Photobiomodulation Can Prevent Medication-Related Osteonecrosis of the Jaw Formation in Tooth Extraction Site of Rat Model.

Objective: This study aims to explore the preventive potential of photobiomodulation (PBM) in bisphosphonate-related osteonecrosis of the jaw (BRONJ) using a rat model. Methods: An experimental rat model was established, exposing rats to zoledronic acid (ZA), a primary risk factor for BRONJ. An 810 nm diode laser was applied with parameters of 0.33 W/cm2 power density and 10 J/cm2 energy density for 30 sec. PBM was initiated 1 day pre-extraction and continued for 2 weeks. The impact of PBM on wound healing in both soft and hard tissues was evaluated post tooth extraction. Results: ZA exposure hindered wound healing in both soft and hard tissues after tooth extraction. PBM intervention effectively mitigated the adverse effects of ZA, promoting healing processes in both tissue types. This suggests the potential of PBM as a preventive strategy for BRONJ in patients on long-term bisphosphonate treatment. Moreover, PBM exhibited enhanced wound healing in normal rats, indicating its broader applicability beyond BRONJ cases. Conclusions: PBM shows promise in preventing and improving wound healing in BRONJ and normal cases. These findings underscore the significance of optimizing PBM parameters and suggest its potential clinical relevance as a preventive intervention for BRONJ and a promoter of wound healing.

Addition of Bone-Marrow Mesenchymal Stem Cells to 3D-Printed Alginate/Gelatin Hydrogel Containing Freeze-Dried Bone Nanoparticles Accelerates Regeneration of Critical Size Bone Defects.

A 3D-printed biodegradable hydrogel, consisting of alginate, gelatin, and freeze-dried bone allograft nanoparticles (npFDBA), is developed as a scaffold for enhancing cell adhesion, proliferation, and osteogenic differentiation when combined with rat bone marrow mesenchymal stem cells (rBMSCs). This composite hydrogel is intended for the regeneration of critical-sized bone defects using a rat calvaria defect model. The behavior of rBMSCs seeded onto the scaffold is evaluated through scanning electron microscope, MTT assays, and quantitative real-time PCR. In a randomized study, thirty rats are assigned to five treatment groups: 1) rBMSCs-loaded hydrogel, 2) rBMSCs-loaded FDBA microparticles, 3) hydrogel alone, 4) FDBA alone, and 5) an empty defect serving as a negative control. After 8 weeks, bone regeneration is assessed using H&E, Masson's trichrome staining, and immunohistochemistry. The 3D-printed hydrogel displays excellent adhesion, proliferation, and differentiation of rBMSCs. The rBMSCs-loaded hydrogel exhibits comparable new bone regeneration to the rBMSCs-loaded FDBA group, outperforming other groups with statistical significance (P-value < 0.05). These findings are corroborated by Masson's trichrome staining and osteocalcin expression. The rBMSCs-loaded 3D-printed hydrogel demonstrates promising potential for significantly enhancing bone regeneration, surpassing the conventional clinical approach (FDBA).

Prefabrication technique by preserving a muscular pedicle from masseter muscle as an in vivo bioreactor for reconstruction of mandibular critical-sized bone defects in canine models.

