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Three dimensionally printed bioactive ceramic scaffold osseoconduction across critical-sized mandibular defects

Lopez, Christopher D; Diaz-Siso, J Rodrigo; Witek, Lukasz; Bekisz, Jonathan M; Cronstein, Bruce N; Torroni, Andrea; Flores, Roberto L; Rodriguez, Eduardo D; Coelho, Paulo G
BACKGROUND:Vascularized bone tissue transfer, commonly used to reconstruct large mandibular defects, is challenged by long operative times, extended hospital stay, donor-site morbidity, and resulting health care. 3D-printed osseoconductive tissue-engineered scaffolds may provide an alternative solution for reconstruction of significant mandibular defects. This pilot study presents a novel 3D-printed bioactive ceramic scaffold with osseoconductive properties to treat segmental mandibular defects in a rabbit model. METHODS:Full-thickness mandibulectomy defects (12 mm) were created at the mandibular body of eight adult rabbits and replaced by 3D-printed ceramic scaffold made of 100% β-tricalcium phosphate, fit to defect based on computed tomography imaging. After 8 weeks, animals were euthanized, the mandibles were retrieved, and bone regeneration was assessed. Bone growth was qualitatively assessed with histology and backscatter scanning electron microscopy, quantified both histologically and with micro computed tomography and advanced 3D image reconstruction software, and compared to unoperated mandible sections (UMSs). RESULTS:Histology quantified scaffold with newly formed bone area occupancy at 54.3 ± 11.7%, compared to UMS baseline bone area occupancy at 55.8 ± 4.4%, and bone area occupancy as a function of scaffold free space at 52.8 ± 13.9%. 3D volume occupancy quantified newly formed bone volume occupancy was 36.3 ± 5.9%, compared to UMS baseline bone volume occupancy at 33.4 ± 3.8%, and bone volume occupancy as a function of scaffold free space at 38.0 ± 15.4%. CONCLUSIONS:3D-printed bioactive ceramic scaffolds can restore critical mandibular segmental defects to levels similar to native bone after 8 weeks in an adult rabbit, critical sized, mandibular defect model.
PMCID:5812371
PMID: 29433862
ISSN: 1095-8673
CID: 2956942

Internet-Based Digital Simulation for Cleft Surgery Education: A 5-Year Assessment of Demographics, Usage, and Global Effect

Kantar, Rami S; Plana, Natalie M; Cutting, Court B; Diaz-Siso, Jesus Rodrigo; Flores, Roberto L
BACKGROUND:In October 2012, a freely available, internet-based cleft simulator was created in partnership between academic, nonprofit, and industry sectors. The purpose of this educational resource was to address global disparities in cleft surgery education. This report assesses demographics, usage, and global effect of our simulator, in its fifth year since inception. OBJECTIVE:Evaluate the global effect, usage, and demographics of an internet-based educational digital simulation cleft surgery software. SETTING AND PARTICIPANTS/METHODS:Simulator modules, available in five languages demonstrate surgical anatomy, markings, detailed procedures, and intraoperative footage to supplement digital animation. Available data regarding number of users, sessions, countries reached, and content access were recorded. Surveys evaluating the demographic characteristics of registered users and simulator use were collected by direct e-mail. RESULTS:The total number of simulator new and active users reached 2865 and 4086 in June 2017, respectively. By June 2017, users from 136 countries had accessed the simulator. From 2015 to 2017, the number of sessions was 11,176 with a monthly average of 399.0 ± 190.0. Developing countries accounted for 35% of sessions and the average session duration was 9.0 ± 7.3 minutes. This yields a total simulator screen time of 100,584 minutes (1676 hours). Most survey respondents were surgeons or trainees (87%) specializing in plastic, maxillofacial, or general surgery (89%). Most users found the simulator to be useful (88%), at least equivalent or more useful than other resources (83%), and used it for teaching (58%). CONCLUSIONS:Our internet-based interactive cleft surgery platform reaches its intended target audience, is not restricted by socioeconomic barriers to access, and is judged to be useful by surgeons. More than 4000 active users have been reached since inception. The total screen time over approximately 2 years exceeded 1600 hours. This suggests that future surgical simulators of this kind may be sustainable by stakeholders interested in reaching this target audience.
PMID: 29396278
ISSN: 1878-7452
CID: 2947952

Histo-morphologic characteristics of intra-osseous implants of WE43 Mg alloys with and without heat treatment in an in vivo cranial bone sheep model

