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496


Locally Secreted Semaphorin 4D Is Engaged in Both Pathogenic Bone Resorption and Retarded Bone Regeneration in a Ligature-Induced Mouse Model of Periodontitis

Ishii, Takenobu; Ruiz-Torruella, Montserrat; Yamamoto, Kenta; Yamaguchi, Tsuguno; Heidari, Alireza; Pierrelus, Roodelyne; Leon, Elizabeth; Shindo, Satoru; Rawas-Qalaji, Mohamad; Pastore, Maria Rita; Ikeda, Atsushi; Nakamura, Shin; Mawardi, Hani; Kandalam, Umadevi; Hardigan, Patrick; Witek, Lukasz; Coelho, Paulo G; Kawai, Toshihisa
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.
PMID: 35628440
ISSN: 1422-0067
CID: 5236292

Self-assembling human skeletal organoids for disease modeling and drug testing

Abraham, Diana M; Herman, Calvin; Witek, Lukasz; Cronstein, Bruce N; Flores, Roberto L; Coelho, Paulo G
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 (A2A ) 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.
PMID: 34837719
ISSN: 1552-4981
CID: 5063982

Effects of a local single dose administration of growth hormone on the osseointegration of titanium implants

Grossi, J-R; Parra, M; Benalcázar-Jalkh, E-B; Giovanini, A-F; Zielak, J-C; Sebstiani, A-M; Gonzaga, C-C; Coelho, P-G; Witek, L; Deliberador, T-M
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.
PMID: 35218646
ISSN: 1698-6946
CID: 5172642

Physiochemical and bactericidal activity evaluation: Silver-augmented 3D-printed scaffolds-An in vitro study

Nayak, Vasudev Vivekanand; Tovar, Nick; Hacquebord, Jacques Henri; Duarte, Simone; Panariello, Beatriz H D; Tonon, Caroline; Atria, Pablo J; Coelho, Paulo G; Witek, Lukasz
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.
PMID: 34196107
ISSN: 1552-4981
CID: 4932082

The presence of 3D printing in orthopedics: A clinical and material review [Review]

Colon, Ricardo Rodriguez; Nayak, Vasudev Vivekanand; Parente, Paulo E. L.; Leucht, Philipp; Tovar, Nick; Lin, Charles C.; Rezzadeh, Kevin; Hacquebord, Jacques H.; Coelho, Paulo G.; Witek, Lukasz
ISI:000808151100001
ISSN: 0736-0266
CID: 5302692

Low-Temperature Plasma Short Exposure to Decontaminate Peri-Implantitis-Related Multispecies Biofilms on Titanium Surfaces In Vitro

Panariello, Beatriz H D; Mody, Drashty P; Eckert, George J; Witek, Lukasz; Coelho, Paulo G; Duarte, Simone
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:.
PMCID:10205409
PMID: 37228507
ISSN: 2314-6141
CID: 5503792

Tissue Engineering Strategies for Craniomaxillofacial Surgery: Current Trends in 3D-Printed Bioactive Ceramic Scaffolds

Chapter by: Witek, Lukasz; Nayak, Vasudev Vivekanand; Runyan, Christopher M; Tovar, Nick; Elhage, Sharbel; Melville, James C; Young, Simon; Kim, David H; Cronstein, Bruce N; Flores, Roberto L; Coelho, Paulo G
in: Innovative Bioceramics in Translational Medicine II by Choi, Andy H; Ben-Nissan, Besim [Eds]
Cham : Springer, 2022
pp. 55-74
ISBN: 978-981-16-7438-9
CID: 5457532

The Influence of Surface Treatment on Osseointegration of Endosteal Implants Presenting Decompressing Vertical Chambers: An In Vivo Study in Sheep

