Simon McKenzie Cool
Email Address
dossmc@nus.edu.sg
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Publication Complexation and Sequestration of BMP-2 from an ECM Mimetic Hyaluronan Gel for Improved Bone Formation(2013) Kisiel M.; Klar A.S.; Ventura M.; Buijs J.; Mafina M.-K.; Cool S.M.; Hilborn J.; ORTHOPAEDIC SURGERYBone morphogenetic protein-2 (BMP-2) is considered a promising adjuvant for the treatment of skeletal non-union and spinal fusion. However, BMP-2 delivery in a conventional collagen scaffold necessitates a high dose to achieve an efficacious outcome. To lower its effective dose, we precomplexed BMP-2 with the glycosaminoglycans (GAGs) dermatan sulfate (DS) or heparin (HP), prior to loading it into a hyaluronic acid (HA) hydrogel. In vitro release studies showed that BMP-2 precomplexed with DS or HP had a prolonged delivery compared to without GAG. BMP-2-DS complexes achieved a slightly faster release in the first 24 h than HP; however, both delivered BMP-2 for an equal duration. Analysis of the kinetic interaction between BMP-2 and DS or HP showed that HP had approximately 10 times higher affinity for BMP-2 than DS, yet it equally stabilized the protein, as determined by alkaline phosphatase activity. Ectopic bone formation assays at subcutaneous sites in rats demonstrated that HA hydrogel-delivered BMP-2 precomplexed with GAG induced twice the volume of bone compared with BMP-2 delivered uncomplexed to GAG. © 2013 Kisiel et al.Publication Glycosaminoglycan composition changes with MG-63 osteosarcoma osteogenesis in vitro and induces human mesenchymal stem cell aggregation(2009) Kumarasuriyar, A.; Murali, S.; Nurcombe, V.; Cool, S.M.; ORTHOPAEDIC SURGERYPublication De-sulfation of MG-63 cell glycosaminoglycans delays in vitro osteogenesis, up-regulates cholesterol synthesis and disrupts cell cycle and the actin cytoskeleton(2009) Kumarasuriyar, A.; Lee, I.; Nurcombe, V.; Cool, S.M.; ORTHOPAEDIC SURGERYPublication A novel use of TAT-EGFP to validate techniques to alter osteosarcoma cell surface glycosaminoglycan expression(2007) Kumarasuriyar, A.; Dombrowski, C.; Rider, D.A.; Nurcombe, V.; Cool, S.M.; ORTHOPAEDIC SURGERYPublication Porcine bone marrow stromal cell differentiation on heparin-adsorbed poly(e-caprolactone)-tricalcium phosphate-collagen scaffolds(2009-11) Chum, Z.Z.; Woodruff, M.A.; Cool, S.M.; Hutmacher, D.W.; ORTHOPAEDIC SURGERYWe evaluate the potential of heparin as a substrate component for the fabrication of bone tissue engineering constructs using poly(e-caprolactone)-tricalcium phosphate-collagen type I (PCL-TCP-Col) three-dimensional (3-D) scaffolds. First we explored the ability of porcine bone marrow precursor cells (MPCs) to differentiate down both the adipogenic and osteogenic pathways within 2-D culture systems, with positive results confirmed by Oil-Red-O and Alizarin Red staining, respectively. Secondly, we examined the influence of heparin on the interaction and behaviour of MPCs when seeded onto PCL-TCP-Col 3-D scaffolds, followed by their induction into the osteogenic lineage. Our 3-D findings suggest that cell metabolism and proliferation increased between days 1 and 14, with deposition of extracellular matrix also observed up to 28 days. However, no noticeable difference could be detected in the extent of osteogenesis for PCL-TCP-Col scaffolds groups with the addition of heparin compared to identical control scaffolds without the addition of heparin. © 2009 Acta Materialia Inc.Publication The osteoblast-heparan sulfate axis: Control of the bone cell lineage(2005-09) Cool, S.M.; Nurcombe, V.; ORTHOPAEDIC SURGERYDuring osteogenesis, mesenchymal stem cells are recruited to the osteoblast lineage and progressively differentiate into osteoblasts that produce a mineralised extracellular matrix. Although most of the organic component of this matrix is comprised of collagen, growing evidence suggests the most bioactive element of a developing matrix is its heparan sulfate glycosaminoglycan complement. This species of linear, unbranched sugars contain protein-binding domains that regulate the flow of an astonishing number of mitogenic influences that coordinate mesenchymal stem cell commitment and growth, and ultimately, osteoblast phenotype. Among the heparan sulfate-binding factors known to be important to this process are sonic hedgehog, the fibroblast growth factors and their receptors, members of the transforming growth factor superfamily, as well as the collagens, laminins and fibronectins. How these sugars change during development to bring together the right combination of mitogenic/differentiative influences to trigger the successive phases of osteogenesis is currently the