally injected for 14 consecutive days, (3) sesamol group, immediately after receiving cyclophosphamide, 50 mg/kg sesamol was intraperitoneally injected for 14 consecutive days. Four weeks after the last injection, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in the ovary, anti-Mullerian hormone (AMH) levels in the serum, number of ovarian follicles in different stages, and expression of proteins growth differentiation factor-9 (GDF-9), Bcl-2, and Bax in the ovary were evaluated. RESULTS: The results of SOD activity and MDA levels in the ovary, AMH levels in the serum, number of ovarian follicles in different stages, and expression of proteins GDF9, Bcl-2, and Bax in the ovary were significantly more favorable in the sesamol group than the control group. CONCLUSIONS: The results suggest that sesamol may protect function and structure in the rat ovaries against side effects of the chemotherapy model with cyclophosphamide by decreasing oxidative stress and apoptosis in the ovary.

Reviewing the role of cardiac exosomes in myocardial repair at a glance.

Exosome-based therapy is an emerging novel approach for myocardial infarction (MI) treatment. Exosomes are identified as extracellular vesicles that are produced within multivesicular bodies in the cells' cytosols and then are secreted from the cells. Exosomes are 30-100 nm in diameter that are released from viable cells and are different from other secreted vesicles such as apoptotic bodies and microvesicles in their origin and contents such as RNAs, proteins, and nucleic acid. The recent advances in exosome research have demonstrated the role of these bionanovesicles in the physiological, pathological, and molecular aspects of the heart. The results of in vitro and preclinical models have shown that exosomes from different cardiac cells can improve cardiac function following MI. For example, mesenchymal stem cells (MSCs) and cardiac progenitor cells (CPCs) containing exosomes can affect the proliferation, survival, and differentiation of cardiac fibroblasts and cardiomyocytes. Moreover, MSCs- and CPCs-derived exosomes can enhance the migration of endothelial cells. Exosome-based therapy approaches augment the cardiac function by multiple means, such as reducing fibrosis, stimulation of vascular angiogenesis, and proliferation of cardiomyocytes that result in replacing damaged heart tissue with newly generated functional myocytes. This review article aims to briefly discuss the recent advancements in the role of secreted exosomes in myocardial repair by focusing on cardiac cells-derived exosomes.

Decellularization and characterization of camel pericardium as a new scaffold for tissue engineering and regenerative medicine.

BACKGROUND: Valvular heart diseases (VHDs) have become prevalent in populations due to aging. Application of different biomaterials for cardiac valve regeneration and repair holds a great promise for treatment of VHD. Aortic valve replacement using tissue-engineered xenografts is a considered approach, and the pericardium of different species such as porcine and bovine has been studied over the last few years. It has been suggested that the animal origin can affect the outcomes of replacement. METHODS: So, herein, we at first decellularized and characterized the camel pericardium (dCP), then characterized dCP with H&E staining, in vitro and in vivo biocompatibility and mechanical tests and compared it with decellularized bovine pericardium (dBP), to describe the potency of dCP as a new xenograft and bio scaffold. RESULTS: The histological assays indicated less decluttering and extracellular matrix damage in dCP after decellularization compared to the dBP also dCP had higher Young Modulus (105.11), and yield stress (1.57 ± 0.45). We observed more blood vessels and also less inflammatory cells in the dCP sections after implantation. CONCLUSIONS: In conclusion, the results of this study showed that the dCP has good capabilities not only for use in VHD treatment but also for other applications in tissue engineering and regenerative medicine.

Bone marrow stromal cell-conditioned medium regenerates injured sciatic nerve by increasing expression of MPZ and NGF and decreasing apoptosis.

Objectives: Despite the many benefits of mesenchymal stem cell (MSC) transplantation for tissue regeneration, there are some limitations to using them, including the high costs, applying invasive procedures, the possibility of transplant rejection, and cell malignancy. This study aimed to investigate the effect of secretions of bone marrow stromal cells (BMSCs) with the cell-free strategy on damaged sciatic nerve with an emphasis on the role of apoptosis and the expression of myelin protein zero (MPZ) and nerve growth factor (NGF) proteins. Materials and Methods: BMSCs were cultured and a 25-fold concentrated conditioned medium (CM) from the cells was provided. After creating a crush injury in the left sciatic nerve of male rats, BMSCs or CM were injected into the injured site of the nerve. Four weeks later, the expression of MPZ, NGF, Bax, and Bcl-2 proteins in the sciatic nerve and histological parameters of the sciatic nerve and gastrocnemius muscle were assessed. Results: The results demonstrated that injection of CM decreased apoptosis and increased expression of MPZ and NGF proteins, improving remyelination and regeneration of the sciatic nerve almost as much as the transplantation of the BMSCs themselves compared to the control group. Conclusion: The results suggest that BMSC secretions may improve remyelination and regeneration of damaged sciatic nerve by increasing the expression of MPZ and NGF and decreasing apoptosis.

The healing of bone defects by cell-free and stem cell-seeded 3D-printed PLA tissue-engineered scaffolds.

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.

Effect of sesamol on damaged peripheral nerves: Evaluation of functional, histological, molecular, and oxidative stress parameters.

Objective: Peripheral nerve injury is a clinical problem that may cause sensory and motor inabilities. Sesamol is an antioxidant that can help in repairing damaged central nervous system (CNS) and other organs. The present study aimed to investigate whether the antioxidant effects of sesamol could improve the function, structure, and myelination in rats' damaged peripheral nervous system (PNS). Materials and Methods: In this study, 28 adult male Wistar rats were randomly divided into four groups. In the sham group, the sciatic nerve was exposed and restored to its place without inducing crush injury. The control received DMSO (solvent) and the two experimental groups received 50 or 100 mg/kg sesamol intraperitoneally for 28 days after sciatic nerve crush injury, respectively. Next, sciatic function index (SFI), superoxide dismutase (SOD) activity, malondialdehyde (MDA) level, expression of nerve growth factor (NGF) and myelin protein zero (MPZ) proteins in the sciatic nerve, and histological indices of the sciatic nerve and gastrocnemius muscle were evaluated. Results: The results showed that sesamol reduced oxidative stress parameters, increased expression of NGF and MPZ proteins, and improved function and regeneration of the damaged sciatic nerve. Furthermore, a significant regeneration was observed in the gastrocnemius muscle after treatment with sesamol. Although administration of both doses of sesamol was useful, the 100 mg/kg dose was more effective than the 50 mg/kg one. Conclusion: The results suggest that sesamol may be effective in improving damaged peripheral nerves in rats by reducing oxidative stress and increasing the expression of NGF and MPZ proteins.

In vivo performance of Al2O3-Ti bone implants in the rat femur.

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.

Bone Scaffolds: An Incorporation of Biomaterials, Cells, and Biofactors.

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.

Impact of coadministration of apigenin and bone marrow stromal cells on damaged ovaries due to chemotherapy in rat: An experimental study.

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.