Osteogenic enhancement of modular ceramic nanocomposites impregnated with human dental pulp stem cells: an approach for bone repair and regenerative medicine.

BACKGROUND/AIM: Human dental pulp-derived mesenchymal stem cells (hDP-MSCs) are a promising source of progenitor cells for bone tissue engineering. Nanocomposites made of calcium phosphate especially hydroxyapatite (HA) offer an impressive solution for orthopedic and dental implants. The combination of hDP-MSCs and ceramic nanocomposites has a promising therapeutic potential in regenerative medicine. Despite the calcium phosphate hydroxyapatite (HA)-based nanocomposites offer a good solution for orthopedic and dental implants, the heavy load-bearing clinical applications require higher mechanical strength, which is not of the HA' properties that have low mechanical strength. Herein, the outcomes of using fabricated ceramic nanocomposites of hydroxyapatite/titania/calcium silicate mixed at different ratios (C1, C2, and C3) and impregnated with hDP-MSCs both in in vitro cultures and rabbit model of induced tibial bone defect were investigated. Our aim is to find out a new approach that would largely enhance the osteogenic differentiation of hDP-MSCs and has a therapeutic potential in bone regeneration. SUBJECTS AND METHODS: Human DP-MSCs were isolated from the dental pulp of the third molar and cultured in vitro. Alizarin Red staining was performed at different time points to assess the osteogenic differentiation. Flow cytometer was used to quantify the expression of hDP-MSCs unique surface markers. Rabbits were used as animal models to evaluate the therapeutic potential of osteogenically differentiated hDP-MSCs impregnated with ceramic nanocomposites of hydroxyapatite/tatiana/calcium silicate (C1, C2, and C3). Histopathological examination and scanning electron microscopy (SEM) were performed to evaluate bone healing potential in the rabbit induced tibial defects three weeks post-transplantation. RESULTS: The hDP-MSCs showed high proliferative and osteogenic potential in vitro culture. Their osteogenic differentiation was accelerated by the ceramic nanocomposites' scaffold and revealed bone defect's healing in transplanted rabbit groups compared to control groups. Histopathological and SEM analysis of the transplanted hDP-MSCs/ceramic nanocomposites showed the formation of new bone filling in the defect area 3 weeks post-implantation. Accelerate osseointegration and enhancement of the bone-bonding ability of the prepared nanocomposites were also confirmed by SEM. CONCLUSIONS: The results strongly suggested that ceramic nanocomposites of hydroxyapatite/ titania /calcium silicate (C1, C2, and C3) associated with hDP-MSCs have a therapeutic potential in bone healing in a rabbit model. Hence, the combined osteogenic system presented here is recommended for application in bone tissue engineering and regenerative medicine.

Combination of Human Amniotic Fluid Derived-Mesenchymal Stem Cells and Nano-hydroxyapatite Scaffold Enhances Bone Regeneration.

BACKGROUND: Human amniotic fluid-derived stem cells (hAF-MSCs) have a high proliferative capacity and osteogenic differentiation potential in vitro. The combination of hAF-MSCs with three-dimensional (3D) scaffold has a promising therapeutic potential in bone tissue engineering and regenerative medicine. Selection of an appropriate scaffold material has a crucial role in a cell supporting and osteoinductivity to induce new bone formation in vivo. AIM: This study aimed to investigate and evaluate the osteogenic potential of the 2nd-trimester hAF-MSCs in combination with the 3D scaffold, 30% Nano-hydroxyapatite chitosan, as a therapeutic application for bone healing in the induced tibia defect in the rabbit. SUBJECT AND METHODS: hAF-MSCs proliferation and culture expansion was done in vitro, and osteogenic differentiation characterisation was performed by Alizarin Red staining after 14 & 28 days. Expression of the surface markers of hAF-MSCs was assessed using Flow Cytometer with the following fluorescein-labelled antibodies: CD34-PE, CD73-APC, CD90-FITC, and HLA-DR-FITC. Ten rabbits were used as an animal model with an induced defect in the tibia to evaluate the therapeutic potential of osteogenic differentiation of hAF-MSCs seeded on 3D scaffold, 30% Nano-hydroxyapatite chitosan. The osteogenic differentiated hAF-MSCs/scaffold composite system applied and fitted in the defect region and non-seeded scaffold was used as control. The histopathological investigation was performed at 2, 3, & 4 weeks post-transplantation and scanning electron microscope (SEM) was assessed at 2 & 4 weeks post-transplantation to evaluate the bone healing potential in the rabbit tibia defect. RESULTS: Culture and expansion of 2nd-trimester hAF-MSCs presented high proliferative and osteogenic potential in vitro. Histopathological examination for the transplanted hAF-MSCs seeded on the 3D scaffold, 30% Nano-hydroxyapatite chitosan, demonstrated new bone formation in the defect site at 2 & 3 weeks post-transplantation as compared to the control (non-seeded scaffold). Interestingly, the scaffold accelerated the osteogenic differentiation of AF-MSCs and showed complete bone healing of the defect site as compared to the control (non-seeded scaffold) at 4 weeks post-transplantation. Furthermore, the SEM analysis confirmed these findings. CONCLUSION: The combination of the 2nd-trimester hAF-MSCs and 3D scaffold, 30% Nano-hydroxyapatite chitosan, have a therapeutic perspective for large bone defect and could be used effectively in bone tissue engineering and regenerative medicine.