In vivo bioreactors serve as regenerative niches that improve vascularization and regeneration of bone grafts. This study has evaluated the masseter muscle as a natural bioreactor for ßTCP or PCL/ßTCP scaffolds, in terms of bone regeneration. The effect of pedicle preservation, along with sole, or MSC- or rhBMP2-combined application of scaffolds, has also been studied. Twenty-four mongrel dogs were randomly placed in six groups, including ßTCP, ßTCP/rhBMP2, ßTCP/MSCs, PCL/ßTCP, PCL/ßTCP/rhBMP2, and PCL/ßTCP/MSCs. During the first surgery, the scaffolds were implanted into the masseter muscle for being prefabricated. After 2 months, each group was divided into two subgroups prior to mandibular bone defect reconstruction; one with a preserved vascularized pedicle and one without. After 12 weeks, animals were euthanized, and new bone formation was evaluated using histological analysis. Histological analysis showed that all ß-TCP scaffold groups had resulted in significantly greater rates of new bone formation, either with a pedicle surgical approach or non-pedicle surgical approach, comparing to their parallel groups of ßTCP/PCL scaffolds (p ≤ .05). Pedicled ß-TCP scaffold groups that were treated with either rhBMP2 (48.443% ± 0.250%) or MSCs (46.577% ± 0.601%) demonstrated the highest rates of new bone formation (p ≤ .05). Therefore, masseter muscle can be used as a local in vivo bioreactor with potential clinical advantages in reconstruction of human mandibular defects. In addition, scaffold composition, pedicle preservation, and treatment with MSCs or rhBMP2, influence new bone formation and scaffold degradation rates in the prefabrication technique.

Multi-walled carbon nanotube/hydroxyapatite nanocomposite with leukocyte- and platelet-rich fibrin for bone regeneration in sheep model.

BACKGROUND: The aim of this study was to evaluate the effects of multi-walled carbon nanotubes/hydroxyapatite (MWCNT/HA) granules with or without leukocyte- and platelet-rich fibrin (L-PRF) on bone regeneration in cancellous bone of sheep model. METHODS: Totally, 32 cylindrical holes were drilled in female sheep (n = 4) in the distal epiphysis and proximal metaphysis of right and left humerus and femur. The defects were randomly filled with (1) MWCNT/HA, (2) MWCNT/HA mixed with L-PRF, (3) L-PRF, and (4) left empty as control. After 8 weeks, defects were evaluated and compared radiographically using multi-slice computed tomographic (CT) scan and cone beam CT scans, histologically and histomorphometrically. RESULTS: The results showed that there was no significant inflammation (> 10%) or foreign body reaction around the granules. The new lamellar bone was regenerated around the MWCNT/HA nanocomposite granules. Addition of L-PRF to MWCNT/HA demonstrated significantly improvement of new bone formation, about 27.40 ± 1.08%, in comparison with the L-PRF alone, about (12.16 ± 1.46%) (P < 0.01). Also, the rate of new bone formation was significantly greater with the use of MWCNT/HA granules (24.59 ± 1.54%) compared to the control (10.36 ± 1.17%) (P < 0.01). CONCLUSION: Consequently, both biocompatibility and osteoconductivity of MWCNT/HA nanocomposite were demonstrated in the preclinical sheep model, and the use of L-PRF in combination with MWCNT/HA nanocomposite can improve bone regeneration.

Reconstruction of bilateral ramus-condyle unit defect using custom titanium prosthesis with preservation of both condyles.

BACKGROUND: Novel technologies for management and reconstruction of complex bony defects regarding both function and facial appearance are interestingly used in maxillofacial surgery. In the current study, we demonstrated reconstruction of a bilateral ramus-condyle unit (RCU) defect while preserving both condyles by a novel designed titanium prosthesis using virtual surgical planning (VSP), computer-aided design and manufacturing (CAD/CAM), and Selective Laser Melting (SLM) technologies. MATERIALS AND METHODS: A 3D customized titanium prosthesis was designed for a 49 -year-old patient with bilateral mandibular aggressive central giant cell granuloma (CGCG) according to mandibular normal anatomy and structure while preserving bilateral intact condyles. Finite element study was performed to investigate the effects of new design strength and the stress shielding phenomenon. The design of macro-pores inside the body of prosthesis allowed it to act as a scaffold for bone tissue engineering under load bearing conditions. RESULTS: Analysis of the strength and stress shielding phenomenon demonstrated favorable outcomes regarding the novel design. For instance, there was no stress shielding in any of the preserved condyles with regard to the size and distribution of stresses. Also, the stress distribution around the pores showed that these pores had no effect on the strength of the prosthesis. Thirty month follow-ups after reconstruction of bilateral RCU defect showed normal jaw function with a favorable facial appearance and mandibular contour. CONCLUSION: We design a novel patient-specific prosthesis with desirable biomechanical features for reconstruction of bilateral RCU defect after resection of the benign tumor with preservation of bilateral intact condyles.

