Our research interests include the use of molecular and cell biology approaches together with engineering principles in developing cellular and tissue engineering strategies for organ regeneration and assessment of human health risk. Our research objectives can be categorized into three major areas:
1. Bone tissue engineering
2. Cell and tissue based biosensors
3. Cancer cell metastasis
Bone Tissue Engineering: During the last decade a number of bone tissue-engineering strategies have been proposed that promise to overcome the limitations of the current therapies. These strategies often require the use of degradable porous scaffolds that can promote the migration of cells from the surrounding tissue or the growth of bone forming cells seeded within the porous network of the scaffold. Most of these bone tissue-engineering approaches envision seeding scaffolds with multipotent adult stem cells that have the potential to enhance new bone formation and can be obtained from the patient's bone marrow. Techniques have been developed that allow osteoprogenitor cells from the bone marrow to be selected and expanded in culture allowing the generation of a large transplantable cell population from a small biopsy. Scaffolds can be seeded with these cells and transplanted to the defect site or cultured in vitro for an additional period prior to transplantation. During this period the cells will proliferate and also deposit bioactive extracellular matrix and growth factors that add osteoinductive potential to the scaffold. The emphasis of our studies is to develop novel strategies for the creation of three-dimensional biodegradable cell/scaffold constructs that are rich in growth factors and extracellular matrix for bone regeneration and repair.
Cell and Tissue Based Biosensors: Biosensors are devices that incorporate biological and physicochemical elements and produce a signal that is related to the presence of an analyte. The analyte is a biomolecule that affects human health. Traditional biosensors identify analytes that are well characterized but fail to identify the presence of unknown agents that can be potentially harmful. Cellular assemblies that mimic tissues can become inherent components of biosensors that will allow prompt and accurate assessment of the environmental and the human health risk posed by a wide variety of agents. Significant efforts in our research group are directed towards the development of three dimensional cell/scaffold constructs that can respond in the presence of harmful agents.
Cancer Cell Metastasis: Cancer cell metastasis is a complex process involving the transport of tumor cells and multiple sequential interactions between tumor cells and the host tissue microenvironment. The identification of these processes can create methodologies that can interrupt the metastatic process. Most of the metastatic tumors in bone cause bone osteolysis but prostate tumor metastasis leads to the formation of bone deposits around the tumor cells. Most of the patients with prostate cancer eventually develop bone cancer. We are investigating the mechanisms leading to cancer cell metastasis in bone in order to provide more effective treatments for the prevention of bone cancer metastasis.
Research Web Sites
Bioengineering Center - Home Page
1. Karami, D., Richbourg, N., Sikavitsas, V.I., (2019), “Dynamic In Vitro Models for Tumor Tissue Engineering.” Cancer Letters, doi: 10.1016/j.canlet.2019.01.043.
2. O.E. Kadri, C. Williams 3rd, V. Sikavitsas, R.S. Voronov, (2018), “Numerical accuracy comparison of two boundary conditions commonly used to approximate shear stress distributions in tissue engineering scaffolds cultured under flow perfusion.” Int. J. Numer. Method Biomed. Eng. doi: 10.1002/cnm.3132
3. Williams, C. 3rd, Kadri, O.E., Voronov, R.S., Sikavitsas, V.I., (2018), “Time-Dependent Shear Stress Distributions during Extended Flow Perfusion Culture of Bone Tissue Engineered Constructs.” Fluids, doi: 10.3390/fluids3020025
4. J.E. Trachtenberg, M. Santoro, C. Williams, III, C.M. Piard, B.T. Smith, J.K. Placone, B.A. Menegaz, E.R. Molina, S.-E. Lamhamedi-Cherradi, J.A. Ludwig, V.I. Sikavitsas, J.P. Fisher, A.G. Mikos, (2018), “Effects of Shear Stress Gradients on Ewing Sarcoma Cells Using 3D
Printed Scaffolds and Flow Perfusion” ACS Biomater. Sci. Eng. 4, 347−356.
5. A.D. Simmons and V.I. Sikavitsas (2018), “Monitoring Bone Tissue Engineered (BTE) Constructs Based on the Shifting Metabolism of Differentiating Stem Cells.” Annals of Biomedical Engineering, 46(1), 37-47.