Osteogenic Differentiation Potential of Human Bone Marrow and Amniotic Fluid-Derived Mesenchymal Stem Cells in Vitro & in Vivo.

BACKGROUND: Cell therapies offer a promising potential in promoting bone regeneration. Stem cell therapy presents attractive care modality in treating degenerative conditions or tissue injuries. The rationale behind this is both the expansion potential of stem cells into a large cell population size and its differentiation abilities into a wide variety of tissue types, when given the proper stimuli. A progenitor stem cell is a promising source of cell therapy in regenerative medicine and bone tissue engineering. AIM: This study aimed to compare the osteogenic differentiation and regenerative potentials of human mesenchymal stem cells derived from human bone marrow (hBM-MSCs) or amniotic fluid (hAF-MSCs), both in vitro and in vivo studies. SUBJECTS AND METHODS: Human MSCs, used in this study, were successfully isolated from two human sources; the bone marrow (BM) and amniotic fluid (AF) collected at the gestational ages of second or third trimesters. RESULTS: The stem cells derived from amniotic fluid seemed to be the most promising type of progenitor cells for clinical applications. In a pre-clinical experiment, attempting to explore the therapeutic application of MSCs in bone regeneration, Rat lumbar spines defects were surgically created and treated with undifferentiated and osteogenically differentiated MSCs, derived from BM and second trimester AF. Cells were loaded on gel-foam scaffolds, inserted and fixed in the area of the surgical defect. X-Ray radiography follows up, and histopathological analysis was done three-four months post- operation. The transplantation of AF-MSCs or BM-MSCs into induced bony defects showed promising results. The AF-MSCs are offering a better healing effect increasing the likelihood of achieving successful spinal fusion. Some bone changes were observed in rats transplanted with osteoblasts differentiated cells but not in rats transplanted with undifferentiated MSCs. Longer observational periods are required to evaluate a true bone formation. The findings of this study suggested that the different sources; hBM-MSCs or hAF-MSCs exhibited remarkably different signature regarding the cell morphology, proliferation capacity and osteogenic differentiation potential. CONCLUSIONS: AF-MSCs have a better performance in vivo bone healing than that of BM-MSCs. Hence, AF derived MSCs is highly recommended as an alternative source to BM-MSCs in bone regeneration and spine fusion surgeries. Moreover, the usage of gel-foam as a scaffold proved as an efficient cell carrier that showed bio-compatibility with cells, bio-degradability and osteoinductivity in vivo.

Stress analysis of mandibular implant overdentures retained with one, two, or four ball attachments: A finite element study.