Fabrication and Characterization of Nanofibrous Poly (L-Lactic Acid)/Chitosan-Based Scaffold by Liquid-Liquid Phase Separation Technique for Nerve Tissue Engineering.

Fabrication method is one of the essential factors which directly affect on the properties of scaffold. Several techniques have been well established to fabricate nanofibrous scaffolds such as electrospinning. However, preparing a three-dimensional (3-D) interconnected macro-pore scaffold essential for transporting the cell metabolites and nutrients is difficult using the electrospinning method. The main aim of this study was developing a highly porous scaffold by poly (L-lactic acid) (PLLA)/chitosan blend using liquid-liquid phase separation (LLPS) technique, a fast and cost-benefit method, in order to use in nerve tissue engineering. In addition, the effect of different polymeric concentrations on morphology, mechanical properties, hydrophilicity, in vitro degradation rate and pH alteration of the scaffolds were evaluated. Moreover, cell attachment, cell viability and cell proliferation of scaffolds as candidates for nerve tissue engineering was investigated. PLLA/chitosan blend not only had desirable structural properties, porosity, hydrophilicity, mechanical properties, degradation rate and pH alteration but also provided a favorable environment for attachment, viability, and proliferation of human neuroblastoma cells, exhibiting significant potential for nerve tissue engineering applications. However, the polymeric concentration in blend fabrication had influence on both characteristics and cell responses. It concluded that PLLA/chitosan nanofibrous 3-D scaffold fabricated by LLPS method as a suitable candidate for nerve tissue engineering.

Effects of Platelet-Rich Fibrin/Collagen Membrane on Sciatic Nerve Regeneration.

ABSTRACT: Alternative treatment approaches to improve the regeneration ability of damaged peripheral nerves are currently under investigation. The aim of the current study was to evaluate the effects of leucocyte/platelet-rich fibrin (L-PRF) with or without a collagen membrane as a supporter on crushed sciatic nerve healing in a rat model. Recovery of motor function and electrophysiologic measurements were evaluated at 4 weeks postoperatively. The whole number of myelinated axons, peripheral nerve axon density, average nerve fiber diameter (µm), and G-ratio were analyzed and compered among the groups. Functional, electrophysiological, and histological evaluations showed no significant difference among the groups with the exception of the L-PRF with collagen membrane groups that showed relatively positive effects on the functional and histological nerve recovery. In addition, the collagen membrane with L-PRF can be effect in nerve regeneration.

Kaolin-loaded chitosan/polyvinyl alcohol electrospun scaffold as a wound dressing material: in vitro and in vivo studies.

OBJECTIVE: To evaluate the application of a fabricated dressing containing kaolin for skin regeneration in a rat model of excisional wounds. METHOD: In the present study, kaolin was loaded into electrospun polyvinyl alcohol (PVA)/chitosan polymer blend to develop a composite nanofibrous dressing. To make the yarns, kaolin with weight ratio of 5% was added to PVA/chitosan polymer blend and subsequently formed into nanofibres using the electrospinning method. Scaffolds were evaluated for to their microstructure, mechanical properties, surface wettability, water vapour transmission rate, water-uptake capacity, blood uptake capacity, blood compatibility, microbial penetration test, the number of colonies, and cellular response with the L929 cell line. Rats with full-thickness excisional wounds were treated with kaolin-containing and kaolin-free dressings. RESULTS: The study showed that rats treated with the kaolin-incorporated mats demonstrated a significant closure to nearly 97.62±4.81% after 14 days compared with PVA/chitosan and the sterile gauze, which showed 86.15±8.11% and 78.50±4.22% of wound closure, respectively. The histopathological studies showed that in the PVA/chitosan/kaolin group, dense and regular collagen fibres were formed, while wounds treated with sterile gauze or PVA/chitosan scaffolds had random and loose collagen fibres. CONCLUSION: Our results show the potential applicability of PVA/chitosan/kaolin scaffolds as a wound care material.

