Faculty Bibliography

Bone defects are associated with trauma, congenital disorders, non-unions, or infections following surgical procedures. Defects which are unable to heal spontaneously are categorized as "critical sized" and are commonly treated using bone grafts in an effort to facilitate bone regeneration and stabilization. Grafting materials can be either natural or synthetic, each having their respective advantages and disadvantages. Synthetic bone grafts are favored due to their ability to be tailored to exhibit desired properties and geometric configurations. β-tricalcium phosphate (β-TCP) is a synthetic grafting material that has been widely utilized for regenerative purposes due to its favorable osteoconductive properties. In combination with 3D printing, grafting materials can be further customized with respect to their macro and micro features. One way to customize devices is by using 3D printing and varying the surface area, by varying the internal component measurements. The objective of this study was to compare the effect of porosity and surface area of 3D printed β-TCP scaffolds with different strut diameters and the effect on cell proliferation in vitro. ß-TCP scaffolds were printed using a custom-built 3D direct-write micro printer with syringes equipped with different extrusion tip diameters (fdiameter: 200 µm, 250 µm and 330 µm). After sintering and post processing, scaffolds were subjected to micro-computed tomography (µCT) and a Scanning Electron Microscope (SEM) to evaluate surface area and porosity, respectively. Compressive strength was assessed using a universal testing machine. Cell proliferation was assessed through cellular viability, using human osteoprogenitor cells. The surface area of the scaffolds was found to increase with smaller strut diameters. Statistically significant differences (p<0.05) were detected for cellular proliferation, between the smallest extrusion diameter, 200 μm, and the largest diameter, 330 μm, after 48-, 72-, and 168-hours. No statistical significances were detected (p>0.05) with regards to the mechanical properties between groups. This study demonstrated that a smaller diameter rod yielded a higher surface area resulting in increased levels of cellular proliferation. Therefore, tailoring rod dimensions has the capacity to enhance cellular adhesion and ultimately, proliferation.

BACKGROUND:We aimed to histomorphometrically evaluate the effects of Leucocyte-Platelet-Rich Fibrin (L-PRF), with and without the combination of a bone grafting material, for alveolar ridge preservation using an in vivo canine model. MATERIAL AND METHODS/METHODS:Seven dogs (Female Beagles, ~18-month-old) were acquired for the study. L-PRF was prepared from each individual animal by drawing venous blood and spinning them through a centrifuge at 408 RCF-clot (IntrasSpin, Intra-Lock, Boca Raton, FL). L-PRF membranes were obtained from XPression fabrication kit (Biohorizons Implant Systems, Inc., AL, USA). A split mouth approach was adopted with the first molar mesial and distal socket defects treated in an interpolated fashion of the following study groups: 1) Empty socket (negative control); 2) OSS filled defect 3) L-PRF membrane; and 4) Mix of Bio-Oss® with L-PRF. After six weeks, samples were harvested, histologically processed, and evaluated for bone area fraction occupancy (BAFO), vertical/horizontal ridge dimensions (VRD and HRD, respectively), and area of coronal soft tissue infiltration. RESULTS:BAFO was statistically lower for the control group in comparison to all treatment groups. Defects treated with Bio-Oss® were not statistically different then defects treated solely with L-PRF. Collapsed across all groups, L-PRF exhibited higher degrees of BAFO than groups without L-PRF. Defects filled with Bio-Oss® and Bio-Oss® with L-PRF demonstrated greater maintenance of VRD relative to the control group. Collapsed across all groups, Bio-Oss® maintained the VRD and resulted in less area of coronal soft tissue infiltration compared to the empty defect. Soft tissue infiltration observed at the coronal area was not statistically different among defects filled with L-PRF, Bio-Oss®, and Bio-Oss® with L-PRF. CONCLUSIONS:Inclusion of L-PRF to particulate xenograft did not promote additional bone heading at 6 weeks in vivo. However, we noted that L-PRF alone promoted alveolar socket regeneration to levels comparable to particulate xenografts, suggesting its potential utilization for socket preservation.