6. B. Engebretson, Z.R. Mussett, and V.I. Sikavitsas (2018), “The effects of varying frequency and duration of mechanical stimulation on a tissue-engineered tendon construct.” Connective Tissue Research, 59(2), 167-177.
7. A.D. Simmons, C. Williams, A. Degoix, and V.I. Sikavitsas (2017), “Sensing metabolites for the monitoring of tissue engineered construct cellularity in perfusion bioreactors”. Biosensors & Bioelectronics, 90, 443-449.
8. J.J. Krais, N. Virani, P.H. McKernan, Q. Nguyen, K.M. Fung, V.I. Sikavitsas, C. Kurkjian, R.G. Harrison, (2017) “Antitumor Synergism and Enhanced Survival with a Tumor Vasculature-Targeted Enzyme Prodrug System, Rapamycin, and Cyclophosphamide” Molecular Cancer Therapeutics, 16(9), 1855-1865.
9. B.W. Engebretson, Z. Mussett, and Vassilios Sikavitsas (2017), “Tenocytic Extract and Mechanical Stimulation in a Tissue-Engineered Tendon Construct Increases Cellular Proliferation and ECM Deposition”, Biotechnology Journal, 12, 1600595.
10. T.A. Alam, Q.L. Pham, V.I. Sikavitsas, D.V. Papavassiliou, R.L. Shambaugh, and R.S. Voronov (2016), “Image-based modeling: A novel tool for realistic simulations of artificial bone cultures”, Technology, 4(4) 229-233.
11. B.D. Van Rite, J.J. Krais, M. Cherry, V.I. Sikavitsas, C. Kurkjian, and R.G. Harrison, (2013), “Antitumor activity of an enzyme prodrug therapy targeted to the breast tumor vasculature”. Cancer Invest., 31(8), 505-510.
12. B.W. Engebretson and V.I. Sikavitsas (2013), “Long Term In Vivo Effect of PEG Bone Tissue Engineering Scaffolds” J of Long Term Effects in Medical Implants, 22(3), 211–218
13. R.S. Voronov, S.B. Van Gordon, R.L. Shambaugh, D.V. Papavassiliou, and V.I. Sikavitsas, (2013), “3D Tissue-Engineered Construct Analysis via Conventional High-Resolution Microcomputed Tomography Without X-Ray Contrast” Tissue Engineering Part C, 19, 327-335.
14. B.C. Landy, S.B. Van Gordon, P.S. McFetridge, M. Jarman-Smith, and V.I. Sikavitsas (2012) “Mechanical and in vitro investigation of a porous PEEK foam for medical device implants” J Appl Biomaterials & Functional Materials, 24(11), 35-44
15. N.H. Pham, R.S. Voronov, S.B. Van Gordon, V.I. Sikavitsas, and D.V. Papavassiliou (2012), “Predicting the stress distribution within scaffolds with ordered architecture” Biorheology, 49, 235-247.
16. S. Liu, D.B. Brunski, V.I. Sikavitsas, M.B. Johnson, and A.Striolo, (2012) “Friction coefficients for mechanically damaged bovine articular cartilage” Biotech Bioeng, 109, 1767-1778.
17. R.I. Issa, B. Engebretson, L. Rustom, P.S. McFetridge, and V.I. Sikavitsas, (2011) “The effect of cell seeding density on the cellular and mechanical properties of a mechanostimulated tissue engineered tendon” Tissue Eng Part A, 17, 1479-1487
18. S.B. Van Gordon, R.S. Voronov, T.B. Blue, R.L. Shambaugh, D.V. Papavassiliou, and V.I. Sikavitsas, (2011) “Effects of Scaffold Architecture on Preosteoblastic Cultures under Continuous Fluid Shear” Industrial & Engineering Chemistry Research, 50(2), 620-629.
19. J. Alvarez Barreto, B. Landy, L. Place, S.B. Van Gordon, P.L. DeAngelis, and V.I. Sikavitsas, (2011) “Enhanced Osteoblastic Differentiation of Mesenchymal Stem Cells Seeded on RGD Functionalized PLLA Scaffolds and Cultured in a Flow Perfusion Bioreactor” Journal of Tissue Engineering and Regenerative Medicine, 5, 464-475.
20. S. Liu, V.I. Sikavitsas, and A. Striolo, (2011), “Experimental Friction Coefficients for Bovine Cartilage Measured with a Pin-on-Disk Tribometer: Testing Configuration and Lubricant Effects” Annals Biomed Eng, 39, 132-146.
