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Long-term outcomes of 3D-printed bioactive ceramic scaffolds for regeneration of the pediatric skeleton
Chapter by: Wang, M. M.; Rodriguez Colon, R.; Kurgansky, G. D.; Witek, L.; Torroni, A.; Cronstein, B. N.; Flores, R. L.; Coelho, P. G.
in: Transactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium by
[S.l. : s.n.], 2019
pp. 138-?
ISBN: 9781510883901
CID: 3913082
3D Printing and Adenosine Receptor Activation for Craniomaxillofacial Regeneration
Chapter by: Lopez, Christopher D; Witek, Lukasz; Flores, Roberto L; Torroni, Andrea; Rodriguez, Eduardo D; Cronstein, Bruce N; Coelho, Paulo G
in: Regenerative strategies for maxillary and mandibular reconstruction : a practical guide by Melville, James C; et al [Eds]
Cham, Switzerland : Springer, [2019]
pp. 255-267
ISBN: 9783319936673
CID: 5457522
Haptic, Physical, and Web-Based Simulators: Are They Underused in Maxillofacial Surgery Training?
Maliha, Samantha G; Diaz-Siso, J Rodrigo; Plana, Natalie M; Torroni, Andrea; Flores, Roberto L
PURPOSE/OBJECTIVE:Surgical residencies have increasingly incorporated both digital and mannequin simulation into their training programs. The aim of our review was to identify all digital and mannequin maxillofacial simulators available for education and training, highlight their benefit, and critically assess the evidence in support of these educational resources. MATERIALS AND METHODS/METHODS:We performed a comprehensive literature review of all peer-reviewed publications of digital and mannequin simulators that met the inclusion criteria, defined as any simulator used in education or training. All simulators used in surgical planning were excluded. Before the query, it was hypothesized that most studies would be descriptive in nature and supported by low levels of evidence. Literature search strategies included the use of multiple combinations of key search terms, review of titles and abstracts, and precise identification of the use of the simulator described. All statistics were descriptive. RESULTS:The primary search yielded 259 results, from which 22 total simulators published on from 2001 to 2016 were identified using the inclusion and exclusion criteria: 10 virtual reality haptic-based simulators, 6 physical model simulators, and 6 Web-based simulators used for a variety of procedures such as dental skills, instrument handling, orthognathic surgery (Le Fort I osteotomy, vertical ramus osteotomy, bilateral sagittal split ramus osteotomy), genioplasty, bone grafting, sinus surgery, cleft lip repair, orbital floor repair, and oral biopsy. Only 9 formalized studies were completed; these were classified as low-level evidence-based cohort studies (Levels IV and V). All other simulator reports were descriptive in nature. There were no studies with high levels of evidence completed (Level I to III). CONCLUSIONS:The results of this review suggest that, although seemingly beneficial to the trainee in maxillofacial surgery, simulation in education in this field is an underused commodity because of the significant lack of scientific and validated study designs reported on in the literature thus far. The maxillofacial and simulation communities would benefit from studies on utility and efficacy with higher levels of evidence.
PMID: 30081008
ISSN: 1531-5053
CID: 3226292
The role of 3D printing in treating craniomaxillofacial congenital anomalies
Lopez, Christopher D; Witek, Lukasz; Torroni, Andrea; Flores, Roberto L; Demissie, David B; Young, Simon; Cronstein, Bruce N; Coelho, Paulo G
Craniomaxillofacial congenital anomalies comprise approximately one third of all congenital birth defects and include deformities such as alveolar clefts, craniosynostosis, and microtia. Current surgical treatments commonly require the use of autogenous graft material which are difficult to shape, limited in supply, associated with donor site morbidity and cannot grow with a maturing skeleton. Our group has demonstrated that 3D printed bio-ceramic scaffolds can generate vascularized bone within large, critical-sized defects (defects too large to heal spontaneously) of the craniomaxillofacial skeleton. Furthermore, these scaffolds are also able to function as a delivery vehicle for a new osteogenic agent with a well-established safety profile. The same 3D printers and imaging software platforms have been leveraged by our team to create sterilizable patient-specific intraoperative models for craniofacial reconstruction. For microtia repair, the current standard of care surgical guide is a two-dimensional drawing taken from the contralateral ear. Our laboratory has used 3D printers and open source software platforms to design personalized microtia surgical models. In this review, we report on the advancements in tissue engineering principles, digital imaging software platforms and 3D printing that have culminated in the application of this technology to repair large bone defects in skeletally immature transitional models and provide in-house manufactured, sterilizable patient-specific models for craniofacial reconstruction.
