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Department/Unit:Plastic Surgery

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Parenchymal and stromal tissue regeneration of tooth organ by pivotal signals reinstated in decellularized matrix

He, Ling; Zhou, Jian; Chen, Mo; Lin, Chyuan-Sheng; Kim, Sahng G; Zhou, Yue; Xiang, Lusai; Xie, Ming; Bai, Hanying; Yao, Hai; Shi, Changcheng; Coelho, Paulo G; Bromage, Timothy G; Hu, Bin; Tovar, Nick; Witek, Lukasz; Wu, Jiaqian; Chen, Kenian; Gu, Wei; Zheng, Jinxuan; Sheu, Tzong-Jen; Zhong, Juan; Wen, Jin; Niu, Yuting; Cheng, Bin; Gong, Qimei; Owens, David M; Stanislauskas, Milda; Pei, Jasmine; Chotkowski, Gregory; Wang, Sainan; Yang, Guodong; Zegarelli, David J; Shi, Xin; Finkel, Myron; Zhang, Wen; Li, Junyuan; Cheng, Jiayi; Tarnow, Dennis P; Zhou, Xuedong; Wang, Zuolin; Jiang, Xinquan; Romanov, Alexander; Rowe, David W; Wang, Songlin; Ye, Ling; Ling, Junqi; Mao, Jeremy
Cells are transplanted to regenerate an organs' parenchyma, but how transplanted parenchymal cells induce stromal regeneration is elusive. Despite the common use of a decellularized matrix, little is known as to the pivotal signals that must be restored for tissue or organ regeneration. We report that Alx3, a developmentally important gene, orchestrated adult parenchymal and stromal regeneration by directly transactivating Wnt3a and vascular endothelial growth factor. In contrast to the modest parenchyma formed by native adult progenitors, Alx3-restored cells in decellularized scaffolds not only produced vascularized stroma that involved vascular endothelial growth factor signalling, but also parenchymal dentin via the Wnt/β-catenin pathway. In an orthotopic large-animal model following parenchyma and stroma ablation, Wnt3a-recruited endogenous cells regenerated neurovascular stroma and differentiated into parenchymal odontoblast-like cells that extended the processes into newly formed dentin with a structure-mechanical equivalency to native dentin. Thus, the Alx3-Wnt3a axis enables postnatal progenitors with a modest innate regenerative capacity to regenerate adult tissues. Depleted signals in the decellularized matrix may be reinstated by a developmentally pivotal gene or corresponding protein.
PMID: 31114073
ISSN: 1476-1122
CID: 3920582

Preoperative Imaging for Facial Transplant: A Guide for Radiologists

Prabhu, Vinay; Plana, Natalie M; Hagiwara, Mari; Diaz-Siso, J Rodrigo; Lui, Yvonne W; Davis, Adam J; Sliker, Clint W; Shapiro, Maksim; Moin, Adnaan S; Rodriguez, Eduardo D
Facial transplant (FT) is a viable option for patients with severe craniomaxillofacial deformities. Transplant imaging requires coordination between radiologists and surgeons and an understanding of the merits and limitations of imaging modalities. Digital subtraction angiography and CT angiography are critical to mapping vascular anatomy, while volume-rendered CT allows evaluation of osseous defects and landmarks used for surgical cutting guides. This article highlights the components of successful FT imaging at two institutions and in two index cases. A deliberate stepwise approach to performance and interpretation of preoperative FT imaging, which consists of the modalities and protocols described here, is essential to seamless integration of the multidisciplinary FT team. ©RSNA, 2019 See discussion on this article by Lincoln .
PMID: 31125293
ISSN: 1527-1323
CID: 3921042

Classification of Subtypes of Apert Syndrome, Based on the Type of Vault Suture Synostosis