PURPOSE/OBJECTIVE:To evaluate the effect of composition, fabrication mode, and thermal cycling on the mechanical properties of different polymeric systems used for temporary dental prostheses. MATERIALS AND METHODS/METHODS:Standard bar-shaped specimens (25 × 2 × 2 mm) were fabricated of six polymeric systems of varying compositions and fabrication modes (n = 10/group): conventional PMMA (Alike, GC) - group CGC; conventional PMMA (Dêncor, Clássico) - group CD; bis-acryl (Tempsmart, GC) - group BGC; bis-acryl (Yprov, Yller) - group BY; milled PMMA (TelioCAD, Ivoclar) - group MI; 3D printed bis-acryl - (Cosmos Temp, Yller) group PY. Half of the specimens were subjected to 5000 thermal cycles (5 °C to 55 °C). Three-point bending tests were performed using a universal testing machine with a crosshead speed set to 0.5 mm/min. Flexural strength and elastic modulus were calculated from the collected data. FTIR spectra were recorded pre and post curing and after thermal cycling to evaluate material composition and degree of conversion. Energy-dispersive spectroscopy (EDS) and scanning electron microscope (SEM) were utilized to examine the composition and micromorphology of the systems, respectively. Data were analyzed using two-analysis of variance and Tukey tests (α = 0.05). RESULTS:FTIR spectra indicated that BGC, BY and PY groups corresponded to urethane dimethacrylate systems (bis-acryl), while CGC, CD, and MI groups corresponded to monomethacrylate systems, polymethyl methacrylate (PMMA). Bis-acryl BGC system yeilded the highest flexural strength (80 MPa), followed by the milled PMMA MI system (71 MPa), both statistically significant different relative to other groups. Bis-acryl BY exhibited the lowest flexural strength (27 MPa). Thermocycling significantly increased the flexural strength of all polymeric systems (∼10-15 MPa), except for the 3D-printed PY group. Bis-acryl BGC (1.89 GPa) and conventional PMMA CGC (1.66 GPa) groups exhibited the highest elastic modulus, followed by milled PMMA MI group (1.51 GPa) and conventional PMMA CD (1.45 GPa) systems, with significant difference detected between BGC group and MI and CD groups. The 3D printed PY (0.78 GPa) and bis-acryl BY (0.47 GPa) systems presented the lowest elastic modulus. Thermocycling did not have a significant influence on the elastic modulus. FTIR spectra indicate water sorption and release of unreacted monomers as well as increased degree of conversion (∼5-12%) after thermal cycling. CONCLUSION/CONCLUSIONS:Composition and fabrication mode and thermal cycling significantly affected the mechanical properties of polymeric systems used for temporary dental prostheses.

The present study aimed to evaluate the effect of parathormone (PTH) administered directly to the implant's surface prior to insertion, using a large translational animal model. Sixty titanium implants were divided into four groups: (i) Collagen, control group, where implants were coated with Type-I Bovine-collagen, and three experimental groups, where implants received varying doses of PTH: (ii) 12.5, (iii) 25, and (iv) 50 μg, prior to placement. Fifteen female sheep (~2 years old, weighing ~65 kg) received four implants in an interpolated fashion in C3, C4 or C5 vertebral bodies. After 3-, 6- and 12-weeks, samples were harvested, histologically processed, qualitatively and quantitatively assessed for bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). BIC yielded lower values at 6-weeks for 50 μg relative to the control group, with no significant differences, when compared to the 12.5- and 25-μg. No significant differences were detected at 6-weeks between collagen, 12.5- and 25-μg groups. At 3- and 12-weeks, no differences were detected for BIC among PTH groups. With respect to BAFO, no significant differences were observed between the control and experimental groups independent of PTH concentration and time in vivo. Qualitative observations at 3-weeks indicated the presence of a more mature bone near the implant's surface with the application of PTH, however, no significant differences in new bone formation or healing patterns were observed at 6- and 12-weeks. Single local application of different concentrations of PTH on titanium implant's surface did not influence the osseointegration at any time-point evaluation in low-density bone.

It is well known that Semaphorin 4D (Sema4D) inhibits IGF-1-mediated osteogenesis by binding with PlexinB1 expressed on osteoblasts. However, its elevated level in the gingival crevice fluid of periodontitis patients and the broader scope of its activities in the context of potential upregulation of osteoclast-mediated periodontal bone-resorption suggest the need for further investigation of this multifaceted molecule. In short, the pathophysiological role of Sema4D in periodontitis requires further study. Accordingly, attachment of the ligature to the maxillary molar of mice for 7 days induced alveolar bone-resorption accompanied by locally elevated, soluble Sema4D (sSema4D), TNF-α and RANKL. Removal of the ligature induced spontaneous bone regeneration during the following 14 days, which was significantly promoted by anti-Sema4D-mAb administration. Anti-Sema4D-mAb was also suppressed in vitro osteoclastogenesis and pit formation by RANKL-stimulated BMMCs. While anti-Sema4D-mAb downmodulated the bone-resorption induced in mouse periodontitis, it neither affected local production of TNF-α and RANKL nor systemic skeletal bone remodeling. RANKL-induced osteoclastogenesis and resorptive activity were also suppressed by blocking of CD72, but not Plexin B2, suggesting that sSema4D released by osteoclasts promotes osteoclastogenesis via ligation to CD72 receptor. Overall, our data indicated that ssSema4D released by osteoclasts may play a dual function by decreasing bone formation, while upregulating bone-resorption.