PMCID:6117201
PMID: 29781248
ISSN: 2472-1727
CID: 3129602
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
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
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
Biocompatibility and degradation properties of WE43 Mg alloys with and without heat treatment: In vivo evaluation and comparison in a cranial bone sheep model
Torroni, Andrea; Xiang, Chongchen; Witek, Lukasz; Rodriguez, Eduardo D; Coelho, Paulo G; Gupta, Nikhil
PURPOSE: Orthopedic and maxillofacial bone fractures are routinely treated by titanium internal fixation, which may be prone to exposure, infection or intolerance. Magnesium (Mg) and its alloys represent promising alternatives to produce biodegradable osteosynthesis devices, with biocompatibility and, specifically, hydrogen gas production during the degradation process, being the main drawback. Aim of this study is to test and compare biocompatibility, degradation rate and physiscochemical properties of two Mg-alloys to identify which one possesses the most suitable characteristics to be used as resorbable hardware in load-bearing fracture sites. MATERIALS AND METHODS: As-cast (WE43) and T5 Mg-alloys were tested for biocompatibility, physical, mechanical and degradation properties. Microstructure was assessed by optical microscopy, scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS); mechanical properties were tested utilizing quasi-static compression and failure analysis. Locoregional biocompatibility was tested by sub-periosteal implantation on the fronto-nasal region of large-animal model (sheep): regional immunoreaction and metal accumulation was analyzed by LA-ICP of tributary lymph-nodes, local reactions were analyzed through histological preparation including bone, implant and surrounding soft tissue. RESULTS: Mechanically, T5 alloy showed improvement in strength compared to the as-cast. Lymph-node Mg accumulation depicted no differences between control (no implant) and study animals. Both alloys showed good biocompatibility and osteogenesis-promoting properties. CONCLUSION: This study demonstrated excellent biocompatibility and osteogenesis-promoting capabilities of the tested alloys, providing a platform for further studies to test them in a maxillofacial fracture setting. T-5 alloy displayed more stability and decreased degradation rate than the as-cast.
PMID: 29089254
ISSN: 1878-4119
CID: 2765892
Osseodensification for enhancement of spinal surgical hardware fixation
Lopez, Christopher D; Alifarag, Adham M; Torroni, Andrea; Tovar, Nick; Diaz-Siso, J Rodrigo; Witek, Lukasz; Rodriguez, Eduardo D; Coelho, Paulo G
Integration between implant and bone is an essential concept for osseous healing requiring hardware placement. A novel approach to hardware implantation, termed osseodensification, is described here as an effective alternative. 12 sheep averaging 65kg had fixation devices installed in their C2, C3, and C4 vertebral bodies; each device measured 4mm diameterx10mm length. The left-sided vertebral body devices were implanted using regular surgical drilling (R) while the right-sided devices were implanted using osseodensification drilling (OD). The C2 and C4 vertebra provided the t=0 in vivo time point, while the C3 vertebra provided the t=3 and t=6 week time points, in vivo. Structural competence of hardware was measured using biomechanical testing of pullout strength, while the quality and degree of new bone formation and remodeling was assessed via histomorphometry. Pullout strength demonstrated osseodensification drilling to provide superior anchoring when compared to the control group collapsed over time with statistical significance (p<0.01). On Wilcoxon rank signed test, C2 and C4 specimens demonstrated significance when comparing device pullout (p=0.031) for both, and C3 pullout tests at 3 and 6 weeks collapsed over time had significance as well (p=0.027). Percent bone-to-implant contact (%BIC) analysis as a function of drilling technique demonstrated an OD group with significantly higher values relative to the R group (p<0.01). Similarly, percent bone-area-fraction-occupancy (BAFO) analysis presented with significantly higher values for the OD group compared to the R group (p=0.024). As a function of time, between 0 and 3 weeks, a decrease in BAFO was observed, a trend that reversed between 3 and 6 weeks, resulting in a BAFO value roughly equivalent to the t=0 percentage, which was attributed to an initial loss of bone fraction due to remodeling, followed by regaining of bone fraction via production of woven bone. Histomorphological data demonstrated autologous bone chips in the OD group with greater frequency relative to the control, which acted as nucleating surfaces promoting new bone formation around the implants, providing superior stability and greater bone density. This alternative approach to a critical component of hardware implantation encourages assessment of current surgical approaches to hardware implantation.
PMCID:5434975
PMID: 28113132
ISSN: 1878-0180
CID: 2418102
Use of N-Butyl-2-Cyanoacrylate (Glubran2((R))) in Fractures of Orbital-Maxillo-Zygomatic Complex
Foresta, Enrico; Torroni, Andrea; Gasparini, Giulio; Saponaro, Gianmarco; Longo, Giuliana; Boniello, Roberto; Cervelli, Daniele; Marianetti, Tito Matteo; Pelo, Sandro; Moro, Alessandro
INTRODUCTION: Fractures of the orbital-maxillo-zygomatic complex are among the most common fractures affecting the facial skeleton. Goal of surgical treatment is the realignment of fracture lines for a complete functional and aesthetic rehabilitation. MATERIALS AND METHODS: From January 2008 to January 2011 in the Department of Maxillofacial Surgery of Complesso Integrato Columbus of the Universita Cattolica del Sacro Cuore in Rome, 25 patients, affected by comminute fractures of the anterior wall of the maxillary sinus associated with fractures of the orbital-maxillary complex were selected. The synthesis of the larger fracture fragments was performed by plates and screws (1.5 mm) while a biocompatible glue (N-Butyl-2-Cyanoacrylate-Glubran2((R))) was applied to treat the comminute fractures of the anterior wall of the maxillary sinus. RESULTS AND CONCLUSION: The aim of our article is to report our experience and a review of the literature on application of-Butyl-2-Cyanoacrylate for treatment of comminute fractures of the anterior wall of the maxillary sinus. According to the results achieved in our study the N-Butyl-2-Cyanoacrylate can be indicated to treat comminuted fractures of the anterior wall of the maxillary sinus which could not easily be treated with internal rigid fixation.
PMCID:4511917
PMID: 26225074
ISSN: 0972-8279
CID: 1769942