Displaying publications 61 - 80 of 145 in total

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  1. Abbas AA, Mohamad JA, Lydia AL, Selvaratnam L, Razif A, Ab-Rahim S, et al.
    JUMMEC, 2014;17(1):8-13.
    MyJurnal
    Autologous chondrocyte implantation (ACI) is a widely accepted procedure for the treatment of large, fullthickness chondral defects involving various joints, but its use in developing countries is limited because of high cost and failure rates due to limited resources and support systems. Five patients (age
  2. Subhan RA, Puvanan K, Murali MR, Raghavendran HR, Shani S, Abdullah BJ, et al.
    ScientificWorldJournal, 2014;2014:818502.
    PMID: 24983002 DOI: 10.1155/2014/818502
    This study was conducted to develop a technique for minimally invasive and accurate delivery of stem cells to augment nucleus pulposus (NP) in damaged intervertebral discs (IVD). IVD damage was created in noncontiguous discs at L4-L5 level; rabbits (N = 12) were randomly divided into three groups: group I treated with MSCs in HyStem hydrogel, group II treated with HyStem alone, and group III received no intervention. MSCs and hydrogel were administered to the damaged disc under guidance of fluoroscopy. Augmentation of NP was assessed through histological and MRI T2 mapping of the NP after eight weeks of transplantation. T2 weighted signal intensity was higher in group I than in groups II and III (P < 0.05). Disc height index showed maximum disc height in group I compared to groups II and III. Histological score of the degenerative index was significantly (P < 0.05) lower in group I (8.6 ± 1.8) than that in groups II (11.6 ± 2.3) and III (18.0 ± 5.7). Immunohistochemistry staining for collagen type II and aggrecan staining were higher in group I as compared to other groups. Our results demonstrate that the minimally invasive administration of MSCs in hyaluronan hydrogel (HyStem) augments the repair of NP in damaged IVD.
  3. Mirzamohammadi S, Aali E, Najafi R, Kamarul T, Mehrabani M, Aminzadeh A, et al.
    Cytotherapy, 2015 Jan;17(1):46-57.
    PMID: 25457279 DOI: 10.1016/j.jcyt.2014.06.009
    Mesenchymal stromal cells (MSCs) have shown great promise for cell therapy of a wide range of diseases such as diabetes. However, insufficient viability of transplanted cells reaching to damaged tissues has limited their potential therapeutic effects. Expression of estrogen receptors on stem cells may suggest a role for 17β-estradiol (E2) in regulating some functions in these cells. There is evidence that E2 enhances homing of stem cells. Induction of hypoxia-inducible factor-1α (HIF-1α) by E2 and the profound effect of HIF-1α on migration of cells have previously been demonstrated. We investigated the effect of E2 on major mediators involved in trafficking and subsequent homing of MSCs both in vitro and in vivo in diabetic rats.
  4. Barathan M, Gopal K, Mohamed R, Ellegård R, Saeidi A, Vadivelu J, et al.
    Apoptosis, 2015 Apr;20(4):466-80.
    PMID: 25577277 DOI: 10.1007/s10495-014-1084-y
    Persistent hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion to potentially assist viral persistence in the host, eventually leading to hepatocellular carcinoma. The role of HCV on the spontaneous expression of markers suggestive of immune exhaustion and spontaneous apoptosis in immune cells of chronic HCV (CHC) disease largely remain elusive. We investigated the peripheral blood mononuclear cells of CHC patients to determine the spontaneous recruitment of cellular reactive oxygen species (cROS), immunoregulatory and exhaustion markers relative to healthy controls. Using a commercial QuantiGenePlex(®) 2.0 assay, we determined the spontaneous expression profile of 80 different pro- and anti-apoptotic genes in persistent HCV disease. Onset of spontaneous apoptosis significantly correlated with the up-regulation of cROS, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2/prostaglandin H synthase (COX-2/PGHS), Foxp3, Dtx1, Blimp1, Lag3 and Cd160. Besides, spontaneous differential surface protein expression suggestive of T cell inhibition viz., TRAIL, TIM-3, PD-1 and BTLA on CD4+ and CD8+ T cells, and CTLA-4 on CD4+ T cells was also evident. Increased up-regulation of Tnf, Tp73, Casp14, Tnfrsf11b, Bik and Birc8 was observed, whereas FasLG, Fas, Ripk2, Casp3, Dapk1, Tnfrsf21, and Cflar were moderately up-regulated in HCV-infected subjects. Our observation suggests the spontaneous onset of apoptosis signaling and T cell exhaustion in chronic HCV disease.
