Sangeetha Naveen | University of Malaya, Malaysia (original) (raw)

Papers by Sangeetha Naveen

Geometric variable designs of cam/post mechanisms influence the kinematics of knee implants

Materials Letters, 2017

Bovine hydroxyapatite, a widely used scaffold in tissue engineering, is sintered at varied temper... more Bovine hydroxyapatite, a widely used scaffold in tissue engineering, is sintered at varied temperatures (600ºC, 700ºC, 750ºC, 800ºC, 900ºC and 1000ºC) and was evaluated for its osseo-integration potential with human bone marrow derived mesenchymal stromal cells. The cell attachment, distribution, morphology, and osteogenic marker assays were analysed. SEM analysis on day 11 revealed the porous structure and well-defined equiaxed HAp grain morphology and its affinity for cell attachment. While confocal microscopy showed viable cells on all samples, the proliferation assay indicated that cells in monolayer is significantly higher on day 11 and 15 than the scaffold (p<0.05). Significant differences were observed only between certain groups (750:600 and 750:1000) at day 11, however, no difference was observed between the groups after day 15. Osteogenic marker assays revealed that the bovine scaffold sintered at 750ºC exhibited superior osteoinductivity than others. These findings indicate that the bovine HAp sintered at 750ºC may act as a potential biomaterial for possible tissue engineering applications.

PeerJ, 2016

Previous studies have shown that platelet concentrates used in conjunction with appropriate growt... more Previous studies have shown that platelet concentrates used in conjunction with appropriate growth media enhance osteogenic differentiation of human mesenchymal stromal cells (hMSCs). However, their potential in inducing osteogenesis of hMSCs when cultured in serum free medium has not been explored. Furthermore, the resulting osteogenic molecular signatures of the hMSCs have not been compared to standard osteogenic medium. We studied the effect of infrequent supplementation (8-day interval) of 15% non-activated platelet-rich concentrate (PRC) in serum free medium on hMSCs proliferation and differentiation throughout a course of 24 days, and compared the effect with those cultured in a standard osteogenic medium (OM). Cell proliferation was analyzed by alamar blue assay. Gene expression of osteogenic markers (Runx2, Collagen1, Alkaline Phosphatase, Bone morphogenetic protein 2, Osteopontin, Osteocalcin, Osteonectin) were analyzed using Q-PCR. Immunocytochemical staining for osteocalc...

$Research paper thumbnail of The effect of strontium ranelate on the healing of a fractured ulna with bone gap in rabbit$

BMC veterinary research, Jan 16, 2016

Fracture healing in bone gap is one of the major challenges encountered in Orthopedic Surgery. At... more 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...

Colloids and Surfaces B: Biointerfaces, 2016

Scaffolds with structural features similar to the extracellular matrix stimulate rapid osteogenic... more 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.

Journal of Materials Chemistry B, 2016

Gallium-containing mesoporous bioactive glass can be considered as an efficient hemostatic materi... more Gallium-containing mesoporous bioactive glass can be considered as an efficient hemostatic material due to its merits of increased platelet adhesion and thrombin formation as well as antibacterial properties.

Journal of Non-Crystalline Solids, 2015

Bioactive glasses represent a class of attractive materials in bone reconstruction. This study de... more Bioactive glasses represent a class of attractive materials in bone reconstruction. This study describes the detailed preparation and characterization of a silicate-based bioactive glass-ceramic (R-SBgC). Synthesis of bioactive glasses using the sol-gel method has advantages compared to the melting method. However, expensive raw materials are required and pose a major issue. To overcome this, R-SBgC was synthesized via the sol-gel method using Rice Husk (RH) as a natural silica precursor. The RH was heat treated and used as an alternative to tetraethyl orthosilicate (TEOS), which is a common synthetic silica precursor. X-ray diffraction (XRD), X-ray Fluorescence (XRF) and Scanning Electron Microscopy (SEM) were used to characterize the rice husk ash (RHA). The findings reveal that the extracted silica has a high purity (~99%). The synthesized R-SBgC powder was characterized using SEM, Energy Dispersive X-ray Analysis (EDX), XRD, XRF and Fourier-Transform Infrared Spectroscopy (FTIR) to complete the morphological and elemental analysis. Moreover, in vitro bioactivity via an immersion assessment was conducted for up to 14 days. The HA layer formation, which is an indicator of the bioactivity on the surface of the R-SBgC, was confirmed using SEM, EDX and further by FTIR. Biocompatibility of the R-SBgC was evaluated in vitro. After 3 days of human bone marrow stromal cell (hBMSC) seeding, SEM analysis revealed cell attachment on the surface of the R-SBgC. Alamar blue and XTT cytotoxic assays demonstrated cell proliferation abilities and the non-cytotoxic effect of the R-SBgC. Altogether, the results demonstrate that prepared rice husk-derived bioactive glass ceramic may be a promising carrier for tissue engineering applications.

