Surface Microtopography Modulation of Biomaterials for Bone Tissue Engineering Applications

The ultimate goal of this project is to develop a biodegradable and implantable scaffold with precise surface topographies that can provide osteoconductive stimuli to connective tissue progenitor cells (CTPs), and subsequently, enhance bone regeneration applications without the complications of autogenous cancellous bone grafts. This dissertation presents the modification of surface microtextures to provide osteoconductive stimuli to CTPs for bone regeneration applications. First, the effect of surface topography on cell proliferation and osteogenic differentiation was validated through experiments using surface post microtextures and CTPs. Post microtextures accelerated CTP growth behaviors compared to smooth polydimethylsiloxane (PDMS) and standard cell culture dishes. Second, soft lithographic techniques were used to develop PDMS post microtextures with varying geometry and arrangement. 10 m diameter post microtextures with various inter-spaces (5, 10, 20, and 40 m) and post heights (5, 10, 20, and 40 m) were developed, and cultured with CTPs to establish optimal and precise surface post microtextures that can provide CTPs with an osteoconductive environment. Cells on post microtextures with 10 m height and 10 m inter-space exhibited higher cell number than other micro-posts with different

[1]  D. Seabold,et al.  Implant Surface Roughness Affects Osteoblast Gene Expression , 2003, Journal of dental research.

[2]  D. Landolt,et al.  Osteoblast-like cells are sensitive to submicron-scale surface structure. , 2006, Clinical oral implants research.

[3]  B. Boyan,et al.  Integrin beta1 silencing in osteoblasts alters substrate-dependent responses to 1,25-dihydroxy vitamin D3. , 2006, Biomaterials.

[4]  D. Butler,et al.  In vitro characterization of mesenchymal stem cell-seeded collagen scaffolds for tendon repair: effects of initial seeding density on contraction kinetics. , 2000, Journal of biomedical materials research.

[5]  BIODEGRADABLE POLYMER MICRONEEDLES FOR CONTROLLED-RELEASE DRUG DELIVERY , 2011 .

[6]  A. Mata,et al.  Characterization of Polydimethylsiloxane (PDMS) Properties for Biomedical Micro/Nanosystems , 2005, Biomedical microdevices.

[7]  G. Vunjak‐Novakovic,et al.  Tissue engineered bone grafts: biological requirements, tissue culture and clinical relevance. , 2008, Current stem cell research & therapy.

[8]  A Curtis,et al.  Topographical control of cells. , 1997, Biomaterials.

[9]  Richard O. Hynes,et al.  Integrins: Versatility, modulation, and signaling in cell adhesion , 1992, Cell.

[10]  R. Stromberg,et al.  A flow system for the study of shear forces upon cultured endothelial cells. , 1986, Journal of biomechanical engineering.

[11]  X. Wen,et al.  Microrough surface of metallic biomaterials: a literature review. , 1996, Bio-medical materials and engineering.

[12]  B. Larson,et al.  Human Multipotent Stromal Cells Undergo Sharp Transition from Division to Development in Culture , 2008, Stem cells.

[13]  John P Fisher,et al.  Synthesis and properties of cyclic acetal biomaterials. , 2007, Journal of biomedical materials research. Part A.

[14]  K. Burridge,et al.  Interactions between Integrins and the Cytoskeleton: Structure and Regulation , 1994 .

[15]  Douglas W Hamilton,et al.  Comparative response of epithelial cells and osteoblasts to microfabricated tapered pit topographies in vitro and in vivo. , 2007, Biomaterials.

[16]  K. D. Groh,et al.  The Development of Surface Roughness and Implications for Cellular Attachment in Biomedical Applications , 2001 .

[17]  K. J. Long,et al.  Surface roughness, porosity, and texture as modifiers of cellular adhesion. , 1996, Tissue engineering.

[18]  Joe Tien,et al.  Mechanotransduction at cell-matrix and cell-cell contacts. , 2004, Annual review of biomedical engineering.

[19]  M. Forwood,et al.  Inducible cyclo‐oxygenase (COX‐2) mediates the induction of bone formation by mechanical loading in vivo , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[20]  C. M. Agrawal,et al.  Biodegradable polymeric scaffolds for musculoskeletal tissue engineering. , 2001, Journal of biomedical materials research.

[21]  S. Retterer,et al.  Microfabricated Plastic Devices from Silicon Using Soft Intermediates , 2003 .

[22]  D. Donati,et al.  Historical review of bone prefabrication , 2008, La Chirurgia degli organi di movimento.

[23]  S. K. Zaidi,et al.  Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression , 2004, Oncogene.

[24]  S. Keshavjee,et al.  Cell-based tissue engineering for lung regeneration. , 2007, American journal of physiology. Lung cellular and molecular physiology.