Lu, Xiaona; Sawh-Martinez, Rajendra; Jorge Forte, Antonio; Wu, Robin; Cabrejo, Raysa; Wilson, Alexander; Steinbacher, Derek M; Alperovich, Michael; Alonso, Nivaldo; Persing, John A
Background/UNASSIGNED:Apert syndrome patients are different in clinical pathology, including obstructive sleep apnea, cleft palate, and mental deficiency. These functional deficiencies may be due to anatomic deformities, which may be caused by different forms of associated suture fusion. Therefore, a classification system of Apert syndrome based on the type of craniosynostosis pattern might be helpful in determining treatment choices. Methods/UNASSIGNED:CT scans of 31 unoperated Apert syndrome and 51 controls were included and subgrouped as: class I. Bilateral coronal synostosis; class II. Pansynostosis; and class III. Perpendicular combination synostosis: a. unilateral coronal and metopic synostosis; b. sagittal with bilateral/unilateral lambdoid synostosis; and c. others. Results/UNASSIGNED:Class I is the most common (55%) subtype. The cranial base angulation of class I was normal; however, the cranial base angulation on the cranium side of the skull in class II increased 12.16 degrees (P = 0.006), whereas the facial side cranial base angle of class IIIa decreased 4.31 degrees (P = 0.035) over time. The external cranial base linear measurements of class I showed more evident reduction in anterior craniofacial structures than posterior, whereas other subtypes developed more severe shortening in the posterior aspects. Conclusions/UNASSIGNED:Bicoronal synostosis is the most common subtype of Apert syndrome with the normalized cranial base angulation. Combined pansynostosis patients have flatter cranial base, whereas the combined unilateral coronal synostosis have a kyphotic cranial base. Class I has more significant nasopharyngeal airway compromise in a vertical direction, whereas classes II and III have more limited oropharyngeal space.
PMCID:6467634
PMID: 31044122
ISSN: 2169-7574
CID: 3918422

Osteointegrative and microgeometric comparison between micro-blasted and alumina blasting/acid etching on grade II and V titanium alloys (Ti-6Al-4V)

Granato, Rodrigo; Bonfante, Estevam A; Castellano, Arthur; Khan, Rehan; Jimbo, Ryo; Marin, Charles; Morsi, Sara; Witek, Lukasz; Coelho, Paulo G
This study evaluated the effect of alumina-blasted/acid-etched (AB/AE) or microabrasive blasting (C3-Microblasted) surface treatment on the osseointegration of commercially-pure Ti (grade II) and Ti-6Al-4V alloy (grade V) implants compared to as-machined surfaces. Surface characterization was performed by scanning electron microscopy and optical interferometry (IFM) to determine roughness parameters (Sa and Sq, n = 3 per group). One-hundred forty-four implants were placed in the radii of 12 beagle dogs, for histological (n = 72, bone-to-implant contact - BIC and bone-area-fraction occupancy -BAFO) and torque to interface failure test at 3 and 6 weeks (n = 72). SEM and IFM revealed a significant increase in surface texture for AB/AE and C3-Microblasted surfaces compared to machined surface, regardless of titanium substrate. Torque-to-interface failure test showed significant increase in values from as-machined to AB/AE and to C3-Microblasted. Considering time in vivo, alloy grade, and surface treatment, the C3-microblasted presented higher mean BIC values relative to AB/AE and machined surfaces for both alloy types. BAFO levels were significantly higher for both textured surfaces groups relative to the machined group at 3 weeks, but differences were not significant between the three surfaces for each alloy type at 6 weeks. Surface treatment resulted in roughness that improved osseointegration in Grade II and V titanium substrates.
PMID: 31146202
ISSN: 1878-0180
CID: 3921772

Analysis of Immediate versus Delayed Sternal Reconstruction with Pectoralis Major Advancement Versus Turnover Muscle Flaps