Critical-sized bone defects regeneration using a bone-inspired 3D bilayer collagen membrane in combination with leukocyte and platelet-rich fibrin membrane (L-PRF): An in vivo study.

OBJECTIVES: We aim to develop a 3D-bilayer collagen (COL) membrane reinforced with nano beta-tricalcium-phosphate (nß-TCP) particles and to evaluate its bone regeneration in combination with leukocyte-platelet-rich fibrin (L-PRF) in vivo. BACKGROUND DATA: L-PRF has exhibited promising results as a cell carrier in bone regeneration in a number of clinical studies, however there are some studies that did not confirm the positive results of L-PRF application. METHODS: Mechanical & physiochemical characteristics of the COL/nß-TCP membrane (1/2 & 1/4) were tested. Proliferation and osteogenic differentiation of seeded cells on bilayer collagen/nß-TCP thick membrane was examined. Then, critical-sized calvarial defects in 8 white New Zealand rabbits were filled with either Col, Col/nß-TCP, Col/nß-TCP combined with L-PRF membrane, or left empty. New bone formation (NBF) was measured histomorphometrically 4 & 8 weeks postoperatively. RESULTS: Compressive modulus increases while porosity decreases with higher ß-TCP concentrations. Mechanical properties improve, with 89 % porosity (pore size ∼100 µm) in the bilayer-collagen/nß-TCP membrane. The bilayer design also enhances the proliferation and ALP activity. In vivo study shows no significant difference among test groups at 4 weeks, but Col/nß-TCP + L-PRF demonstrates more NBF compared to others (P < 0.05) after 8 weeks. CONCLUSION: The bilayer-collagen/nß-TCP thick membrane shows promising physiochemical in vitro results and significant NBF, as ¾ of the defect is filled with lamellar bone when combined with L-PRF membrane.

A collagen-based hydrogel containing tacrolimus for bone tissue engineering.

Bone tissue engineering aims to develop bone graft structure that can heal bone defects without using autografts or allografts. The current study was conducted to promote bone regeneration using a collagen type I hydrogel containing tacrolimus. For this purpose, different amounts of tacrolimus (10 µg/ml, 100 µg/ml, and 1000 µg/ml) were loaded into the hydrogel. The resulting drug-loaded hydrogels were characterized for their porosity, swelling capacity, weight loss, drug release, blood compatibility, and cell proliferation (MTT). For functional analysis, the developed hydrogel surrounded by a film made of gelatin and polycaprolactone (PCL) was administrated in the calvarias defect of Wistar rats. The results indicated that the hydrogel has a porosity of 89.2 ± 12.5% and an appropriate swelling, drug release, and blood compatibility behavior. The in vitro results indicated that the collagen hydrogel containing 1000 µg tacrolimus was adequate in terms of cell proliferation. Finally, in vivo studies provided some evidence of the potential of the developed hydrogel for bone healing.

Comparison of postoperative paresthesia after sagittal split osteotomy among different fixation methods: a one year follow-up study.