Torroni, Andrea; Xiang, Chongchen; Witek, Lukasz; Rodriguez, Eduardo D; Flores, Roberto L; Gupta, Nikhil; Coelho, Paulo G
WE43 Mg alloy, composed of Mg, Yttrium, Rare Earth elements, and Zirconium, has proved to be a suitable candidate for production of resorbable osteosynthesis implants in both clinical and experimental settings. In a previous study we tested biocompatibility and degradation properties of untreated (as-cast) and artificially aged (T-5) WE43 Mg-alloys as subperiosteal implants on a maxillofacial sheep model. Both the alloy compositions showed excellent biocompatibility, however, with respect to degradation rate, the as-cast form showed increased degradability compared with the T-5. In the present study, we tested the same alloy composition (i.e. as-cast and T-5) to assess their biological behavior and degradation pattern when implanted as endosteal implants on a calvarial bone sheep model. Six implants in form of cylindrical discs were tested in 6 sheep, one per composition of each disc was placed in two monocortical cranial defect created with high speed trephine bur in the parietal bone. After euthanasia at 6 weeks histomorphological analysis of the bone/implant specimens was performed. WE43-as cast showed higher degradation rate, increased bone remodeling, gas pockets formation and osteolysis compared with the T5 alloy. WE43-T5 showed greater bone/implant interface stability, and seemed to be more suitable for fabrication of endosteal bone screws.
PMID: 29398208
ISSN: 1878-4119
CID: 2947982

The First Year of Global Cleft Surgery Education Through Digital Simulation: A Proof of Concept

Plana, Natalie M; Diaz-Siso, J Rodrigo; Culnan, Derek M; Cutting, Court B; Flores, Roberto L
INTRODUCTION/BACKGROUND:Parallel to worldwide disparities in patient access to health care, the operative opportunities of surgical trainees are increasingly restricted across the globe. Efforts have been directed toward enhancing surgical education outside the operating room and reducing the wide variability in global trainee operative experience. However, high costs and other logistical concerns may limit the reproducibility and sustainability of nonoperative surgical education resources. METHODS:A partnership between the academic, nonprofit, and industry sectors resulted in the development of an online virtual surgical simulator for cleft repair. First year global access patterns were observed. RESULTS:The simulator is freely accessible online and includes 5 normal and pathologic anatomy modules, 5 modules demonstrating surgical markings, and 7 step-by-step procedural modules. Procedural modules include high-definition intraoperative footage to supplement the virtual animation in addition to include multiple-choice test questions. In its first year, the simulator was accessed by 849 novel users from 78 countries; 70% of users accessed the simulator from a developing nation. CONCLUSION/CONCLUSIONS:The Internet shows promise as a platform for surgical education and may help address restrictions and reduce disparities in surgical training. The virtual surgical simulator presented may serve as the foundation for the development of a global curriculum in cleft repair.
PMID: 29406778
ISSN: 1545-1569
CID: 2948072

The Effect of Nasoalveolar Molding on Nasal Airway Anatomy: A 9-Year Follow-up of Patients With Unilateral Cleft Lip and Palate

Massie, Jonathan P; Bruckman, Karl; Rifkin, William J; Runyan, Christopher M; Shetye, Pradip R; Grayson, Barry; Flores, Roberto L
OBJECTIVE:To determine the effects of nasoalveolar molding (NAM) on nasal airway architecture. DESIGN/METHODS:Retrospective case-control study of patients with unilateral cleft lip treated with NAM vs without NAM. SETTING/METHODS:Tertiary referral center specializing in cleft and craniofacial care. Patients, Participants, and Interventions: Thirty-six patients with complete unilateral cleft lip and alveolus: 19 with NAM therapy and 17 without NAM therapy. MAIN OUTCOME MEASURES/METHODS:Cone beam computed tomography (CBCT) scans were compared in multiple coronal sections and were evaluated for linear and angular septal deviation, inferior turbinate hypertrophy, and linear and 2-dimensional airway area. RESULTS:There were no significant differences in linear or angular septal deviation, inferior turbinate area, linear stenosis, or airway area between NAM- and non-NAM-treated patients. CONCLUSIONS:NAM effectively molds the external nasal cartilage and structures but may have limited effects on internal nasal structures.
PMID: 29356619
ISSN: 1545-1569
CID: 2929392

Dipyridamole enhances osteogenesis of three-dimensionally printed bioactive ceramic scaffolds in calvarial defects