Kamel, George N; Jacobson, Joshua; Rizzo, Amanda M; Kinkhabwala, Corin; Lalezar, Frank; Draper, Lawrence; Tepper, Oren M; Garfein, Evan S; Weichman, Katie E
BACKGROUND: The pectoralis major muscle flap is a versatile reconstructive option for deep sternal wound infections (DSWI). The timing and surgical technique of bilateral pectoralis major muscle advancement flaps versus unilateral pectoralis major muscle turnover and unilateral pectoralis major muscle advancement flap on patient outcomes remain to be elucidated. The purpose of this investigation was to compare timing, immediate versus delayed reconstruction, and the surgical technique in patients with deep sternal wounds infections on patient outcomes. METHODS: A retrospective review of patients who underwent sternal reconstruction with pectoralis major muscle was conducted. Patients diagnosed with DSWI after undergoing cardiac surgery were included for analysis. Patients were divided by flap timing and flap type for analyses. Bivariate tests were performed to compare patient clinical characteristics. Outcomes of interest were rates of postoperative complications, same admission mortality, reoperation, readmission, operating room time, and length of stay. RESULTS: = 0.019). CONCLUSION/CONCLUSIONS: Patients who underwent pectoralis major muscle advancement flaps had lower incidence of tissue necrosis. Furthermore, the timing of immediate sternal reconstruction was associated with a decreased hospital length of stay.
PMID: 31075802
ISSN: 1098-8947
CID: 3919302

Quadruple Perforator Flaps for Primary Closure of Large Myelomeningoceles: An Evaluation of the Butterfly Flap Technique

Rankin, Timothy M; Wormer, Blair A; Tokin, Christopher; Kaoutzanis, Christodoulos; Al Kassis, Salam; Wellons, John C; Braun, Stephane
INTRODUCTION/BACKGROUND:Myelomeningocele is the most common open neural tube defect. A quadruple rotation-VY advancement flap (butterfly flap) was recently reported for closure of large myelomeningocele defects; however, no series has been reproduced to evaluate this technique. The objective of this study was to describe our experience with this technique. MATERIALS AND METHODS/METHODS:We reviewed all infants born with large myelomeningocele defects who underwent butterfly flap closure over a 2-year period. Demographics, defect size, operative details, and complications were used to generate descriptive statistics. RESULTS:From June 2015 to January 2018, 7 infants met inclusion criteria. Mean defect width was 52% ± 0.11 of the back, representing 21% ± 0.09 of the total back area. Only 1 child had central breakdown. All patients had some peripheral skin dehiscence that occurred on postoperative day 12 ± 7, and these were treated with outpatient wound care. Four patients returned to the operating room for dehiscence electively. There were no incidences of total flap loss. There were no cases of meningitis or myelomeningocele dehiscence. All patients had successful closure of their myelomeningocele without the use of skin grafts. CONCLUSIONS:The butterfly flap is able to close large myelomeningocele defects and has the potential to improve contour. There are minor wound-healing complications, but in the rare event of central dehiscence, quadruple rotation-VY advancement flaps can be re-advanced. In all cases, a large myelomeningocele was successfully reconstructed with robust full-thickness flaps, and there was no need for skin grafting of donor sites.
PMID: 31085942
ISSN: 1536-3708
CID: 3919582

Association of Regional Cranial Base Deformity and Ultimate Structure in Crouzon Syndrome

Lu, Xiaona; Jorge Forte, Antonio; Sawh-Martinez, Rajendra; Wu, Robin; Cabrejo, Raysa; Steinbacher, Derek M; Alperovich, Michael; Alonso, Nivaldo; Persing, John A
BACKGROUND:Considerable craniofacial features of Crouzon syndrome are attributed to the dysmorphology of the cranial base. As cephalometric studies have focused mainly on the facial deformity, rather than the cranial base, the underlying cause of deformity is not as well understood. Therefore, the authors compared the cranial base development of Crouzon syndrome to controls to trace the timing of deformity in the cranial base and face, to analyze their temporal correlation. METHODS:Ninety computed tomographic scans were included (Crouzon, n = 36; controls, n = 54) and divided into five age subgroups. Craniofacial cephalometric measurements were analyzed by Materialise software. RESULTS:The overall cranial base length in Crouzon syndrome compared with controls decreased 8 percent (p = 0.014) on average. The posterior cranial fossa shortening accounted for most of this reduction. The cranial base displaced with the distances from basion, sella, and ethmosphenoid to posterior nasal spine shortened by 21%, 18%, and 16%, respectively (all p < 0.01) during life. Although the cranial base angle on intracranial surface remains normal, the angles on facial surface narrowed were reduced. CONCLUSIONS:The cranial base deformity of Crouzon syndrome consists of the whole skull base and particularly anterior skull base shortening early, leading to a compensatory widened anterior skull base. However, when this widening did not compensate fully for the rapid enlargement of the brain, the posterior skull base displaced inferiorly and became kyphotic. The cranial base deformity develops sequentially anterior to posterior in a probable cascade of influence pattern. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Risk, II.
PMID: 31136487
ISSN: 1529-4242
CID: 3921412