  5. Samsudin EZ, Kamarul T, Mansor A
    Singapore Med J, 2015 May;56(5):e92-5.
    PMID: 26034328 DOI: 10.11622/smedj.2015082
    Any medical diagnosis should take a multimodal approach, especially those involving tumour-like conditions, as entities that mimic neoplasms have overlapping features and may present detrimental outcomes if they are underdiagnosed. These case reports present diagnostic pitfalls resulting from overdependence on a single diagnostic parameter for three musculoskeletal neoplasm mimics: brown tumour (BT) that was mistaken for giant cell tumour (GCT), methicillin-resistant Staphylococcus aureus osteomyelitis mistaken for osteosarcoma and a pseudoaneurysm mistaken for a soft tissue sarcoma. Literature reviews revealed five reports of BT simulating GCT, four reports of osteomyelitis mimicking osteosarcoma and five reports of a pseudoaneurysm imitating a soft tissue sarcoma. Our findings highlight the therapeutic dilemmas that arise with musculoskeletal mimics, as well as the importance of thorough investigation to distinguish mimickers from true neoplasms.
  6. Dashtdar H, Murali MR, Abbas AA, Suhaeb AM, Selvaratnam L, Tay LX, et al.
    Knee Surg Sports Traumatol Arthrosc, 2015 May;23(5):1368-1377.
    PMID: 24146054 DOI: 10.1007/s00167-013-2723-5
    PURPOSE: To investigate whether mesenchymal stem cells (MSCs) seeded in novel polyvinyl alcohol (PVA)-chitosan composite hydrogel can provide comparable or even further improve cartilage repair outcomes as compared to previously established alginate-transplanted models.

    METHODS: Medial femoral condyle defect was created in both knees of twenty-four mature New Zealand white rabbits, and the animals were divided into four groups containing six animals each. After 3 weeks, the right knees were transplanted with PVA-chitosan-MSC, PVA-chitosan scaffold alone, alginate-MSC construct or alginate alone. The left knee was kept as untreated control. Animals were killed at the end of 6 months after transplantation, and the cartilage repair was assessed through Brittberg morphological score, histological grading by O'Driscoll score and quantitative glycosaminoglycan analysis.

    RESULTS: Morphological and histological analyses showed significant (p < 0.05) tissue repair when treated with PVA-chitosan-MSC or alginate MSC as compared to the scaffold only and untreated control. In addition, safranin O staining and the glycosaminoglycan (GAG) content were significantly higher (p < 0.05) in MSC treatment groups than in scaffold-only or untreated control group. No significant difference was observed between the PVA-chitosan-MSC- and alginate-MSC-treated groups.

    CONCLUSION: PVA-chitosan hydrogel seeded with mesenchymal stem cells provides comparable treatment outcomes to that of previously established alginate-MSC construct implantation. This study supports the potential use of PVA-chitosan hydrogel seeded with MSCs for clinical use in cartilage repair such as traumatic injuries.

  7. Nam HY, Pingguan-Murphy B, Amir Abbas A, Mahmood Merican A, Kamarul T
    Biomech Model Mechanobiol, 2015 Jun;14(3):649-63.