OBJECTIVES: Postoperative paresthesia is a common complication after sagittal split osteotomy (SSO). This study aimed to compare paresthesia among different fixation methods one year postoperative. MATERIALS AND METHODS: This prospective cohort study assessed subjects in four groups: class II with miniplate fixation (Group 1), class II with three-screw fixation (Group 2), class III with miniplate fixation (Group 3), and class III with three-screw fixation (Group 4). Paresthesia was evaluated one year postoperative based on a 0-10 visual analogue scale. Pearson correlation was used to evaluate associations of age and mandibular movement with paresthesia. ANOVA was used to compare paresthesia among groups. RESULTS: A total of 80 subjects were enrolled, with 20 subjects in each of the four groups. The Pearson correlation test demonstrated a significant correlation between mandibular movement and paresthesia (P=0.001). Comparison of paresthesia among the groups showed significant differences among groups 1 and 2, 2 and 3, and 3 and 4 (P<0.05). CONCLUSION: The three-screw fixation method led to more paresthesia one year postoperative compared with miniplate fixation. In addition, the magnitude of mandibular movement had a positive correlation with paresthesia.

Fabrication of Poly(L-Lactic Acid)/Chitosan Scaffolds by Solid-Liquid Phase Separation Method for Nerve Tissue Engineering: An In Vitro Study on Human Neuroblasts.

Polymeric scaffolds that support neural cell behaviors are attracting more attention. In the present study, solid-liquid phase separation technique is used to fabricate scaffolds made of poly(L-lactic acid) (PLLA) and chitosan (CS) blends to mimic both cellular microenvironment and anatomical structure of nerve tissue. The fabricated scaffolds favor characteristics of both natural and synthetic polymers. Different tests and assays including physical and mechanical ones (in vitro degradation rate, free radical release, hydrophilicity, and porosity measurements, microstructure observation, and mechanical tests) and cellular assays (cell attachment measurement and viability assessment) suggest that blend scaffolds prepared with this method support nerve cells for tissue engineering applications adequately and even better than scaffolds prepared with the same method but from pure PLLA or CS.

Fabrication and characterization of collagen-hydroxyapatite-based composite scaffolds containing doxycycline via freeze-casting method for bone tissue engineering.

In this study, hydroxyapatite nanoparticles containing 10% doxycycline, a structural isomer of tetracycline, was prepared by the co-precipitation method. It was added to collagen solution for the preparation of the scaffold with freeze-casting method in order to develop a composite scaffold with both antibacterial and osteoinductive properties for repairing bone defects. The scaffolds were evaluated regarding their morphology, porosity, degradation and cellular response. The scaffolds for further investigation were added in a rat calvaria defect model. The study showed that after eight weeks, the bone formation was relatively higher in the collagen/nano-hydroxyapatite/doxycycline group with completely filled defect when compared with other groups. Histopathological evaluation showed that the defect in the collagen/nano-hydroxyapatite/doxycycline group was fully replaced by the new bone and connective tissue. Our results provide evidence supporting the possible applicability of doxycycline-containing scaffolds for successful bone regeneration.

Mechanical, material, and biological study of a PCL/bioactive glass bone scaffold: Importance of viscoelasticity.

Microsphere sintering method was used to fabricate bone tissue engineering scaffolds made of polycaprolactone (PCL)/bioactive glass 58S5Z (58S modified with 5 wt% Zinc). First, the effect of PCL/58S5Z ratio on the mechanical properties (elastic modulus and yield strength) was investigated. It was found that samples with 5 wt% 58S5Z (named 5%BG) had the highest elastic modulus and yield strength among all samples, i.e., with 0, 5, 10, and 20 wt% bioactive glass. Then, considering the importance of viscoelastic properties of bone, the viscoelastic behavior of 0%BG (scaffold with only PCL) and 5%BG samples was determined by performing compressive stress relaxation test and subsequently a Generalized Maxwell model was developed. Findings indicated a similar amount and pattern of predicted storage and loss moduli and loss factor of the composite scaffolds to those of the bone. In the next step, the analysis of biological behavior of the scaffolds using MTT assay, DAPI and Alizarin red staining demonstrated that 5%BG scaffolds had higher in vitro cell viability and bone formation compared to 0%BG ones. Furthermore, in vivo study employing H&E staining of the scaffolds implanted in rats' calvarium for 50 days, confirmed the earlier findings and showed that 5%BG-filled defects had higher and more uniform bone formation compared to both 0%BG-filled and empty defects.