Skeletal conditions represent a considerable challenge to health systems globally. Barriers to effective therapeutic development include a lack of accurate preclinical tissue and disease models. Most recently, work was attempted to present a novel whole organ approach to modeling human bone and cartilage tissues. These self-assembling skeletal organoids mimic the cellular milieu and extracellular organization present in native tissues. Bone organoids demonstrated osteogenesis and micro vessel formation, and cartilage organoids showed evidence of cartilage development and maturation. Skeletal organoids derived from both bone and cartilage tissues yielded spontaneous polarization of their cartilaginous and bone components. Using these hybrid skeletal organoids, we successfully generated "mini joint" cultures, which we used to model inflammatory disease and test Adenosine (A_2A ) receptor agonists as a therapeutic agent. The work and respective results indicated that skeletal organoids can be an effective biological model for tissue development and disease as well as to test therapeutic agents.

BACKGROUND:The aim of the present study was to evaluate the effect of different concentrations of growth hormone (GH) on endosteal implant's surface at the early stages of osseointegration. MATERIAL AND METHODS/METHODS:Sixty tapered acid-etched titanium implants were divided into four groups: i) Collagen, used as a control group; and three experimental groups, where after collagen coating, GH was administered directly to the surface in varying concentrations: ii) 0.265 mg, iii) 0.53 mg, and iv) 1 mg. Implants were placed in an interpolated fashion in the anterior flange of C3, C4 or C5 of 15 sheep with minimum distance of 6 mm between implants. After 3-, 6- and 12-weeks of healing samples were harvested, histologically processed, qualitatively and quantitatively assessed for bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). RESULTS:Statistical analysis as a function of time in vivo and coating resulted in no significant differences for BIC and BAFO at any evaluation time point. Histological evaluation demonstrated similar osseointegration features for all groups with woven bone formation at 3 weeks and progressive replacement of woven for lamellar bone in close contact with the implant surface and within the implant's threads. CONCLUSIONS:A single local application of growth hormone to the surface of titanium implants did not yield improved implant osseointegration independent of healing time.

HYPOTHESIS/OBJECTIVE:Injuries requiring resection of tissue followed by autogenous bone transfer may be prone to infection by Staphylococcus aureus, impeding recovery and increasing medical costs. For critical sized defects, the common approach to reconstruction is a tissue transfer procedure but is subject to limitations (e.g., donor site morbidity, cost, operating time). Utilizing beta tricalcium phosphate (β-TCP) as bone grafting material augmented with silver (Ag), a custom graft may be 3D printed to overcome limitations and minimize potential infections. EXPERIMENTS/METHODS:) groups followed by electron microscopy, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) to gather information of chemical and physical properties. Preliminary biocompatibility and bactericidal capacity of the scaffolds were tested using human osteoprogenitor (hOP) cells and methicillin-sensitive S. aureus strain, respectively. RESULTS:groups, whereas electron microscopy showed a decrease in Ca and an increase in Ag ions, decreasing Ca/P ratio with increasing surfactant concentrations. PrestoBlue assays yielded an increase in fluorescence cell counts among experimental groups with lower concentrations of Ag characterized by their characteristic trapezoidal shape whereas cytotoxicity was observed at higher concentrations. Similar observations were made with alkaline phosphatase assays. Antimicrobial evaluation showed reduced colony-forming units (CFU) among all experimental groups when compared to 100% β-TCP. β-TCP scaffolds augmented with Ag ions facilitate antibacterial effects while promoting osteoblast adhesion and proliferation.

BACKGROUND/UNASSIGNED:The use of low-temperature plasma (LTP) is a novel approach to treating peri-implantitis. LTP disrupts the biofilm while conditioning the surrounding host environment for bone growth around the infected implant. The main objective of this study was to evaluate the antimicrobial properties of LTP on newly formed (24 h), intermediate (3 days), and mature (7 days) peri-implant-related biofilms formed on titanium surfaces. METHODS/UNASSIGNED: RESULTS/UNASSIGNED:≤ 0.016), and CLSM corroborated these results. CONCLUSION/UNASSIGNED:.

Glass ceramics' fractures in zirconia fixed dental prosthesis (FDP) remains a clinical challenge since it has higher fracture rates than the gold standard, metal ceramic FDP. Nanoindentation has been shown a reliable tool to determine residual stress of ceramic systems, which can ultimately correlate to failure-proneness.