    PMID: 25351891 DOI: 10.1007/s10237-014-0628-y
    It has been previously demonstrated that mechanical stimuli are important for multipotent human bone marrow-derived mesenchymal stromal cells (hMSCs) to maintain good tissue homeostasis and even to enhance tissue repair processes. In tendons, this is achieved by promoting the cellular proliferation and tenogenic expression/differentiation. The present study was conducted to determine the optimal loading conditions needed to achieve the best proliferation rates and tenogenic differentiation potential. The effects of mechanical uniaxial stretching using different rates and strains were performed on hMSCs cultured in vitro. hMSCs were subjected to cyclical uniaxial stretching of 4, 8 or 12 % strain at 0.5 or 1 Hz for 6, 24, 48 or 72 h. Cell proliferation was analyzed using alamarBlue[Formula: see text] assay, while hMSCs differentiation was analyzed using total collagen assay and specific tenogenic gene expression markers (type I collagen, type III collagen, decorin, tenascin-C, scleraxis and tenomodulin). Our results demonstrate that the highest cell proliferation is observed when 4 % strain [Formula: see text] 1 Hz was applied. However, at 8 % strain [Formula: see text] 1 Hz loading, collagen production and the tenogenic gene expression were highest. Increasing strain or rates thereafter did not demonstrate any significant increase in both cell proliferation and tenogenic differentiation. In conclusion, our results suggest that 4 % [Formula: see text] 1 Hz cyclic uniaxial loading increases cell proliferation, but higher strains are required for superior tenogenic expressions. This study suggests that selected loading regimes will stimulate tenogenesis of hMSCs.
  8. Hossain MM, Mukheem A, Kamarul T
    Life Sci, 2015 Aug 15;135:55-67.
    PMID: 25818192 DOI: 10.1016/j.lfs.2015.03.010
    Hypoadiponectinemia is characterized by low plasma adiponectin levels that can be caused by genetic factors, such as single nucleotide polymorphisms (SNPs) and mutations in the adiponectin gene or by visceral fat deposition/obesity. Reports have suggested that hypoadiponectinemia is associated with dyslipidemia, hypertension, hyperuricemia, metabolic syndrome, atherosclerosis, type 2 diabetes mellitus and various cardiovascular diseases. Previous studies have highlighted several potential strategies to up-regulate adiponectin secretion and function, including visceral fat reduction through diet therapy and exercise, administration of exogenous adiponectin, treatment with peroxisome proliferator-activating receptor gamma (PPARγ) agonists (e.g., thiazolidinediones (TZDs)) and ligands (e.g., bezafibrate and fenofibrate) or the blocking of the renin-angiotensin system. Likewise, the up-regulation of the expression and stimulation of adiponectin receptors by using adiponectin receptor agonists would be an effective method to treat obesity-related conditions. Notably, adiponectin is an abundantly expressed bioactive protein that also exhibits a wide spectrum of biological properties, such as insulin-sensitizing, anti-diabetic, anti-inflammatory and anti-atherosclerotic activities. Although targeting adiponectin and its receptors has been useful for treating diabetes and other metabolic-related diseases in experimental studies, current drug development based on adiponectin/adiponectin receptors for clinical applications is scarce, and there is a lack of available clinical trial data. This comprehensive review discusses the strategies that are presently being pursued to harness the potential of adiponectin up-regulation. In addition, we examined the current status of drug development and its potential for clinical applications.
  9. Fatihhi SJ, Harun MN, Abdul Kadir MR, Abdullah J, Kamarul T, Öchsner A, et al.
    Ann Biomed Eng, 2015 Oct;43(10):2487-502.
    PMID: 25828397 DOI: 10.1007/s10439-015-1305-8
    Fatigue assessment of the trabecular bone has been developed to give a better understanding of bone properties. While most fatigue studies are relying on uniaxial compressive load as the method of assessment, in various cases details are missing, or the uniaxial results are not very realistic. In this paper, the effect of three different load histories from physiological loading applied on the trabecular bone were studied in order to predict the first failure surface and the fatigue lifetime. The fatigue behaviour of the trabecular bone under uniaxial load was compared to that of multiaxial load using a finite element simulation. The plastic strain was found localized at the trabecular structure under multiaxial load. On average, applying multiaxial loads reduced more than five times the fatigue life of the trabecular bone. The results provide evidence that multiaxial loading is dominated in the low cycle fatigue in contrast to the uniaxial one. Both bone volume fraction and structural model index were best predictors of failure (p 
  10. Mehrabani M, Najafi M, Kamarul T, Mansouri K, Iranpour M, Nematollahi MH, et al.
    Cell Prolif, 2015 Oct;48(5):532-49.
