Faculty Bibliography

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.

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.

OBJECTIVES/OBJECTIVE:To characterize the mechanical and biological properties of three commercially available resins, which are currently used for provisional restorations and to compare them to an experimental resin intended for definitive fixed dental prostheses. MATERIALS AND METHODS/METHODS:Three commercially available resins: Crowntec (CT, Saremco), Temporary C&B (FL, Formlabs), C&B MFH (ND, Nextdent), and the experimental resin: Permanent Bridge (PB, Saremco) were printed and subjected to biaxial flexural strength test, finite element analysis, Weibull analysis, scanning electron microscopy, cell proliferation, immunohistochemistry and cytotoxicity assays. Samples from CT, PB, and ND were provided directly from the manufacturers ensuring ideal workflow. FL was printed using the workflow as recommended by the manufacturer, using a Formlabs 2 printer and their post-processing units Form Wash and Form Cure. RESULTS:From the tested resins, PB yielded the best overall results in terms of mechanical properties. Cell proliferation and cytotoxicity did not show any significant differences among materials. PB showed higher values for probability of survival predictions (35%) when subjected to 250 MPa loads, whereas the other materials did not reach 10%. SIGNIFICANCE/CONCLUSIONS:Despite mechanical differences between the evaluated materials, the outcomes suggest that 3D printed provisional resins may be used in clinical settings, following the manufacturers indications. New materials intended for long-term use, such as the PB resin, yielded higher mechanical properties compared to the other materials. Alternative printing and post-processing methods have not yet been evaluated and should be avoided until further literature is available. CLINICAL SIGNIFICANCE/CONCLUSIONS:3D printed resins for provisional restorations have become popular with the emergence of new technologies. In this study, we evaluated three different commercially available resins for provisional restorations and one new experimental resin. The results from this study indicate that commercially available resins could be used in clinical settings under certain conditions and limited periods of time. Following the manufacturers protocols is of paramount importance to not compromise these properties.

BACKGROUND:Computerized surgical planning (CSP) in osseous reconstruction of head and neck cancer defects has become a mainstay of treatment. However, the consequences of CSP-designed titanium plating systems on planning adjuvant radiation remains unclear. METHODS:Two patients underwent head and neck cancer resection and maxillomandibular free fibula flap reconstruction with CSP-designed plates and immediate placement of osseointegrated dental implants. Surgical treatment was followed by adjuvant intensity modulated radiation therapy (IMRT). RESULTS:Both patients developed osteoradionecrosis (ORN), and one patient had local recurrence. The locations of disease occurred at the areas of highest titanium plate burden, possibly attributed to IMRT dosing inaccuracy caused by the CSP-designed plating system. CONCLUSION/CONCLUSIONS:Despite proven benefits of CSP-designed plates in osseous free flap reconstruction, there may be an underreported risk to adjuvant IMRT treatment planning leading to ORN and/or local recurrence. Future study should investigate alternative plating methods and materials to mitigate this debilitating outcome.

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.

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.

Bone defects are often linked to congenital disorders, high impact traumas, tumors or oncological resections. Potential treatment options include autografts, allografts, or synthetic grafts, such as bioactive ceramic-based materials which have been successfully utilized in an effort to regenerate bone. β-tricalcium phosphate (β-TCP), is a commonly utilized bioactive ceramic for regenerative purposes with favorable osteoconductive properties. Alternatively, Synthetic Bone Mineral (SBM) has been previously utilized in in vivo experiments as a supplement for bone loss treatment. As a potential alternative to β-TCP, it is also a bioactive ceramic, which consists of a carbonate hydroxyapatite with ionic substitutions such as F^−, Zn²⁺ and Mg²⁺. The objective of this work was to characterize the physiochemical properties of the colloidal gel obtained from a formulation of SBM and compare the properties directly to β-TCP. Mechanical properties were evaluated for both materials in bulk, using Biaxial Flexural Strength tests. Scanning electron microscopy and micro-computed tomography were utilized to explore the structure of the bulk material and the three dimensionally (3D) printed scaffolds. Inductive coupled plasma (ICP), X-ray diffraction (XRD), and Fourier transform infrared spectrometry (FT-IR), were utilized to determine the calcium-phosphorous ratio (Ca:P), quantitative analysis of crystalline phases, and functional groups, respectively. Thermogravimetric analysis (TGA) was used to quantify the weight percent of water, organic components, carbonate and mineral in the SBM colloidal gel. Flexural strength of SBM discs sintered at 700°C were statistically analogous to β-TCP sintered at 900°C. The Ca:P ratio of the sintered SBM was found to be 1.47 ± 0.04, statistically different from β-TCP sintered at higher temperatures. The carbonate content of the SBM was determined to be ~2.8% ± 0.9. The novel SBM colloidal gel has hence been characterized chemically and physically for its potential use in 3D printing grafts to repair critical sized bone defects.

BACKGROUND:β-Tricalcium phosphate (β-TCP) is one of the most common synthetic bone grafting materials utilized in craniofacial reconstruction; however, it is limited by a slow degradation rate. The aim of this study was to leverage 3-dimensional (3D) printing in an effort to accelerate the degradation kinetics of β-TCP. METHODS:Twenty-two 1-month-old New Zealand white rabbits underwent creation of calvarial and alveolar defects, repaired with 3D-printed β-TCP scaffolds coated with 1000 μM of osteogenic agent dipyridamole. Rabbits were euthanized after 2, 6, and 18 months after surgical intervention. Bone regeneration, scaffold degradation, and bone mechanical properties were quantified. RESULTS:Histological analysis confirmed the generation of vascularized and organized bone. Microcomputed tomography analysis from 2 to 18 months demonstrated decreased scaffold volume within calvarial (23.6% ± 2.5%, 5.1% ± 2.2%; P < 0.001) and alveolar (21.5% ± 2.2%, 0.2% ± 1.9%; P < 0.001) defects, with degradation rates of 54.6%/year and 90.5%/year, respectively. Scaffold-inducted bone generation within the defect was volumetrically similar to native bone in the calvarium (55.7% ± 6.9% vs 46.7% ± 6.8%; P = 0.064) and alveolus (31.4% ± 7.1% vs 33.8% ± 3.7%; P = 0.337). Mechanical properties between regenerated and native bone were similar. CONCLUSIONS:Our study demonstrates an improved degradation profile and replacement of absorbed β-TCP with vascularized, organized bone through 3D printing and addition of an osteogenic agent. This novel additive manufacturing and tissue engineering protocol has implications to the future of craniofacial skeletal reconstruction as a safe and efficacious bone tissue engineering method.