Our overall goal is to understand the mechanisms that determine how cells and tissues respond to implanted materials in order to improve the function of devices and combination products used clinically. Studies using titanium (Ti) substrates suggest that by understanding how surface morphology and chemistry modulate cell response, it may be possible to develop materials that control cell behavior through structural signaling, without the need for pharmacologic modification. The purpose of the present proposal is to use structured material surfaces to define which micron-scale and sub-micron scale topographical features regulate specific cell responses and to understand the underlying mechanisms involved. By controlling surface chemistry, we will also investigate how microarchitecture and hydrophilicity interact to control cell behavior. Our long term goal is to create rational biomimetic implants that facilitate normal tissue regeneration and repair. Our experimental hypothesis is that the physical and chemical properties of a surface determine integrin expression, influencing cellular signaling and response to factors that regulate osteogenesis, such as 1,25- dihydroxy vitamin D3 [1,25(OH)2D3] and estrogen. We will examine osteoblast behavior on defined Ti surfaces prepared using electochemical micromachining to produce micrometer scale structural features;submicron scale topography will be superimposed by chemically etching the surface under controlled conditions. Substrates will be designed that have comparable microarchitecture but different hydrophilicity. Cell culture models include: human osteoblast-like MG63 cells, normal human osteoblasts (NHOst cells), and the rat osteoblast-like cell line ROS 17/2.8.
Three specific aims are proposed:
Aim I. Examine the role of integrins in mediating the differential effects of surface design features on osteoblast phenotypic expression.
Aim II. Examine the role of substrate architecture in the response of osteoblasts to 1,25(OH)2D3 and 17b- estradiol.
Aim III. Examine the role of integrin-signaling in mediating the synergistic effect of surface design and steroid hormone action on osteoblast phenotypic expression. Thus, while our experiments are basic in nature, our intent is to conduct them in such a manner that the results can be applied to clinical implantology and tissue engineering.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
3R01AR052102-03S1
Application #
7847183
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Panagis, James S
Project Start
2009-06-10
Project End
2009-10-31
Budget Start
2009-06-10
Budget End
2009-10-31
Support Year
3
Fiscal Year
2009
Total Cost
$9,362
Indirect Cost
Name
Georgia Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30332
Boyan, Barbara D; Olivares-Navarrete, Rene; Berger, Michael B et al. (2018) Role of Wnt11 during Osteogenic Differentiation of Human Mesenchymal Stem Cells on Microstructured Titanium Surfaces. Sci Rep 8:8588
Berger, Michael B; Cohen, David J; Olivares-Navarrete, Rene et al. (2018) Human osteoblasts exhibit sexual dimorphism in their response to estrogen on microstructured titanium surfaces. Biol Sex Differ 9:30
Lotz, Ethan M; Berger, Michael B; Schwartz, Zvi et al. (2018) Regulation of osteoclasts by osteoblast lineage cells depends on titanium implant surface properties. Acta Biomater 68:296-307
Sedlaczek, Janina; Lohmann, Christoph H; Lotz, Ethan M et al. (2017) Effects of low-frequency ultrasound treatment of titanium surface roughness on osteoblast phenotype and maturation. Clin Oral Implants Res 28:e151-e158
Cohen, David J; Cheng, Alice; Sahingur, Kaan et al. (2017) Performance of laser sintered Ti-6Al-4V implants with bone-inspired porosity and micro/nanoscale surface roughness in the rabbit femur. Biomed Mater 12:025021
Cohen, D J; Cheng, A; Kahn, A et al. (2016) Novel Osteogenic Ti-6Al-4V Device For Restoration Of Dental Function In Patients With Large Bone Deficiencies: Design, Development And Implementation. Sci Rep 6:20493
Boyan, B D; Cheng, A; Olivares-Navarrete, R et al. (2016) Implant Surface Design Regulates Mesenchymal Stem Cell Differentiation and Maturation. Adv Dent Res 28:10-7
Lin, Zhao; Rodriguez, Nicholas E; Zhao, Junjun et al. (2016) Selective enrichment of microRNAs in extracellular matrix vesicles produced by growth plate chondrocytes. Bone 88:47-55
Lee, Erin M; Smith, Kathryn; Gall, Ken et al. (2016) Change in surface roughness by dynamic shape-memory acrylate networks enhances osteoblast differentiation. Biomaterials 110:34-44
Hotchkiss, Kelly M; Reddy, Gireesh B; Hyzy, Sharon L et al. (2016) Titanium surface characteristics, including topography and wettability, alter macrophage activation. Acta Biomater 31:425-434

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