    PMID: 26332145 DOI: 10.1111/cpr.12209
    OBJECTIVES: Both excessive and insufficient angiogenesis are associated with progression of diabetic complications, of which poor angiogenesis is an important feature. Currently, adipose-derived stem cells (ADSCs) are considered to be a promising source to aid therapeutic neovascularization. However, functionality of these cells is impaired by diabetes which can result from a defect in hypoxia-inducible factor-1 (HIF-1), a key mediator involved in neovascularization. In the current study, we sought to explore effectiveness of pharmacological priming with deferoxamine (DFO) as a hypoxia mimetic agent, to restore the compromised angiogenic pathway, with the aid of ADSCs derived from streptozotocin (STZ)-induced type 1 diabetic rats ('diabetic ADSCs').

    MATERIALS AND METHODS: Diabetic ADSCs were treated with DFO and compared to normal and non-treated diabetic ADSCs for expression of HIF-1α, VEGF, FGF-2 and SDF-1, at mRNA and protein levels, using qRT-PCR, western blotting and ELISA assay. Activity of matrix metalloproteinases -2 and -9 were measured using a gelatin zymography assay. Angiogenic potential of conditioned media derived from normal, DFO-treated and non-treated diabetic ADSCs were determined by in vitro (in HUVECs) and in vivo experiments including scratch assay, three-dimensional tube formation testing and surgical wound healing models.

    RESULTS: DFO remarkably enhanced expression of noted genes by mRNA and protein levels and restored activity of matrix metalloproteinases -2 and -9. Compromised angiogenic potential of conditioned medium derived from diabetic ADSCs was restored by DFO both in vitro and in vivo experiments.

    CONCLUSION: DFO preconditioning restored neovascularization potential of ADSCs derived from diabetic rats by affecting the HIF-1α pathway.

  11. Puvaneswary S, Talebian S, Raghavendran HB, Murali MR, Mehrali M, Afifi AM, et al.
    Carbohydr Polym, 2015 Dec 10;134:799-807.
    PMID: 26428187 DOI: 10.1016/j.carbpol.2015.07.098
    We developed tricalcium phosphate-chitosan-fucoidan biocomposite scaffold (TCP-Ch-Fu) by using the freeze-drying technique. The fabricated biocomposite scaffolds were analyzed by spectroscopy and porosity measurement. The biomechanical properties of scaffolds were assessed by compression test and the results suggested that the incorporation of Fucoidan into the biocomposite improves the compression strength of scaffolds. Biomineralization of scaffolds was evaluated by soaking them in simulated body fluid and the results revealed that the addition of Fucoidan into the scaffolds enhanced the formation of apatite layer on the surface of biocomposite after 7 days of immersion. Alamar Blue assay confirmed that the cell viability of human-derived bone marrow stromal cell was superior in the TCP-Ch-Fuscaffold. The addition of Fucoidan to TCP-Ch increased the release of osteocalcin, confirming that it can support osteogenic differentiation of human mesenchymal stromal cells in in vitro culture. Thus, TCP-Ch-Fu could be a potential candidate for bone-tissue engineering applications.
  12. Gopal K, Gowtham M, Sachin S, Ravishankar Ram M, Shankar EM, Kamarul T
    Sci Rep, 2015 Dec 16;5:18300.
