Faculty Bibliography

Bone lacunocanalicular fluid flow ensures chemotransportation and provides a mechanical stimulus to cells. Traditional static cell-culture methods are ill-suited to study the intricacies of bone biology because they ignore the three-dimensionality of meaningful cellular networks and the lacunocanalicular system; furthermore, reliance on diffusion alone for nutrient supply and waste product removal effectively limits scaffolds to 2-3 mm thickness. In this project, a flow-perfusion system was custom-designed to overcome these limitations: eight adaptable chambers housed cylindrical cell-seeded scaffolds measuring 12 or 24 mm in diameter and 1-10 mm in thickness. The porous scaffolds were manufactured using a three-dimensional (3D) periodic microprinting process and were composed of hydroxyapatite/tricalcium phosphate with variable thicknesses, strut sizes, pore sizes and structural configurations. A multi-channel peristaltic pump drew medium from parallel reservoirs and perfused it through each scaffold at a programmable rate. Hermetically sealed valves permitted sampling or replacement of medium. A gas-permeable membrane allowed for gas exchange. Tubing was selected to withstand continuous perfusion for > 2 months without leakage. Computational modelling was performed to assess the adequacy of oxygen supply and the range of fluid shear stress in the bioreactor-scaffold system, using 12 x 6 mm scaffolds, and these models suggested scaffold design modifications that improved oxygen delivery while enhancing physiological shear stress. This system may prove useful in studying complex 3D bone biology and in developing strategies for engineering thick 3D bone constructs

Surface nano- and microtexturing techniques have been used to enhance osseointegration, but how these surfaces work is not well understood. Using the knowledge gained from the cell and molecular biology fields, tissue engineering studies, and their own work, the authors and other researchers have developed surfaces for in vitro and in vivo control of the function of cells and tissues. In the present article, the authors summarize what they know about the process of cell response to surfaces, and what they have done and can do to develop surfaces that control hard- and soft-tissue formation and integration of implants. This article is intended to add to the clinician's understanding of cell and surface interactions, explain why certain surfaces are currently used, and describe what surfaces clinicians may see in the future.

Mixed-phase TiO2 nanocomposite thin films consisting of anatase and rutile prepared on commercially pure Ti sheets via the electrochemical anodization and annealing treatments were investigated in terms of their photocatalytic activity for antibacterial use around dental implants. The resulting films were characterized by scanning electron microscopy (SEM), and X-ray diffraction (XRD). The topology was assessed by White Light Optical Profiling (WLOP) in the Vertical Scanning Interferometer (VSI) mode. Representative height descriptive parameters of roughness R a and R z were calculated. The photocatalytic activity of the resulting TiO2 films was evaluated by the photodegradation of Rhodamine B (RhB) dye solution. The antibacterial ability of the photocatalyst was examined by Aggregatibacter actinomycetemcomitans suspensions in a colony-forming assay. XRD showed that anatase/rutile mixed-phase TiO2 thin films were predominantly in anatase and rutile that were 54.6 wt% and 41.9 wt%, respectively. Craters (2-5 microm) and protruding hills (10-50 microm) on Ti substrates were produced after electrochemical anodization with higher R a and R z surface roughness values. Anatase/rutile mixed-phase TiO2 thin films showed 26% photocatalytic decolorization toward RhB dye solution. The number of colonizing bacteria on anatase/rutile mixed-phase TiO2 thin films was decreased significantly in vitro. The photocatalyst was effective against A. actinomycetemcomitans colonization.

The aim of this case study is to present a clinical approach to treatment of a mandibular intrabony cyst employing guided bone regeneration principles and protection of the mandibular nerve prior to implant placement. A treatment approach employing a combination of grafting materials and membranes was used to treat the cyst and protect the mandibular nerve prior to implant placement. Micro CT, as well as histology and histomorphometrics, was used to evaluate treatment outcomes. Histological inspection showed bone regeneration at the grafting site. Histomorphometric analysis of the biopsy core rendered a total bone percent area of 58.87% and 41.13% soft tissue. Out of the total bone percent area, 90.45% was revealed as vital bone and 9.55% was graft remnant. The grafted area is supporting an implant-supported prosthesis in full function.