21. R.S. Voronov, S. van Gordon, V.I. Sikavitsas, and D.V. Papavassiliou, (2011) “Efficient Lagrangian scalar tracking method for reactive local mass transport simulation through porous media” Int. J. for Num Meth in Fluids, 67, 501-517.
22. R.S. Voronov, S. van Gordon, V.I. Sikavitsas, and D.V. Papavassiliou, (2010), “Distribution of flow-induced stresses in highly porous media” Applied Physics Letters, 97, 024101.
23. R.S. Voronov, S. van Gordon, V.I. Sikavitsas, and D.V. Papavassiliou, (2010) “Computational modeling of flow-induced shear stresses within 3D salt-leached porous scaffolds imaged via micro-CT.” J. Biomechanics 43, 1279-1286
24. R. Abousleiman, Y. Reyes, P.S. McFetridge, and V.I. Sikavitsas (2009) “Tendon Tissue Engineering Using Cell Seeded Umbilical Veins Cultured in a Mechanical Stimulator” Tissue Engineering Part A 15, 787-795
25. R. Abousleiman, Y. Reyes, P.S. McFetridge, and V.I. Sikavitsas (2008). “The Human Umbilical Vein: a Novel Scaffold for Musculoskeletal Soft Tissue Regeneration”, Artificial Organs, 32, 735-742
26. J.F. Alvarez-Barreto, M. Shreve, P. DeAnglelis, and V.I. Sikavitsas, (2007). “Preparation of a functionally flexible, three-dimensional, biomimetic poly (L-lactic acid) scaffold with improved cell adhesion”, Tissue Eng. 13, 1205-1217
27. J.F. Alvarez-Barreto, and V.I. Sikavitsas, (2007). “Improved mesenchymal stem cell seeding on RGD-modified poly(L-lactic acid) scaffolds using flow perfusion”, Macromolecular Biosciences, 7, 579-588.
28. H. Castano-Izguierdo, J.F. Alvarez-Barreto, J. van den Dolder, J.A. Jansen, A.G. Mikos, and V.I. Sikavitsas, (2007). “Pre-culture period of mesenchymal stem cells in osteogenic media influences their in vivo bone forming potential.” J. Biomed. Mater. Res., 82A, 129-138
29. J.F. Alvarez-Barreto, S.M. Linehan, R.L. Shambaugh, and V.I. Sikavitsas (2007). “Flow perfusion improves seeding of tissue engineering scaffolds with different architectures” Annals Biomed Eng, 35, 429-442.
30. R. Abousleiman, and V.I. Sikavitsas (2006). “Bioreactors for tissues of the musculoskeletal system” Adv. Exp. Med. Bio. 585, 243-259.
31. R.G. Harrison, M.U. Nollert, D.W. Schmidtke, and V.I. Sikavitsas, (2006). “The research proposal in biochemical and biological engineering courses” Chem. Eng. Education, 40, 323-326.
32. N. Datta, Q.P. Pham, U. Sharma, V.I. Sikavitsas, J.A. Jansen, A.G. Mikos, (2006). “In vitro generated extracellular matrix and fluid shear stress synergistically enhance 3D osteoblastic differentiation” Proc. Nat. Acad. Sci. USA, 103, 2488-2493
33. N. Datta, H.L Holtorf, V.I. Sikavitsas, J.A Jansen, and A.G. Mikos (2005). “Effect of bone extracellular matrix synthesized in vitro on the osteoblastic differentiation of marrow stromal cells.” Biomaterials, 26, 971-977
34. V.I. Sikavitsas, G.N. Bancroft, J.J. Lemoine, M.A.K. Liebschner, M. Dauner, and A.G. Mikos (2005). “Flow perfusion enhances the mineral deposition of marrow stromal osteoblasts in biodegradable non-woven fiber mesh scaffolds.” Annals of Biomedical Engineering 33, 63-70.