Bekisz, Jonathan M; Flores, Roberto L; Witek, Lukasz; Lopez, Christopher D; Runyan, Christopher M; Torroni, Andrea; Cronstein, Bruce N; Coelho, Paulo G
PURPOSE/OBJECTIVE:The objective of this study was to test the osteogenic capacity of dipyridamole-loaded, three-dimensionally printed, bioactive ceramic (3DPBC) scaffolds using a translational, skeletally mature, large-animal calvarial defect model. MATERIALS AND METHODS/METHODS:Custom 3DPBC scaffolds designed to present lattice-based porosity only towards the dural surface were either coated with collagen (control) or coated with collagen and immersed in a 100 μM concentration dipyridamole (DIPY) solution. Sheep (n = 5) were subjected to 2 ipsilateral trephine-induced (11-mm diameter) calvarial defects. Either a control or a DIPY scaffold was placed in each defect, and the surgery was repeated on the contralateral side 3 weeks later. Following sacrifice, defects were evaluated through microcomputed tomography and histologic analysis for bone, scaffold, and soft tissue quantification throughout the defect. Parametric and non-parametric methods were used to determine statistical significance based on data distribution. RESULTS:No exuberant or ectopic bone formation was observed, and no histologic evidence of inflammation was noted within the defects. Osteogenesis was higher in DIPY-coated scaffolds compared to controls at 3 weeks (p = 0.013) and 6 weeks (p = 0.046) in vivo. When bone formation was evaluated as a function of defect radius, average bone formation was higher for DIPY relative to control scaffolds at both time points (significant at defect central regions at 3 weeks and at margins at 6 weeks, p = 0.046 and p = 0.031, respectively). CONCLUSION/CONCLUSIONS:Dipyridamole significantly improves the calvarial bone regeneration capacity of 3DPBC scaffolds. The most significant difference in bone regeneration was observed centrally within the interface between the 3DPBC scaffold and the dura mater.
PMCID:5803375
PMID: 29292126
ISSN: 1878-4119
CID: 2899422

A Review of Randomized Controlled Trials in Cleft and Craniofacial Surgery

Bekisz, Jonathan M; Fryml, Elise; Flores, Roberto L
This study presents a systematic review of randomized controlled trials (RCTs) in cleft and craniofacial surgery. All studies reporting on RCTs in cleft and craniofacial surgery were identified on PubMed using the search terms "cleft," "velopharyngeal insufficiency," "velopharyngeal dysfunction," "nasoalveolar molding," "gingivoperiosteoplasty," "Pierre Robin sequence," "craniofacial," "craniosynostosis," "craniofacial microsomia," "hemifacial microsomia," "hypertelorism," "Le Fort," "monobloc," "distraction osteogenesis," "Treacher Collins," and "Goldenhar." Studies were excluded if they were not randomized, did not focus primarily on topics related to cleft or craniofacial surgery, included repeat publications of data, or were unavailable in English. Studies were evaluated on demographic and bibliometric data, study size, specific area of focus, and findings reported. Four hundred forty-seven unique studies were identified. One hundred eighty-three papers met inclusion criteria (115 cleft lip and palate, 65 craniofacial, and 3 spanning both disciplines). Sixty-six (36%) were dedicated to topics related to surgical techniques. There were no studies comparing current cleft lip or soft palate repair techniques and no studies on cleft rhinoplasty. The most frequently reported surgical topic was cleft palate. There were several studies on orthognathic techniques which compared distraction osteogenesis to traditional advancement. Most craniofacial operations, such as cranial vault remodeling and frontofacial advancement/distraction, were not represented. Several standard operations in cleft and craniofacial surgery are not supported by Level I evidence from randomized controlled trials. Our community should consider methods by which more RCTs can be performed, or redefine the acceptable standards of evidence to guide our clinical decisions.
PMID: 29084117
ISSN: 1536-3732
CID: 2765962

Distraction of the mandible

Chapter by: McCarthy, Joseph G.; Flores, Roberto L.
in: Craniofacial Distraction by
[S.l.] : Springer International Publishing, 2017
pp. 45-88
ISBN: 9783319525624
CID: 2796072

Distraction osteogenesis: Biologic and biomechanical principles

Chapter by: Runyan, Christopher M.; Flores, Roberto L.; McCarthy, Joseph G.
in: Craniofacial Distraction by
[S.l.] : Springer International Publishing, 2017
pp. 11-43
ISBN: 9783319525624
CID: 2796112

Distraction of the midface: Le fort III and monobloc

Chapter by: McCarthy, Joseph G.; Flores, Roberto L.
in: Craniofacial Distraction by
[S.l.] : Springer International Publishing, 2017
pp. 135-175
ISBN: 9783319525624
CID: 2796122