BACKGROUND: The aim of this study is to compare stress patterns induced by ball attachments when used to retain mandibular overdentures supported by one, two, or four dental implants. MATERIALS AND METHODS: In this finite element study, three 3D models were prepared to simulate mandibular implant overdentures retained by one or two or four ball attachments of 3.5 mm diameter with collar height 1.6 mm. The geometric solid models were created by commercial engineering computer-aided design package then transferred to ANSYS as set of standard ACIS text files. Vertical load of 100 N was applied on the central fossa of the right molar. Stresses were evaluated at the areas of implant and attachment components, mucosa underlying overdentures, and cortical and cancellous bone adjacent to implants. RESULTS: The results of this study showed that the Von Mises stresses generated by the application of vertical loading varied according to the number of implants used to support the overdenture. Maximum Von Mises stress on cortical bone ranged between 1.15 and 1.77 MPa in all-studied cases. Mucosa was squeezed under the one implant model. Flexibility of the overdenture material played a significant role in distributing the load stress and deformation of all underlying structure. Caps deformation was the highest when using two implants. CONCLUSION: With increasing the number of implants, stresses and deformations of overdenture are reduced, but implants receive greater stresses and deformations. Using two implants in the canine region showed the best results when compared with using one or four implants, except for the caps.

Neuroendocrine tumors of the lung: A five-year retrospective experience of Egyptian NCI (2010-2014).

BACKGROUND: The spectrum of lung neuroendocrine tumors (NETs) encompasses low grade typical carcinoid (TC), intermediate grade atypical carcionid (AC) and high grade, both large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC), with extreme differences in management and survival. OBJECTIVE: To study clinicopathologic and prognostic factors affecting survival of lung NETs. PATIENTS AND METHODS: This is a retrospective study evaluating 35 patients with primary lung NETs treated at National Cancer Institute of Egypt (NCI-E) between January 2010 and December 2014. Pathological diagnosis depended on definite morphology and positivity to at least one of the neuroendocrine markers by immunohistochemistry. RESULTS: The mean age of the patients was 53 ±â€¯11.2 years with male predominance. Performance status (PS) I was encountered in 48.6%. SCLC was the prevalent histology in 68.6%, followed by LCNEC & TC in 20 & 11.4%, respectively. Curative surgery was employed in 100 & 57% of TC & LCNEC patients, respectively. Stage IV was anticipated in 87.5 & 43% of SCLC & LCNEC, respectively. For the entire cohort, the median event-free survival (EFS) and overall survival (OS) were 8.0 and 13.7 months, respectively, whereas the 3-year EFS and OS were 17.8 & 20%, respectively. SCLC patients showed significantly the worst OS compared to other NETs (p = 0.001). Patients who presented with stage IV and PS > I demonstrated significantly shorter OS than those with locoregional and PS I (p = 0.00001 &p = 0.002, respectively). CONCLUSIONS: SCLC subtype, stage IV and initial PS > I are poor prognostic factors for lung NETs associated with shorter survival. This conclusion needs to be confirmed by larger studies.

Effect of combination of fractional CO2 laser and narrow-band ultraviolet B versus narrow-band ultraviolet B in the treatment of non-segmental vitiligo.

The present study was designed to evaluate the effect of combining fractional CO2 laser with narrow-band ultraviolet B (NB-UVB) versus NB-UVB in the treatment of non-segmental vitiligo. The study included 20 patients with non-segmental stable vitiligo. They were divided into two groups. Group I received a single session of fractional CO2 laser therapy on the right side of the body followed by NB-UVB phototherapy twice per week for 8 weeks. Group II received a second session of fractional CO2 laser therapy after 4 weeks from starting treatment with NB-UVB. The vitiligo lesions were assessed before treatment and after 8 weeks of treatment by VASI. At the end of the study period, the vitiligo area score index (VASI) in group I decreased insignificantly on both the right (-2.6%) and left (-16.4%) sides. In group II, VASI increased insignificantly on the right (+14.4%) and left (+2.5%) sides. Using Adobe Photoshop CS6 extended program to measure the area of vitiligo lesions, group I showed a decrease of -1.02 and -6.12% in the mean area percentage change of vitiligo lesions on the right and left sides, respectively. In group II the change was +9.84 and +9.13% on the right and left sides, respectively. In conclusion, combining fractional CO2 laser with NB-UVB for the treatment of non-segmental vitiligo did not show any significant advantage over treatment with NB-UVB alone. Further study of this combination for longer durations in the treatment of vitiligo is recommended.

New dental implant selection criterion based on implant design.