Poly(lactic-co-glycolic acid)(PLGA)/TiO2 nanotube bioactive composite as a novel scaffold for bone tissue engineering: In vitro and in vivo studies.

The aim of this study was to synthesize and characterize novel three-dimensional porous scaffolds made of poly (lactic-co-glycolic acid)/TiO2 nanotube (TNT) composite microspheres for bone tissue engineering applications. The incorporation of TNT greatly increases mechanical properties of PLGA/TNT microsphere-sintered scaffold. The experimental results exhibit that the PLGA/0.5 wt% TNT scaffold sintered at 100 °C for 3 h showed the best mechanical properties and a proper pore structure for tissue engineering. Biodegradation test ascertained that the weight of both PLGA and PLGA/PLGA/0.5 wt% TiO2 nanotube composites slightly reduced during the first 4 weeks following immersion in SBF solution. Moreover, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and alkaline phosphatase activity (ALP activity) results represent increased cell viability for PLGA/0.5%TNT composite scaffold in comparison to the control group. In vivo studies show the amount of bone formation for PLGA/TNT was approximately twice of pure PLGA. Vivid histologic images of the newly generated bone on the implants further supported our test results. Eventually, a mathematical model showed that both PLGA and PLGA/TNT scaffolds' mechanical properties follow an exponential trend with time as their degradation occurs. By a three-dimensional finite element model, a more monotonous distribution of stress was present in the scaffold due to the presence of TNT with a reduction in maximum stress on bone.

Comparative impact of systemic delivery of atorvastatin, simvastatin, and lovastatin on bone mineral density of the ovariectomized rats.

PURPOSE: In addition to lipid-lowering properties, statins have been suggested to affect bone turnover by increasing the osteoblastic bone formation and blocking the osteoclastogenesis. However, there are many controversial reports regarding the beneficial effect of statins on osteoporosis. In this study, we investigated the therapeutic effects of the most important lipophilic statins administered orally for 60 days to the ovariectomized (OVX) female Sprague-Dawley rats and compared the effects on different harvested trabecular and compact bones. METHODS: Thirty female rats were divided into five equal groups including the normal rats, untreated OVX rats (negative control), and the OVX rats treated with atorvastatin (20 mg/kg/day), simvastatin (25 mg/kg/day), and lovastatin (20 mg/kg/day). The osteoporotic animals were treated daily for 60 days and euthanized at the end of experiments. The effectiveness of these treatments was evaluated by biomechanical testing, histopathologic, histomorphometric, micro-CT scan, real-time PCR, and serum biochemical analysis. Moreover, the hepatotoxicity and rhabdomyolysis related with these treatments were assessed by biochemistry analysis and histopathological evaluation. RESULTS: The results and statistical analysis showed that systemic delivery of simvastatin and lovastatin significantly increased serum calcium level, expression of osteogenic genes, bone mineral density (BMD), and biomechanical properties in comparison to the untreated OVX rats, especially in trabecular bones (P < 0.05). The results of different analysis also indicated that there was no statistical difference between the atorvastatin-treated animals and the negative control. Among all treatments, only atorvastatin showed an evident hepatotoxicity and myopathy. CONCLUSIONS: It was concluded that the lovastatin and simvastatin efficiently ameliorated the OVX-induced osteoporosis. Moreover, the simvastatin-treated animals showed more resemblance to the normal group in terms of BMD, expression of osteogenic genes, serum biochemical parameters, histomorphometric findings, and biomechanical performance with no significant side-effects.

Can gray values derived from CT and cone beam CT estimate new bone formation? An in vivo study.