Unique Venous Anatomy in a Face Donor

Kantar, Rami S; Ceradini, Daniel J; Rodriguez, Eduardo D
PMID: 31145439
ISSN: 2168-6092
CID: 3921732

Vein Size Mismatch Increases Flap Failure in Lower Extremity Trauma Free Flap Reconstruction

Lee, Z-Hye; Alfonso, Allyson R; Stranix, John T; Anzai, Lavinia; Daar, David A; Ceradini, Daniel J; Levine, Jamie P; Saadeh, Pierre B; Thanik, Vishal
BACKGROUND: Venous outflow problems are the most common reasons for perioperative flap complications. Size mismatch in venous anastomoses poses a theoretical problem by promoting turbulent flow and subsequent thrombus formation. The purpose of this study was to determine if increased vein size mismatch is predictive of flap failure. METHODS: Retrospective review of our institutional flap registry from 1979 to 2016 identified 410 free flaps performed for reconstruction of lower extremity trauma. Patient demographics, flap characteristics, and flap outcomes were examined. Venous size mismatch was defined as a difference in size ≥ 1 mm between the recipient vein and flap vein. RESULTS: = 0.045; odds ratio: 2.58). CONCLUSION/CONCLUSIONS: Flaps with vein size mismatch ≥ 1 mm demonstrated increased flap complication rates in the setting of end-to-end venous anastomoses. End-to-side anastomosis was preferentially used in vein size mismatch and carried a higher risk of flap failure. Our results support using veins of similar size for anastomosis whenever feasible to protect against flap complications.
PMID: 31067583
ISSN: 1098-8947
CID: 3919042

Applications of Bone Morphogenetic Protein-2: Alternative Therapies in Craniofacial Reconstruction

Fisher, Mark; Yee, Kristen; Alba, Brandon; Tanna, Neil; Bastidas, Nicholas; Bradley, James P
Large defects of the craniofacial skeleton can be exceedingly difficult to reconstruct since autologous bone grafts are limited by donor site morbidity and alloplastic implants have low biocompatibility. Bone morphogenetic proteins (BMPs) in craniofacial reconstruction have been used with mixed outcomes and complication concerns; however, results for specific indications have been promising.In alveolar clefts, cranial vault defects, mandibular defects, and rare Tessier craniofacial clefts, BMP-2 impregnated in collagen matrix was looked at as an alternative therapy for challenging cases. In cases where structural support was required, BMP-2 was used as part of a construct with bio-resorbable plates. Demineralized bone was added in certain cases.The authors described specific indications, detailed surgical techniques, and a review of the current literature regarding the use of BMP-2 in craniofacial reconstruction. BMP-2 is a viable option for craniofacial reconstruction to decrease donor-site morbidity or when alternatives are contraindicated. It is not recommended for routine use or in the oncologic setting but should currently be reserved as an alternative therapy for complex cases with limited options.Bone morphogenetic proteins are a promising, emerging option for complex craniofacial reconstruction. Future directions of BMP-2 therapies will become apparent as data from prospective randomized trials emerges.
PMID: 31107382
ISSN: 1536-3732
CID: 3920262