Indian journal of experimental biology, 2012

Despite being a complex degenerative joint disease, studies on osteoarthritis (OA) suggest that i... more Despite being a complex degenerative joint disease, studies on osteoarthritis (OA) suggest that its progression can be reduced by the use of hyaluronic acid (HA) or mesenchymal stem cells (MSC). The present study thus aims to examine the effects of MSC, HA and the combination of HA-MSC in treating OA in rat model. The histological observations using O'Driscoll score indicate that it is the use of HA and MSC independently and not their combination that delays the progression of OA. In conclusion, the preliminary study suggest that the use of either HA or MSCs effectively reduces OA progression better than their combined use.

Knee Surgery, Sports Traumatology, Arthroscopy, 2014

straight post showed 16.1 and 15.8 mm femoral rollback, respectively. Conclusion The present stud... more straight post showed 16.1 and 15.8 mm femoral rollback, respectively. Conclusion The present study demonstrates that the use of circle cam and convex post created the best femoral rollback effect which in turn produces the highest amount of knee flexion. The findings of the study suggest that if the design is applied for knee implants, superior knee flexion may be possible for future patients. Level of evidence IV.

Materials Letters, 2015

In the present study, we developed an unmodified/raw Medium chain length-PHA (MCL-PHA) polyhydrox... more In the present study, we developed an unmodified/raw Medium chain length-PHA (MCL-PHA) polyhydroxyalkanoate (PHA), natural microbial polyester by using cost-effective saponified palm kernel oil (SPKO) technique. The functional groups, elemental composition, phase purity, water contact angle, and in vitro human-derived mesenchymal stromal cell attachment were examined. FTIR confirmed the presence of functional groups corresponding to alkyl halide, alkyne, hydroxyl group, and alkane groups, while XRD and EDX results revealed its phase purity and presence of elements such as carbon and oxygen respectively. SEM and confocal microscope analyses revealed that the bio-material supports cell attachment and this was further confirmed through cell viability assay. In conclusion, the characterization and compatibility studies revealed that this novel scaffold could be a potential candidate for possible tissue engineering applications.

Integrative Medicine Research, 2014

Helicobacter pylori, a spiral-shaped Gram-negative bacterium, has been classified as a class I ca... more Helicobacter pylori, a spiral-shaped Gram-negative bacterium, has been classified as a class I carcinogen by the World Health Organization and recognized as the causative agent for peptic ulcers, duodenal ulcer, gastritis, mucosa-associated lymphoid tissue lymphomas, and gastric cancer. Owing to their alarming rate of drug resistance, eradication of H. pylori remains a global challenge. Triple therapy consisting of a proton pump inhibitor, clarithromycin, and either amoxicillin or metronidazole, is generally the recommended standard for the treatment of H. pylori infection. Complementary and alternative medicines have a long history in the treatment of gastrointestinal ailments and various compounds has been tested for anti-H. pylori activity both in vitro and in vivo; however, their successful use in human clinical trials is sporadic. Hence, the aim of this review is to analyze the role of some well-known natural products that have been tested in clinical trials in preventing, altering, or treating H. pylori infections. Whereas some in vitro and in vivo studies in the literature have demonstrated the successful use of a few potential natural products for the treatment of H. pylori-related infections, others indicate a need to consider natural products, with or without triple therapy, as a useful alternative in treating H. pylori-related infections. Thus, the reported mechanisms include killing of H. pylori urease inhibition, induction of bacterial cell damage, and immunomodulatory effect on the host immune system. Furthermore, both in vitro and in vivo studies have demonstrated the successful use of some potential natural products for the treatment of H. pylori-related infections. Nevertheless, the routine prescription of potential complementary and alternative medicines continues to be restrained, and evidence on the safety and efficacy of the active compounds remains a subject of ongoing debate.

