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Biomaterial Engineering Solution Labratory |
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Tissue EngineeringTissue engineering consists of three categories: scaffold, cell and signals. We focus on optimization of scaffold design and fabrication to mimic the in vivo natural environment, to aid and induce tissue regeneration. In our lab, bioceramics, polymer and composite scaffolds with different composition, geometry structure and shapes are fabricated using different techniques, and their effect on bone cell and bone tissue have been evaluated. Currently our research is in the field of controlled biodegradable rate of scaffolds, thereby achieving a controlled release rate of growth factor and drugs. In addition, we are interested in applying the developing biomaterials for specific diseases such as bony birth defects and cancer therapy. A. Biomaterial design, fabrication and characterizationIn our lab, biomaterials are designed and fabricated on basis of the application. The chemical and physical properties of the developed biomaterials are characterized using all kinds of facilities (see facility section). Figure 1 is an example of three dimensional calcium phosphate scaffold.
Figure 1 Representative Mciro CT images of porous calcium phosphate scaffolds. Left figure is with 3-dimension reconstruction and right figure is with 2-dimension section. Figure 1 shows the interconnective macroporous structure which assembles the trabecular bone. The porous structure and chemistry of calcium phosphate scaffold are very critical to help bone tissue regeneration as a template.
B. Biological evaluation by in vitro cell culture and in vivo animal studyBiological evaluation is very critical to biomaterial research and development. In our lab, we use in vitro cell culture to screen the formula and geometry of the developed biomaterial and then we use animal model to evaluate the biomaterial - tissue response in vivo. Figure 2 is an example of the osteoblast precursor cell responses to different composition of calcium phosphate scaffold. Figure 3 is an example of calcium phosphate scaffold as a carrier for growth factor delivery in vivo.
Figure 2 Alkaline phosphatase specific activity of osteoblast precursor cells in calcium phosphate scaffolds. Alkaline phosphatase production is an indicator of osteoblast differentiation. Beta-tricalcium phosphate scaffolds significantly enhanced osteoblast differentiation compared to hydroxyapatite scaffolds during a 3-week incubation.
Figure 3 Histology of bone formation with rhBMP-2 loaded β-tricalcium phosphate scaffold in implanted muscle of mice at 14 days after implantation. The specimen is stained with HE stain (original magnification X 25). WB = woven bone, MA = bone marrow, M = muscle. At 14 days after implantation, woven bone and immature marrow was observed in the rhBMP-2 loaded beta-tricalcium phosphate scaffold.
Surface engineeringSurface engineering focuses on implant surface chemistry, texture and mechanical properties to improve performance of dental and orthopedic implant devices. In clinical, osseointegration, which is defined as the direct bone-implant contact, is critical for initial fixation and long-term success of endosseous dental and orthopedic implants. The initial host response after implantation is similar to a common bone wound modified by the presence of the implant. The new bone formation in the gap between the implant surface and host bone consists of three categories: osteogenesis at the implant surface (contact osteogenesis), within the surgical microgap at sites of neovasculization, and the surgical host bone margin (distance osteogenesis). As such, surface features that may influence any or all of these rates of bone formation will have the potential to enhance osseointegration. In our lab, the implant surface chemistry, texture and mechanical properties have been modified via plasma spraying, sputtering, ion implantation and chemical treatment. The chemistry include titanium, hydroxyapatite, zirconia, titania, and biomolecule and growth factor. The enhancement of osseointegraion has been evidenced by in vitro cell culture and in vivo animal study. We give some examples in the implant surface modification, characterization, and biological evaluation in the following.
Figure 4 Scanning electron micrographs of plasma sprayed hydroxyapatite coating (a) and plasma sprayed titanium coating (b). The plasma sprayed coatings roughen the surface texture which helps with osseointegration.
Figure 5 Scanning electron micrographs of nanoscale implant surfaces. Using different techniques, we can fabricate different nanoscale morphologies. For example, we can use vapor based deposition to make dense surface with different nanosize grains. We can use solution based deposition to produce porous surfaces with different nanosize pores. Also, we can use solid based deposition to prepare nano rods with different nanosize diameters. The amazing thing is the different nano patterns have different effects on cell responses, which may allow us to manipulate the cell response as we expect.
Figure 6 Osteoblast cells adhere, migrate and grow into the plasma sprayed titanium porous coating, suggesting excellent biocompatibility of the implant surface.
Figure 7 Osseointegration of new bone-titanium interface with fluorescent microscopy (original X100). Yellow indicates new bone; black indicates titanium. The plasma sprayed functionally porous graded titanium coated samples were placed into dog femur. At 8 weeks after implantation, the new bone not only directly contacted with the implant, but also grew into the interconnective pores and formed mechanical interlocking, thereby enhancing the fixation of implants with bone.
Figure 8 Osseointegration of new bone-titanium interface by scanning electron microscopy (original X 500). Yellow arrows indicate holes within coating; white arrows indicate line analysis. The plasma sprayed functionally porous graded titanium coated samples were placed into dog femur. At 8 weeks after implantation, a lot of pores were observed within the porous coatings and these pores were rich in calcium and phosphorus elements with the Ca/P ratio of 1.14 to 1.88, indicating that the new bone does grow into the pores and form mechanical interlocking, which helps with the implant fixation.
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