Parra, Marcelo; Benalcázar Jalkh, Ernesto B; Tovar, Nick; Torroni, Andrea; Badalov, Rafael M; Bonfante, Estevam A; Nayak, Vasudev; Castellano, Arthur; Coelho, Paulo G; Witek, Lukasz
PURPOSE/OBJECTIVE:blasting + maleic + HCl) in a large translational animal model at 3 and 6 weeks in vivo. MATERIALS AND METHODS/METHODS:Nine female sheep were used, and 72 implants with trapezoidal threads and decompressing vertical chambers of 0.6 mm in diameter and 0.2 mm in depth were placed in the ilium crest. After 3 and 6 weeks, the animals were euthanized, and biomechanical and histomophometric analyses were performed. RESULTS:Survey histologic evaluation indicated intimate contact between the bone and the implants independent of surface treatment at both times in vivo. Bone formation at both time points depicted an intramembranous-type healing pattern between the implant threads. The mean removal torque values for all groups showed a relative increase in removal torque from 3 to 6 weeks. In terms of bone area fraction occupancy analysis, significant differences were found at 6 weeks between surface treatments (P = .046), where the experimental surface yielded higher degrees of bone area fraction occupancy. CONCLUSION/CONCLUSIONS:Conical implants with decompressing vertical chambers between threads presented similar osseointegration parameters regarding bone-toimplant contact and torque-out test values irrespective of surface treatment. However, shifting from a minimally rough to a moderately rough surface (experimental surface with supplemental acid-etching) resulted in significantly improved bone area fraction occupancy at 6 weeks.
PMID: 36170307
ISSN: 1942-4434
CID: 5439392

Residual stress estimated by nanoindentation in pontics and abutments of veneered zirconia fixed dental prostheses

Fardin, Vinicius Pavesi; Bonfante, Gerson; Coelho, Paulo G; Bergamo, Edmara T P; Bordin, Dimorvan; Janal, Malvin N; Tovar, Nick; Witek, Lukasz; Bonfante, Estevam A
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.
PMCID:9041093
PMID: 35476114
ISSN: 1678-7765
CID: 5206382

Effect of different tightening protocols on the probability of survival of screw-retained implant-supported crowns

Fardin, Vinicius P; Bergamo, Edmara T P; Bordin, Dimorvan; Hirata, Ronaldo; Bonfante, Estevam A; Bonfante, Gerson; Coelho, Paulo G
PURPOSE/OBJECTIVE:This study evaluated the effect of different tightening protocols on the probability of survival of screw-retained implant-supported anterior crowns. MATERIALS AND METHODS/METHODS:Seventy-two implants with internal conical connections (4.0 × 10mm, Ti-6Al-4V, Colosso, Emfils) were divided into four groups (n = 18 each): 1) Manufacturer's recommendations torque (25 N.cm for abutment's screw and 30 N.cm for crown's screw) (MaT); 2) Retightening after 10 min (ReT); 3) Torque 16% below recommended to simulate an uncalibrated wrench (AgT), and; 4) Temporary crown simulation (TeT), where crowns were torqued to 13 N.cm to simulate manual tightening, subjected to 11,200 cycles to simulate temporary crown treatment time (190 N), and then retightened to manufacturer torque (TeT). All specimens were subjected to cyclic fatigue in distilled water with a load of 190 N until 250,000 cycles or failure. The probability of survival (reliability) to complete a mission of 50,000 cycles was calculated and plotted using the Weibull 2-Parameter analysis. Weibull modulus and number of cycles at which 62.3% of the specimens would fail were also calculated and plotted. The failure mode was characterized in stereo and scanning electron microscopes (SEM). RESULTS:The probability of survival was 69.3% for MaT, 70% for ReT, 54.8% for AgT, and 40.3% for TeT, all with no statistically significant difference. Weibull modulus was approximately 1.0 for all groups. The characteristic number of cycles for failure was 105,000 cycles for MaT, 123,000 for ReT, 82,000 cycles for AgT, and 54,900 cycles for TeT, with no significant difference between groups. The chief failure mode for MaT, ReT, AgT groups was crown screw fracture, whereas abutment screw fracture was the chief failure mode for the TeT group. CONCLUSION/CONCLUSIONS:Tightening protocol did not influence the probability of survival of the screw-retained anterior crowns supported by internal conical implants (Ti-6Al-4V, Colosso, Emfils).
PMID: 34875501
ISSN: 1878-0180
CID: 5099562