BMC Veterinary Research, 2013

Background In many pre-clinical studies of cartilage tissue, it has been generally assumed that t... more Background In many pre-clinical studies of cartilage tissue, it has been generally assumed that the major difference of the tissue between the species is the tissue thickness, which is related to the size of the animal itself. At present, there appear to be lack of studies demonstrating the relationship between chondrocyte densities, protein content, gene expressions and cartilage thickness in the various animal models that are commonly used. The present study was conducted to determine whether or not chondrocyte density, proteoglycan/protein content and selective chondrocyte gene expression are merely related to the cartilage thickness (thus animal size), and not the intrinsic nature of the species being investigated. Mature animals (rabbit, rats and goats) were sacrificed for their hind knee cartilages. Image analyses were performed on five consecutive histological sections, sampled from three pre-defined locations at the lateral and medial femoral condyles. Cartilage thickness, c...

Arthritis Research & Therapy, 2013

Introduction: Treatment of chondral injuries remains a major issue despite the many advances made... more Introduction: Treatment of chondral injuries remains a major issue despite the many advances made in cartilage repair techniques. Although it has been postulated that the use of marrow stimulation in combination with cell-based therapy may provide superior outcome, this has yet to be demonstrated. A pilot study was thus conducted to determine if bone marrow derived mesenchymal stromal cells (BM-MSCs) have modulatory effects on the repair outcomes of bone marrow stimulation (BMS) techniques. Methods: Two full-thickness chondral 5 mm diameter defects were created in tandem on the medial condyle of left stifle joints of 18 Boer caprine (N = 18). Goats were then divided equally into three groups. Simultaneously, bone marrow aspirates were taken from the iliac crests from the goats in Group 1 and were sent for BM-MSC isolation and expansion in vitro. Six weeks later, BMS surgery, which involves subchondral drilling at the defect sites, was performed. After two weeks, the knees in Group 1 were given autologous intra-articular BM-MSCs (N = 6). In Group 2, although BMS was performed there were no supplementations provided. In Group 3, no intervention was administered. The caprines were sacrificed after six months. Repairs were evaluated using macroscopic assessment through the International Cartilage Repair Society (ICRS) scoring, histologic grading by O'Driscoll score, biochemical assays for glycosaminoglycans (GAGs) and gene expressions for aggrecan, collagen II and Sox9. Results: Histological and immunohistochemical analyses demonstrated hyaline-like cartilage regeneration in the transplanted sites particularly in Group 1. In contrast, tissues in Groups 2 and 3 demonstrated mainly fibrocartilage. The highest ICRS and O'Driscoll scorings was also observed in Group 1, while the lowest score was seen in Group 3. Similarly, the total GAG/total protein as well as chondrogenic gene levels were expressed in the same order, that is highest in Group 1 while the lowest in Group three. Significant differences between these 3 groups were observed (P <0.05). Conclusions: This study suggests that supplementing intra-articular injections of BM-MSCs following BMS knee surgery provides superior cartilage repair outcomes.

International Journal of Medical Sciences, 2014

Monosodium-iodoacetate (MIA)-induced animal model of osteoarthritis (OA) is under-utilised despit... more Monosodium-iodoacetate (MIA)-induced animal model of osteoarthritis (OA) is under-utilised despite having many inherent advantages. At present, there is lack of studies that directly compare the degenerative changes induced by MIA with the surgical osteoarthritis induction method and human osteoarthritis, which would further verify a greater use of this model. Therefore, we compared the histological, biochemical and biomechanical characteristics in rat model using MIA against the anterior cruciate ligament transection (ACLT) and human cartilage with clinically established osteoarthritis. The right knees of Sprague-Dawley rats were subjected to either MIA or ACLT (n=18 in each group). Six rats were used as controls. Human cartilage samples were collected and compared from patients clinically diagnosed with (n=7) and without osteoarthritis (n=3). Histological, biochemical (Glycosaminoglycans/total protein) and biomechanical (cartilage stiffness) evaluations were performed at the end of the 1 st and 2 nd week after OA induction. For human samples, evaluations were performed at the time of sampling. Histopathological changes in the MIA group were comparable to that observed in the ACLT group and human OA. The Mankin scores of the 3 groups were comparable (MIA: 11.5±1.0; ACLT: 10.1±1.1; human OA: 13.2±0.8). Comparable reduction in Glycosaminoglycan/total protein content in the intervention groups were observed (MIA: 7±0.6; ACLT: 6.6±0.5; human OA: 3.1±0.7). Cartilage stiffness score were 24.2±15.3 Mpa for MIA, 25.3±4.8 for ACLT and 0.5±0.0 Mpa for human OA. The MIA model produces comparable degenerative changes to ACLT and human OA with the advantage of being rapid, minimally invasive and reproducible. Therefore, wider utilisation of MIA as animal translational OA model should perhaps be advocated.