OBJECTIVE: A comparative study between threaded and plain dental implant designs was performed to find out a new criterion for dental implant selection. MATERIALS AND METHODS: Several dental implant designs with a systematic increase in diameter and length were positioned in a cylindrical-shaped bone section and analyzed using finite element method. Four loading types were tested on different dental implant designs; tension of 50 N, compression of 100 N, bending of 20 N, and torque of 2 Nm, to derive design curves. RESULTS: Better stress distribution on both spongy and cortical bone was noted with an increase in dental implant diameter and length. With the increase in dental implant side area, a stress reduction in the surrounding bones was observed, where threaded dental implants showed better behavior over the plain ones. CONCLUSIONS: Increasing value of ratio between dental implant side area and its cross-sectional area reduces stresses transferred to cortical and spongy bones. The use of implants with higher ratio of side area to cross-section area, especially with weak jaw bone, is recommended.

Bone Height Changes of the Mandibular Edentulous Ridge in Screw Retained Versus Telescopic Restorations for Completely Edentulous Patients.

AIM: This study was established to evaluate the amount of bone height changes in the posterior mandibular area of edentulous patients receiving screw-retained prostheses versus removable telescopic implant overdentures. MATERIAL AND METHODS: Every patient received four inter-foraminal implants regarding the mandibular arch and four anterior implants for the maxillary arch, computer guided surgical guides were planned for the insertion of the implants accurately with a flapless technique. Panoramic radiographs were made immediately, six months and twelve months after the prostheses` use proportional area and vertical measurements were applied to determine changes in the bone height of the posterior mandibular edentulous area. RESULTS: After twelve months, a statistically non-significant amount of bone resorption was reported for both groups. CONCLUSION: Up to the limitations of this study both treatment options the screw retained and telescopic overdenture can be used for rehabilitation of completely edentulous patients. These cases must be followed for a longer period to have a definite answer regarding their efficiency in the long run.

The Biomechanical Effect of Different Denture Base Materials on the Articular Disc in Complete Denture Wearers: A Finite Element Analysis.

AIM: The objective of the present study was to evaluate the effect of different denture base materials on the stress distribution in TMJ articular disc (AD) in complete denture wearers. MATERIAL AND METHODS: A three dimensional Finite Element (FEA) models of an individual temporomandibular joint (TMJ) was built on the basis CT scan. The FEA model consisted of four parts: the condyle, the articular disc, the denture base, and the articular eminence skull. Acrylic resin and chrome-cobalt denture base materials were studied. Static loading of 300N was vertically applied to the central fossa of the mandibular second premolar. Stress and strain were calculated to characterize the stress/strain patterns in the disc. RESULTS: The maximum tensile stresses were observed in the anterior and posterior bands of (AD) on load application with the two denture base materials. The superior boundaries of the glenoid fossa showed lower stress than those on the inferior boundaries facing the condyle. CONCLUSIONS: Within the limitations of the present study it may be concluded that: The denture base material may have an effect in stress-strain pattern in TMJ articular disc. The stiffer denture base material, the better the distribution of the load to the underling mandibular supporting structures & reducing stresses induced in the articular disc.

Ultrasound biomicroscopy in the diagnosis of skin diseases.

Ultrasound scanning is becoming an important diagnostic tool in dermatology. The major advantages of this technique are its non invasive non-ionizing nature and its relatively low cost. We aimed to evaluate the accuracy of ultrasound biomicroscopy (UBM) in the diagnosis of eight skin disorders namely, morphea, keloid, lichen planus, chronic eczema, psoriasis, port wine stain, seborrheic keratosis, and photo-aged skin, through correlation of its findings with clinical and pathological assessment. Fifty seven patients with the above diseases were examined by ultrasound biomicroscopy (UBM). Two areas, one of normal skin and the other from lesional skin, were examined for each patient. Skin biopsies were taken from the same lesion examined by UBM. In morphea, the dermal echogenicity was increased and the thickness of morphea plaques correlated significantly with disease severity. Keloids appeared as low echogenic images. In lichen planus and chronic eczema the dermis appeared as sound shadow. In psoriasis, an intermediate zone between the epidermis and dermis (B zone) was detected. Its thickness correlated significantly with the PASI score. Port wine stain lesions appeared hypoechoic. Seborrheic keratosis appeared as a sound shadow. In photo-aged skin a subepidermal low echogenic band (SLEB) was detected. We conclude that UBM is a non-invasive diagnostic tool in dermatology which can be used to give valuable information about disease progress and the effectiveness of therapy.