    PMID: 26670291 DOI: 10.1038/srep18300
    Angiotensin II is one of the key regulatory peptides implicated in the pathogenesis of liver disease. The mechanisms underlying the salubrious role of α-tocopherol and β-carotene on liver pathology have not been comprehensively assessed. Here, we investigated the mechanisms underlying the role of Angiotensin II on hepatic damage and if α-tocopherol and β-carotene supplementation attenuates hepatic damage. Hepatic damage was induced in Apoe(-/-)mice by infusion of Angiotensin II followed by oral administration with α-tocopherol and β-carotene-enriched diet for 60 days. Investigations showed fibrosis, kupffer cell hyperplasia, hepatocyte degeneration and hepatic cell apoptosis; sinusoidal dilatation along with haemorrhages; evidence of fluid accumulation; increased ROS level and increased AST and ALT activities. In addition, tPA and uPA were down-regulated due to 42-fold up-regulation of PAI-1. MMP-2, MMP-9, MMP-12, and M-CSF were down-regulated in Angiotensin II-treated animals. Notably, α-tocopherol and β-carotene treatment controlled ROS, fibrosis, hepatocyte degeneration, kupffer cell hyperplasia, hepatocyte apoptosis, sinusoidal dilatation and fluid accumulation in the liver sinusoids, and liver enzyme levels. In addition, PAI-1, tPA and uPA expressions were markedly controlled by β-carotene treatment. Thus, Angiotensin II markedly influenced hepatic damage possibly by restraining fibrinolytic system. We concluded that α-tocopherol and β-carotene treatment has salubrious role in repairing hepatic pathology.
  13. Tan SL, Ahmad TS, Ng WM, Azlina AA, Azhar MM, Selvaratnam L, et al.
    PLoS One, 2015;10(11):e0140869.
    PMID: 26528540 DOI: 10.1371/journal.pone.0140869
    To date, the molecular signalling mechanisms which regulate growth factors-induced MSCs tenogenic differentiation remain largely unknown. Therefore, a study to determine the global gene expression profile of tenogenic differentiation in human bone marrow stromal cells (hMSCs) using growth differentiation factor 5 (GDF5) was conducted. Microarray analyses were conducted on hMSCs cultures supplemented with 100 ng/ml of GDF5 and compared to undifferentiated hMSCs and adult tenocytes. Results of QuantiGene® Plex assay support the use and interpretation of the inferred gene expression profiles and pathways information. From the 27,216 genes assessed, 873 genes (3.21% of the overall human transcriptome) were significantly altered during the tenogenic differentiation process (corrected p<0.05). The genes identified as potentially associated with tenogenic differentiation were ARHGAP29, CCL2, integrin alpha 8 and neurofilament medium polypeptides. These genes, were mainly associated with cytoskeleton reorganization (stress fibers formation) signaling. Pathway analysis demonstrated the potential molecular pathways involved in tenogenic differentiation were: cytoskeleton reorganization related i.e. keratin filament signaling and activin A signaling; cell adhesion related i.e. chemokine and adhesion signaling; and extracellular matrix related i.e. arachidonic acid production signaling. Further investigation using atomic force microscopy and confocal laser scanning microscopy demonstrated apparent cytoskeleton reorganization in GDF5-induced hMSCs suggesting that cytoskeleton reorganization signaling is an important event involved in tenogenic differentiation. Besides, a reduced nucleostemin expression observed suggested a lower cell proliferation rate in hMSCs undergoing tenogenic differentiation. Understanding and elucidating the tenogenic differentiation signalling pathways are important for future optimization of tenogenic hMSCs for functional tendon cell-based therapy and tissue engineering.
  14. Krishnamurithy G, Murali MR, Hamdi M, Abbas AA, Raghavendran HB, Kamarul T
    Regen Med, 2015;10(5):579-90.
    PMID: 26237702 DOI: 10.2217/rme.15.27
    To compare the effect of bovine bone derived porous hydroxyapatite (BDHA) scaffold on proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hMSCs) compared with commercial hydroxyapatite (CHA) scaffold.
  15. Almasi D, Izman S, Sadeghi M, Iqbal N, Roozbahani F, Krishnamurithy G, et al.
    Int J Biomater, 2015;2015:475435.