PLoS ONE, 2014

A comparative study on the in vitro osteogenic potential of electrospun poly-L-lactide/hydroxyapa... more A comparative study on the in vitro osteogenic potential of electrospun poly-L-lactide/hydroxyapatite/collagen (PLLA/HA/ Col, PLLA/HA, and PLLA/Col) scaffolds was conducted. The morphology, chemical composition, and surface roughness of the fibrous scaffolds were examined. Furthermore, cell attachment, distribution, morphology, mineralization, extracellular matrix protein localization, and gene expression of human mesenchymal stromal cells (hMSCs) differentiated on the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA were also analyzed. The electrospun scaffolds with a diameter of 200-950 nm demonstrated well-formed interconnected fibrous network structure, which supported the growth of hMSCs. When compared with PLLA/H%A and PLLA/Col scaffolds, PLLA/Col/HA scaffolds presented a higher density of viable cells and significant upregulation of genes associated with osteogenic lineage, which were achieved without the use of specific medium or growth factors. These results were supported by the elevated levels of calcium, osteocalcin, and mineralization (P,0.05) observed at different time points (0, 7, 14, and 21 days). Furthermore, electron microscopic observations and fibronectin localization revealed that PLLA/Col/HA scaffolds exhibited superior osteoinductivity, when compared with PLLA/ Col or PLLA/HA scaffolds. These findings indicated that the fibrous structure and synergistic action of Col and nano-HA with high-molecular-weight PLLA played a vital role in inducing osteogenic differentiation of hMSCs. The data obtained in this study demonstrated that the developed fibrous PLLA/Col/HA biocomposite scaffold may be supportive for stem cell based therapies for bone repair, when compared with the other two scaffolds.

Macromolecular Bioscience

Stem Cells International

We have determined the protective effects of Thymus serpyllum (TS) extract and nanoparticle-loade... more We have determined the protective effects of Thymus serpyllum (TS) extract and nanoparticle-loaded TS on hydrogen peroxide-induced cell death of mesenchymal stromal cells (MSCs) in vitro. Gas chromatography–mass spectroscopy confirmed the spectrum of active components in the extract. Out of the three different extracts, the hexane extract showed significant free radical scavenging activity. Treatment of MSCs with H2O2 (hydrogen peroxide) significantly increased intracellular cell death; however, pretreatment with TS extract and nanoparticle-loaded TS (200 μg/ml) suppressed H2O2-induced elevation of Cyt-c and MMP13 and increased the survival rates of MSCs. H2O2-induced (0.1 mM) changes in cytokines were attenuated in the extract and nanoparticles by pretreatment and cotreatment at two time points (p<0.05). H2O2 increased cell apoptosis. In contrast, treatment with nanoparticle-loaded TS suppressed the percentage of apoptosis considerably (p<0.05). Therefore, TS may be considere...

Materials Science and Engineering: C

A novel series of silver-doped mesoporous bioactive glass/poly(1,8-octanediol citrate) (AgMBG/POC... more A novel series of silver-doped mesoporous bioactive glass/poly(1,8-octanediol citrate) (AgMBG/POC) elastomeric biocomposite scaffolds were successfully constructed by a salt-leaching technique for the first time and the effect of inclusion of different AgMBG contents (5, 10, and 20 wt%) on physicochemical and biological properties of pure POC elastomer was evaluated. Results indicated that AgMBG particles were uniformly dispersed in the POC matrix and increasing the AgMBG concentration into POC matrix up to 20 wt% enhanced thermal behaviour, mechanical properties and water uptake ability of the composite scaffolds compared to those from POC. The 20%AgMBG/POC additionally showed higher degradation rate in Tris(hydroxymethyl)-aminomethane–HCl (Tris–HCl) compared with pure POC and lost about 26% of its initial weight after soaking for 28 days. The AgMBG phase incorporation also significantly endowed the resulting composite scaffolds with efficient antibacterial properties against Escherichia coli and Staphylococcus aureus bacteria while preserving their favorable biocompatibility with soft tissue cells (i.e., human dermal fibroblast cells). Taken together, our results suggest that the synergistic effect of both AgMBG and POC make these newly designed AgMBG/POC composite scaffold an attractive candidate for soft tissue engineering applications.

Toxicology Research

Cerium oxide nanoparticles showed negligible local effects, low systemic toxicity and genotoxicit... more Cerium oxide nanoparticles showed negligible local effects, low systemic toxicity and genotoxicity via implantation route.