focus of intense research. © 2005 Elsevier Ltd. All rights reserved.Publication The stimulation of healing within a rat calvarial defect by mPCL-TCP/collagen scaffolds loaded with rhBMP-2(2009) Sawyer, A.A.; Song, S.J.; Chuan, P.; Cool, S.M.; Susanto, E.; Lam, C.X.F.; Woodruff, M.A.; Hutmacher, D.W.; ORTHOPAEDIC SURGERYBone morphogenetic proteins (BMPs) have been widely investigated for their clinical use in bone repair and it is known that a suitable carrier matrix to deliver them is essential for optimal bone regeneration within a specific defect site. Fused deposited modeling (FDM) allows for the fabrication of medical grade poly ε-caprolactone/tricalcium phosphate (mPCL-TCP) scaffolds with high reproducibility and tailor designed dimensions. Here we loaded FDM fabricated mPCL-TCP/collagen scaffolds with 5 μg recombinant human (rh)BMP-2 and evaluated bone healing within a rat calvarial critical-sized defect. Using a comprehensive approach, this study assessed the newly regenerated bone employing micro-computed tomography (μCT), histology/histomorphometry, and mechanical assessments. By 15 weeks, mPCL-TCP/collagen/rhBMP-2 defects exhibited complete healing of the calvarium whereas the non-BMP-2-loaded scaffolds showed significant less bone ingrowth, as confirmed by μCT. Histomorphometry revealed significantly increased bone healing amongst the rhBMP-2 groups compared to non-treated scaffolds at 4 and 15 weeks, although the % BV/TV did not indicate complete mineralisation of the entire defect site. Hence, our study confirms that it is important to combine microCt and histomorphometry to be able to study bone regeneration comprehensively in 3D. A significant up-regulation of the osteogenic proteins, type I collagen and osteocalcin, was evident at both time points in rhBMP-2 groups. Although mineral apposition rates at 15 weeks were statistically equivalent amongst treatment groups, micro-compression and push-out strengths indicated superior bone quality at 15 weeks for defects treated with mPCL-TCP/collagen/rhBMP-2. Consistently over all modalities, the progression of healing was from empty defect < mPCL-TCP/collagen < mPCL-TCP/collagen/rhBMP-2, providing substantiating data to support the hypothesis that the release of rhBMP-2 from FDM-created mPCL-TCP/collagen scaffolds is a clinically relevant approach to repair and regenerate critically-sized craniofacial bone defects. Crown Copyright © 2008.Publication Runx2, p53, and pRB status as diagnostic parameters for deregulation of osteoblast growth and differentiation in a new pre-chemotherapeutic osteosarcoma cell line (OS1)(2009) Pereira, B.P.; Aung, K.Z.; Pho, R.W.H.; Cool, S.M.; Nathan, S.S.; Zhou, Y.; Gupta, A.; Leong, D.T.; Salto-Tellez, M.; Van, Wijnen A.J.; Ling, L.; Galindo, M.; Stein, G.S.; ORTHOPAEDIC SURGERY; NATIONAL UNIVERSITY MEDICAL INSTITUTES; CANCER SCIENCE INSTITUTE OF SINGAPORE; PATHOLOGYPublication Long-term loading inhibits ERK1/2 phosphorylation and increases FGFR3 expression in MC3T3-E1 osteoblast cells(2006) Jackson, R.A.; Kumarasuriyar, A.; Nurcombe, V.; Cool, S.M.; ORTHOPAEDIC SURGERYPublication Modulating Mesenchymal Stem Cell Behavior Using Human Hair Keratin-Coated Surfaces(2015) Hartrianti, P; Ling, L; Goh, L.M.M; Ow, K.S.A; Samsonraj, R.M; Sow, W.T; Wang, S; Nurcombe, V; Cool, S.M; Ng, K.W; ORTHOPAEDIC SURGERYHuman mesenchymal stem cells (hMSCs) have shown great potential for therapeutic purposes. However, the low frequencies of hMSCs in the body and difficulties in expanding their numbers in vitro have limited their clinical use. In order to develop an alternative strategy for the expansion of hMSCs in vitro, we coated tissue culture polystyrene with keratins extracted from human hair and studied the behavior of cells from 2 donors on these surfaces. The coating resulted in a homogeneous distribution of nanosized keratin globules possessing significant hydrophilicity. Results from cell attachment assays demonstrated that keratin-coated surfaces were able to moderate donor-to-donor variability when compared with noncoated tissue culture polystyrene. STRO-1 expression was either sustained or enhanced on hMSCs cultured on keratin-coated surfaces. This translated into significant increases in the colony-forming efficiencies of both hMSC populations, when the cells were serially passaged. Human hair keratins are abundant and might constitute a feasible replacement for other biomaterials that are of animal origin. In addition, our results suggest that hair keratins may be effective in moderating the microenvironment sufficiently to enrich hMSCs with high colony-forming efficiency ex vivo, for clinical applications. © 2015 Pietradewi Hartrianti et al.