OBJECTIVES: The main aim of this study was to investigate whether Hounsfield unit derived from computed tomography (HU/CT) and gray value derived from cone beam computed tomography (GV/CBCT) can predict the amount of new bone formation (NBF) in the defects after bone reconstruction surgeries. MATERIALS AND METHODS: Thirty calvaria defects created in 5 rabbits and grafted with both radiolucent (RL, n = 15) and radiopaque (RO, n = 15) bone substitute materials were evaluated, 8 weeks postoperatively. The defects were scanned by multislice computed tomography (Somatom®, Siemens Healthineers, Erlangen, Germany) and CBCT (NewTom VG®, Qualitative Radiology, Verona, Italy). MSCT and CBCT scans were matched to select the exact region of interest (ROI, diameter = 5 mm and height = 1 mm). HU/CT and GV/CBCT of each ROI were obtained. Mean amount of NBF in whole of the defects was measured using serial histomorphometric assessment. We investigated the correlation between HU/CT and GV/CBCT, HU/CT and NBF, and GV/CBCT and NBF generally, and separately among the RL or RO grafted defects, by linear generalized estimating equation modeling. Receiver operation characteristic analysis was performed to check the accuracy of HU/CT and GV/CBCT in diagnosing more than 10% NBF in the samples. RESULTS: There were linear correlations between HU/CT and GV/CBCT, HU/CT and NBF, and GV/CBCT and NBF. CONCLUSION: According to the results, both HU/CT and GV/CBCT can be considered as fairly good predictors for assessment of the amount of NBF following bone reconstruction surgeries.

Cerium oxide nanoparticle-containing poly (ε-caprolactone)/gelatin electrospun film as a potential wound dressing material: In vitro and in vivo evaluation.

In the present study, cerium oxide (CeO2) nanoparticles were incorporated into poly (ε-caprolactone)/gelatin films in order to develop a potential wound dressing material. The wound dressings were prepared by electrospinning of poly (ε-caprolactone)/gelatin (1:1 (w/w)) solutions containing 1.50%, 3% and 6% (w/w) CeO2 nanoparticles. The electrospun films were evaluated regarding their morphology, contact angle, water-uptake capacity, water vapor transmission rate, tensile strength and cellular response. The film containing 1.50% CeO2 nanoparticles was chosen as the optimal dressing for the in vivo study on full-thickness excisional wounds of rats. The study showed that after 2weeks, the wounds treated with the CeO2 nanoparticle-containing dressing achieved a significant closure to nearly 100% compared with the sterile gauze with the nearly 63% of wound closure. Our results provided evidence supporting the possible applicability of CeO2 nanoparticle-containing wound dressing for a successful wound treatment.

Induced pluripotent stem cells as a new getaway for bone tissue engineering: A systematic review.

OBJECTIVES: Mesenchymal stem cells (MSCs) are frequently used for bone regeneration, however, they are limited in quantity. Moreover, their proliferation and differentiation capabilities reduce during cell culture expansion. Potential application of induced pluripotent stem cells (iPSCs) has been reported as a promising alternative source for bone regeneration. This study aimed to systematically review the available literature on osteogenic potential of iPSCs and to discuss methods applied to enhance their osteogenic potential. METHODS AND MATERIALS: A thorough search of MEDLINE database was performed from January 2006 to September 2016, limited to English-language articles. All in vitro and in vivo studies on application of iPSCs in bone regeneration were included. RESULTS: The current review is organized according to the PRISMA statement. Studies were categorized according to three different approaches used for osteo-induction of iPSCs. Data are summarized and reported according to the following variables: types of study, cell sources used for iPSC generation, applied reprogramming methods, applied osteo-induction methods and treatment groups. CONCLUSION: According to the articles reviewed, osteo-induced iPSCs revealed osteogenic capability equal to or superior than MSCs; cell sources do not significantly affect osteogenic potential of iPSCs; addition of resveratrol to the osteogenic medium (OM) and irradiatiation after osteogenic induction reduce teratoma formation in animal models; transfection with lentiviral bone morphogenetic protein 2 results in higher mineralization compared to osteo-induction in OM; addition of TGF-ß, IGF-1 and FGF-ß to OM increases osteogenic capability of iPSCs.