[25]  Y. Iwamoto,et al.  Fluid Shear Stress Increases Transforming Growth Factor Beta 1 Expression in Human Osteoblast-like Cells: Modulation by Cation Channel Blockades , 1998, Calcified Tissue International.

[26]  H. Ohgushi,et al.  Bone augmentation by bone marrow mesenchymal stem cells cultured in three-dimensional biodegradable polymer scaffolds. , 2009, Journal of biomedical materials research. Part A.

[27]  D. Hutmacher,et al.  Scaffolds in tissue engineering bone and cartilage. , 2000, Biomaterials.

[28]  Indu Bala,et al.  PLGA nanoparticles in drug delivery: the state of the art. , 2004, Critical reviews in therapeutic drug carrier systems.

[29]  J. Aubin,et al.  Bone stem cells , 1998, Journal of cellular biochemistry.

[30]  Dongan Wang,et al.  Novel mesoporous silica-based antibiotic releasing scaffold for bone repair. , 2009, Acta biomaterialia.

[31]  W. Saltzman,et al.  Micron-scale positioning of features influences the rate of polymorphonuclear leukocyte migration. , 2001, Biophysical journal.

[32]  V. Nurcombe,et al.  Substrate induction of osteogenesis from marrow-derived mesenchymal precursors. , 2005, Stem cells and development.

[33]  E. D. Rekow,et al.  Performance of hydroxyapatite bone repair scaffolds created via three-dimensional fabrication techniques. , 2003, Journal of biomedical materials research. Part A.

[34]  P. Bohn,et al.  Three-dimensional integrated microfluidic architectures enabled through electrically switchable nanocapillary array membranes. , 2007, Biomicrofluidics.

[35]  Yordan Kostov,et al.  Functional cardiac cell constructs on cellulose-based scaffolding. , 2004, Biomaterials.

[36]  Sidney A. Welch.  CELLULOSE ACETATE , 1924 .

[37]  Sami Alom Ruiz,et al.  Shear force at the cell-matrix interface: enhanced analysis for microfabricated post array detectors. , 2005, Mechanics & chemistry of biosystems : MCB.

[38]  Wei Wang,et al.  Lab-on-a-print: from a single polymer film to three-dimensional integrated microfluidics. , 2009, Lab on a chip.

[39]  B. Kasemo,et al.  A novel cell force sensor for quantification of traction during cell spreading and contact guidance. , 2007, Biophysical journal.

[40]  K. Anselme,et al.  Osteoblast adhesion on biomaterials. , 2000, Biomaterials.

[41]  Shuvo Roy,et al.  A three-dimensional scaffold with precise micro-architecture and surface micro-textures. , 2009, Biomaterials.

[42]  J Amédée,et al.  Function of linear and cyclic RGD-containing peptides in osteoprogenitor cells adhesion process. , 2002, Biomaterials.

[43]  Joe Tien,et al.  Repositioning of cells by mechanotaxis on surfaces with micropatterned Young's modulus. , 2003, Journal of biomedical materials research. Part A.

[44]  James Steele,et al.  The Human Bone , 2000 .

[45]  Z. Schwartz,et al.  [The role of surface roughness in promoting osteointegration]. , 2003, Refu'at ha-peh veha-shinayim.

[46]  A Curtis,et al.  Nantotechniques and approaches in biotechnology. , 2001, Trends in biotechnology.

[47]  D. Burr,et al.  Mechanotransduction in bone: osteoblasts are more responsive to fluid forces than mechanical strain. , 1997, The American journal of physiology.

[48]  J. Voldman,et al.  A PHOTOPATTERNABLE SILICONE FOR BIOMEMS APPLICATIONS , 2007 .

[49]  John P Fisher,et al.  Synthesis and characterization of cyclic acetal based degradable hydrogels. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[50]  R. G. Harrison,et al.  The reaction of embryonic cells to solid structures , 1914 .

[51]  K E Healy,et al.  Kinetics of bone cell organization and mineralization on materials with patterned surface chemistry. , 1996, Biomaterials.

[52]  B. Boyan,et al.  Response of normal female human osteoblasts (NHOst) to 17beta-estradiol is modulated by implant surface morphology. , 2002, Journal of biomedical materials research.

[53]  J. Planell,et al.  Human-osteoblast proliferation and differentiation on grit-blasted and bioactive titanium for dental applications , 2002, Journal of materials science. Materials in medicine.

[54]  D. Hamilton,et al.  The effect of substratum topography on osteoblast adhesion mediated signal transduction and phosphorylation. , 2007, Biomaterials.

[55]  Kevin M. Shakesheff,et al.  Tissue engineering: strategies, stem cells and scaffolds , 2008, Journal of anatomy.