    PMID: 25838826 DOI: 10.1155/2015/475435
    Polyether ether ketone (PEEK) is considered the best alternative material for titanium for spinal fusion cage implants due to its low elasticity modulus and radiolucent property. The main problem of PEEK is its bioinert properties. Coating with hydroxyapatite (HA) showed very good improvement in bioactivity of the PEEK implants. However the existing methods for deposition of HA have some disadvantages and damage the PEEK substrate. In our previous study a new method for deposition of HA on PEEK was presented. In this study cell proliferation of mesenchymal stem cell and apatite formation in simulated body fluid (SBF) tests were conducted to probe the effect of this new method in improvement of the bioactivity of PEEK. The mesenchymal stem cell proliferation result showed better cells proliferation on the treated layer in comparison with untreated PEEK. The apatite formation results showed the growth of the HA on the treated PEEK but there was not any sight of the growth of HA on the untreated PEEK even after 2 weeks. The results showed the new method of the HA deposition improved the bioactivity of the treated PEEK in comparison with the bare PEEK.
  16. Moradi A, Ataollahi F, Sayar K, Pramanik S, Chong PP, Khalil AA, et al.
    J Biomed Mater Res A, 2016 Jan;104(1):245-56.
    PMID: 26362913 DOI: 10.1002/jbm.a.35561
    Extracellular matrices have drawn attention in tissue engineering as potential biomaterials for scaffold fabrication because of their bioactive components. Noninvasive techniques of scaffold fabrication and cross-linking treatments are believed to maintain the integrity of bioactive molecules while providing proper architectural and mechanical properties. Cartilage matrix derived scaffolds are designed to support the maintenance of chondrocytes and provide proper signals for differentiation of chondroinducible cells. Chondroinductive potential of bovine articular cartilage matrix derived porous scaffolds on human dermal fibroblasts and the effect of scaffold shrinkage on chondrogenesis were investigated. An increase in sulfated glycosaminoglycans production along with upregulation of chondrogenic genes confirmed that physically treated cartilage matrix derived scaffolds have chondrogenic potential on human dermal fibroblasts.
  17. Pourshahrestani S, Zeimaran E, Adib Kadri N, Gargiulo N, Samuel S, Naveen SV, et al.
    J Mater Chem B, 2016 Jan 07;4(1):71-86.
    PMID: 32262810 DOI: 10.1039/c5tb02062j
    Haemorrhage remains the leading cause of potentially survivable death in both military and civilian populations. Although a large variety of hemostatic agents have been developed, many of them have an inadequate capacity to induce hemostasis and are not effective in killing bacteria. In recent years, mesoporous bioactive glasses (MBGs) were found to be effective in inducing hemostasis. However, the materials may not be considered as ideal hemostats since they do not offer antimicrobial activity. The gallium ion (Ga+3) not only exhibits antibacterial properties but also accelerates the blood coagulation cascade. The aim of this study was to develop MBGs containing various concentrations of Ga2O3 (1, 2 & 3 mol%) via the evaporation-induced self-assembly (EISA) process and investigate whether the addition of Ga3+ would induce both hemostatic and antibacterial effects. The results indicated that the incorporation of lower Ga2O3 content (1 mol%) into the MBG system improved structural properties including the specific surface area, mesopore size and pore volume as well as the release of silicon and calcium ions. The bioactive glass was found to stimulate blood coagulation, platelet adhesion and thrombus generation and exerted an antibacterial effect against both Escherichia coli and Staphylococcus aureus. Likewise, Ga-doped MBGs showed excellent cytocompatibility even after 3 days, with the 1% Ga2O3-containing MBG attaining the best biocompatibility that render them safe hemostatic agents for stopping bleeding. This study demonstrated that the lowest Ga2O3-substituted MBG can be a potent candidate for controlling haemorrhage and wound infection.
  18. Fatihhi SJ, Rabiatul AA, Harun MN, Kadir MR, Kamarul T, Syahrom A
    J Mech Behav Biomed Mater, 2016 Feb;54:21-32.