35. H. Castano, E.A. O’Rear, P.S. McFetridge, and V.I. Sikavitsas (2004). “Polypyrrole thin films formed by admicellar polymerization promote the osteogenic differentiation of mesenchymal stem cells” Macromolecular Biosciences, 4, 785-794
36. V.I. Sikavitsas*, G.N. Bancroft*, H.L Holtorf, J.A Jansen, and A.G. Mikos (2003). “Mineralized matrix deposition by marrow stromal osteoblasts in 3D perfusion culture increases with increasing fluid shear forces.” Proceedings of the National Academy of Sciences of the USA, 100, 14683-14688 (* first authorship equally shared).
37. V.I. Sikavitsas*, J. van den Dolder*, G.N. Bancroft*, J.A. Jansen, and A.G. Mikos (2003). “Influence of the in vitro culture period on the in vivo performance of cell/titanium bone tissue engineered constructs using a rat critical size defect model.” Journal of Biomedical Materials Research, 67A, 944-951 (* first authorship equally shared)
38. M.E. Gomes, V.I. Sikavitsas, E. Behravesh, R.L. Ruis, and A.G. Mikos (2003). “Effect of flow perfusion on the osteogenic differentiation of bone marrow stromal cells on starch based thee-dimensional scaffolds.” Journal of Biomedical Materials Research, 67A, 87-95.
39. E. Behravesh, V.I. Sikavitsas, and A.G. Mikos (2003) “Quantification of ligant surface concentration of bulk modified biomimetic hydrogels.” Biomaterials, 24, 4365-4374.
40. G.N. Bancroft*, V.I. Sikavitsas*, and A.G. Mikos (2003). “Design of a flow perfusion bioreactor system for bone tissue engineering applications.” Tissue Engineering, 9, 549-554 (* first authorship equally shared).
41. J. van den Dolder, G.N. Bancroft, V.I. Sikavitsas, P.H.M. Spauwen, A.G. Mikos, and J.A. Jansen (2003). “The effect of fibronectin and collagen type I coated titanium fiber mesh on proliferation and differentiation of osteogenic cells” Tissue Engineering, 9, 505-515.
42. J. van den Dolder*, G.N. Bancroft*, V.I. Sikavitsas*, P.H.M. Spauwen, J.A. Jansen, and A.G. Mikos (2003) “Flow perfusion culture of marrow stromal osteoblasts in titanium fiber mesh.” Journal of Biomedical Materials Research, 64A, 235-241
43. G.N. Bancroft*, V.I. Sikavitsas*, J. van den Dolder, T.L. Sheffield, J.A. Jansen, C.G. Ambrose, and A.G. Mikos (2002). “Fluid flow increases mineralized matrix deposition in three-dimensional perfusion culture of marrow stromal osteoblasts in a dose-dependent manner.” Proceedings of the National Academy of Sciences of the USA, 99, 12600-12605
44. V.I. Sikavitsas, J.M. Nitsche and T.J. Mountziaris (2002). “Transport and kinetic processes underlying biomolecular interactions in the BIACORE optical biosensor.” Biotechnology Progress, 18, 885-897.
45. V.I. Sikavitsas*, G.N. Bancroft*, and A.G. Mikos (2002). “Formation of three-dimensional cell/polymer constructs for bone tissue engineering in a spinner flask and a rotating wall vessel bioreactor.” Journal of Biomedical Materials Research, 62, 136-148
46. V.I. Sikavitsas, J.S. Temenoff and A.G. Mikos (2001). “Biomaterials and bone mechanotransduction.” Biomaterials, 22: 2581-2593.
47. E.S. Kikkinides, V.I. Sikavitsas, and R.T. Yang (1995). “Natural gas desulfurization by adsorption: feasibility and multiplicity of cyclic steady states.” Industrial & Engineering Chemistry Research, 34, 255-262
48. V.I. Sikavitsas, R.T. Yang, M.A. Burns and E.J. Langenmayr (1995). “Magnetically stabilized fluidized bed for gas separations: Olefin-Paraffin separations by p-complexation.” Industrial & Engineering Chemistry Research, 34, 2873-2880.
49. V.I. Sikavitsas, and R.T. Yang (1995). “Predicting multicomponent diffusivities for diffusion on surfaces and in molecular sieves with energy heterogeneity.” Chemical Engineering Science, 50, 3057-3065.
50. V.I. Sikavitsas, and R.T. Yang (1995). “Kinetic theory for predicting multicomponent diffusivities from pure-component diffusivities for surface diffusion and diffusion in molecular sieves.” Chemical Engineering Science, 50, 3319-3322.