Successful repair of craniofacial and periodontal tissue defects ideally involves a combined therapy that includes inflammation modulation, control of soft tissue infiltration, and bone regeneration. In this study, an anti-inflammatory polymer, salicylic acid-based poly(anhydride-ester) (SAPAE) and a three-dimensional osteoconductive ceramic scaffold were evaluated as a combined guided bone regeneration (GBR) system for concurrent control of inflammation, soft tissue ingrowth, and bone repair in a rabbit cranial defect model. At time periods of 1, 3, and 8 weeks, five groups were compared: (1) scaffolds with a solid ceramic cap (as a GBR structure); (2) scaffolds with no cap; (3) scaffolds with a poly(lactide-glycolide) cap; (4) scaffolds with a slow release SAPAE polymer cap; and (5) scaffolds with a fast release SAPAE polymer cap. Cellular infiltration and bone formation in these scaffolds were evaluated to assess inflammation and bone repair capacity of the test groups. The SAPAE polymers suppressed inflammation and displayed no deleterious effect on bone formation. Additional work is warranted to optimize the anti-inflammatory action of the SAPAE, GBR suppression of soft tissue infiltration, and stimulation of bone formation in the scaffolds and create a composite device for successful repair of craniofacial and periodontal tissue defects. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 655-664, 2014.

Bone healing can be significantly expedited by applying electrical stimuli in the injured region. Therefore, a three-dimensional (3D) ceramic conductive tissue engineering scaffold for large bone defects that can locally deliver the electrical stimuli is highly desired. In the present study, 3D conductive scaffolds were prepared by employing a biocompatible conductive polymer, ie, poly(3,4-ethylenedioxythiophene) poly(4-styrene sulfonate) (PEDOT:PSS), in the optimized nanocomposite of gelatin and bioactive glass. For in vitro analysis, adult human mesenchymal stem cells were seeded in the scaffolds. Material characterizations using hydrogen-1 nuclear magnetic resonance, in vitro degradation, as well as thermal and mechanical analysis showed that incorporation of PEDOT:PSS increased the physiochemical stability of the composite, resulting in improved mechanical properties and biodegradation resistance. The outcomes indicate that PEDOT:PSS and polypeptide chains have close interaction, most likely by forming salt bridges between arginine side chains and sulfonate groups. The morphology of the scaffolds and cultured human mesenchymal stem cells were observed and analyzed via scanning electron microscope, micro-computed tomography, and confocal fluorescent microscope. Increasing the concentration of the conductive polymer in the scaffold enhanced the cell viability, indicating the improved microstructure of the scaffolds or boosted electrical signaling among cells. These results show that these conductive scaffolds are not only structurally more favorable for bone tissue engineering, but also can be a step forward in combining the tissue engineering techniques with the method of enhancing the bone healing by electrical stimuli.

It is important to develop functional transmucosal implant surfaces that reduce the number of initially adhering bacteria and they need to be modified to improve the anti-bacterial performance. Commercially pure Ti sheets were anodized in an electrolyte containing ethylene glycol, distilled water and ammonium fluoride at room temperature to produce TiO2 nanotubes. These structures were then annealed at 450 degrees C to transform them to anatase. As-annealed TiO2 nanotubes were then treated in an electrolyte containing 80.7 g/L NiSO4 .7H2O, 41 g/L MgSO4 .7H2O, 45 g/L H3BO3, and 1.44 g/L Ag2SO4 at 20 degrees C by the application of 9 V AC voltage for doping them with silver. As-annealed TiO2 nanotubes and as-annealed Ag doped TiO2 nanotubes were evaluated by SEM, FESEM, and XRD. Antibacterial activity was assessed by determining the adherence of A. actinomycetemcomitans, T. forsythia, and C. rectus to the surface of the nanotubes. Bacterial morphology was examined using an SEM. As-annealed Ag doped TiO2 nanotubes revealed intense peak of Ag. Bacterial death against the as-annealed Ag doped TiO2 nanotubes were detected against A. actinomycetemcomitans, T. forsythia, and C. rectus indicating antibacterial efficacy.