    PMID: 26410762 DOI: 10.1016/j.jmbbm.2015.09.006
    The present study reports the effects of combined torsional and compressive cyclic loading on trabecular bone in order to mimic true physiological conditions and thereby provides improved data that represents clinical and real life conditions. However, only compressive behaviour is evaluated in most previous studies of bone mechanics. From the monotonic evaluation, it is observed that lower stress is needed for the onset of microcrack in the sample under torsional loading, compared to the stress needed in compression. Trabecular bone samples were subjected to a combination of torsion and compression fatigue at different stress levels during which they were compared to compressive axial fatigue. The stress levels were determined by considering the monotonic strength at 25-50% for both compressive and shear stresses. Significant decrease in fatigue lifetime is observed in between samples of pure compression fatigue and those with superpositioned torsional loading (p<0.05). The reduction in fatigue lifetime became more evident at a high torsional stress level. In this case, the failure of the sample is said to be 'torsional dominant'. Fatigue behaviour of bovine trabecular bone begins with plastic deformation, followed by strain accumulation and modulus reduction. As the strain rate increases, more energy dissipates and the sample finally failed. Further, the analysis of fractograph revealed something on the trabeculae by bending in sample with superpositioned torsional loading. In conclusion, torsional loading decreases the quality of the trabecular properties in terms of stiffness, life and structural integrity. It is hoped that results from this study will improve the understanding of the behaviour of trabecular bone under combined fatigue and help to develop future assessments of trabecular failure.
  19. Raghavendran HR, Mohan S, Genasan K, Murali MR, Naveen SV, Talebian S, et al.
    Colloids Surf B Biointerfaces, 2016 Mar 1;139:68-78.
    PMID: 26700235 DOI: 10.1016/j.colsurfb.2015.11.053
    Scaffolds with structural features similar to the extracellular matrix stimulate rapid osteogenic differentiation in favorable microenvironment and with growth factor supplementation. In this study, the osteogenic potential of electrospun poly-l-lactide/hydroxyapatite/collagen (PLLA/Col/HA, PLLA/HA and PLLA/Col) scaffolds were tested in vitro with the supplementation of platelet derived growth factor-BB (PDGF-BB). Cell attachment and topography, mineralization, extracellular matrix protein localization, and gene expression of the human mesenchymal stromal cells were compared between the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA. The levels of osteocalcin, calcium, and mineralization were significantly greater in the PLLA/Col/HA and PLLA/HA compared with PLLA/Col. High expression of fibronectin, intracellular adhesion molecule, cadherin, and collagen 1 (Col1) suggests that PLLA/Col/HA and PLLA/HA scaffolds had superior osteoinductivity than PLLA/Col. Additionally, osteopontin, osteocalcin, osterix, Runt-related transcription factor 2 (Runx2), and bone morphogenic protein (BMP2) expression were higher in PLLA/Col/HA and PLLA/HA compared with PLLA/Col. In comparison with PLLA/Col, the PLLA/Col/HA and PLLA/HA scaffolds presented a significant upregulation of the genes Runx2, Col 1, Integrin, osteonectin (ON), bone gamma-carboxyglutamic acid-containing protein (BGALP), osteopontin (OPN), and BMP2. The upregulation of these genes was further increased with PDGF-BB supplementation. These results show that PDGF-BB acts synergistically with PLLA/Col/HA and PLLA/HA to enhance the osteogenic differentiation potential. Therefore, this combination can be used for the rapid expansion of bone marrow stromal cells into bone-forming cells for tissue engineering.
  20. Ibrahim MR, Singh S, Merican AM, Raghavendran HR, Murali MR, Naveen SV, et al.
    BMC Vet Res, 2016 Jun 16;12(1):112.
    PMID: 27307015 DOI: 10.1186/s12917-016-0724-6
    Fracture healing in bone gap is one of the major challenges encountered in Orthopedic Surgery. At present, the treatment includes bone graft, employing either internal or external fixation which has a significant impact on the patient, family and even society. New drugs are emerging in the markets such as anabolic bone-forming agents including teriparatide and strontium ranelate to stimulate bone growth. Based on the mechanism of their actions, we embarked on a study on the healing of a fractured ulna with bone gap in a rabbit model. We segregated ten rabbits into two groups: five rabbits in the test group and five rabbits in the control group. We created a 5 mm bone gap in the ulna bone, removing the periosteum as well. Rabbits in the test group received 450 mg/kg of strontium ranelate via oral administration, daily, for six weeks. The x-rays, CT scans and blood tests were performed every two weeks. At the end of six weeks, the rabbits were sacrificed, and the radius and ulna bones harvested for histopathological examination.
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