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Department/Unit:Plastic Surgery

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Characterization of Adipose-Derived Mesenchymal Stem Cell Combinations for Vascularized Bone Engineering

Valenzuela, Cristian D; Allori, Alexander C; Reformat, Derek D; Sailon, Alexander M; Allen, Robert J Jr; Davidson, Edward H; Alikhani, Mani; Bromage, Timothy G; Ricci, John L; Warren, Stephen M
Since bone repair and regeneration depend on vasculogenesis and osteogenesis, both of these processes are essential for successful vascularized bone engineering. Using adipose-derived stem cells (ASCs), we investigated temporal gene expression profiles, as well as bone nodule and endothelial tubule formation capacities, during osteogenic and vasculogenic ASC lineage commitment. Osteoprogenitor-enriched cell populations were found to express RUNX2, MSX2, SP7 (osterix), BGLAP (osteocalcin), SPARC (osteonectin), and SPP1 (osteopontin) in a temporally specific sequence. Irreversible commitment of ASCs to the osteogenic lineage occurred between days 6 and 9 of differentiation. Endothelioprogenitor-enriched cell populations expressed CD34, PECAM1 (CD31), ENG (CD105), FLT1 (Vascular endothelial growth factor [VEGFR1]), and KDR (VEGFR2). Capacity for microtubule formation was evident in as early as 3 days. Functional capacity was assessed in eight coculture combinations for both bone nodule and endothelial tubule formation, and the greatest expression of these end-differentiation phenotypes was observed in the combination of well-differentiated endothelial cells with less-differentiated osteoblastic cells. Taken together, our results demonstrate vascularized bone engineering utilizing ASCs is a promising enterprise, and that coculture strategies should focus on developing a more mature vascular network in combination with a less mature osteoblastic stromal cell.
PMID: 23343199
ISSN: 1937-3341
CID: 250382

FK506 and nerve regeneration: past, present, and future

Konofaos, Petros; Terzis, Julia K
Promoting neurological recovery requires strategies that simultaneously provide protection to injured neurons and increase the numbers of neurons that extend axons while inducing more rapid and extensive axon regeneration across long nerve gaps. An agent that facilitates the speed and success of reinnervation will have direct applicability to the clinical management of severe peripheral nerve injuries. The immunosuppressive drug FK506 has been proven to have neuroprotective and neurotrophic actions in experimental models, increasing neurite elongation and accelerating the rate of nerve regeneration in vitro and in vivo. This review examines the role played by FK506, with primary focus on its role as a neurotrophic agent and its potential clinical use as a promoter of neurological recovery following peripheral nerve injuries.
PMID: 23322540
ISSN: 1098-8947
CID: 249022

Ten-year Evolution Utilizing Computer-Assisted Reconstruction for Giant Ameloblastoma

Broer, P Niclas; Tanna, Neil; Franco, Peter B; Thanik, Vishal D; Levine, Steven M; Garfein, Evan S; Saadeh, Pierre B; Ceradini, Daniel J; Hirsch, David L; Levine, Jamie P
Background The authors describe our current practice of computer-aided virtual planned and pre-executed surgeries using microvascular free tissue transfer with immediate placement of implants and dental prosthetics.Methods All patients with ameloblastomas treated at New York University (NYU) Medical Center during a 10-year period from September 2001 to December 2011 were identified. Of the 38 (36 mandible/2 maxilla) patients that were treated in this time period, 20 were identified with advanced disease (giant ameloblastoma) requiring aggressive resection. Reconstruction of the resultant defects utilized microvascular free tissue transfer with an osseocutaneous fibular flap in all 20 of these patients.Results Of the patients reconstructed with free vascularized tissue transfer, 35% (7/20) developed complications. There were two complete flap failures with consequent contralateral fibula flap placement. Sixteen patients to date have undergone placement of endosteal implants for complete dental rehabilitation, nine of which received immediate placement of the implants at the time of the free flap reconstruction. The three most recent patients received immediate placement of dental implants at the time of microvascular free tissue transfer as well as concurrent placement of dental prosthesis.Conclusions To our knowledge, this patient cohort represents the largest series of comprehensive computer aided free-flap reconstruction with dental restoration for giant type ameloblastoma.
PMID: 23277406
ISSN: 1098-8947
CID: 248372

Surface characterisation and bonding of Y-TZP following non-thermal plasma treatment

Valverde, Guilherme B; Coelho, Paulo G; Janal, Malvin N; Lorenzoni, Fabio Cesar; Carvalho, Ricardo M; Thompson, Van P; Weltemann, Klaus-Dieter; Silva, Nelson R F A
OBJECTIVES: (1) To chemically characterise Y-TZP surface via X-ray photoelectron spectroscopy (XPS) and evaluate the surface energy levels (SE) after non-thermal plasma (NTP). (2) To test the microtensile bond strength (MTBS) of Y-TZP bonded to cured composite disks, after a combination of different surface conditioning methods. METHODS: Twenty-four Y-TZP discs (13.5mmx4mm) were obtained from the manufacturer and composite resin (Z-100) discs with similar dimensions were prepared. All discs were polished to 600 grit and divided into 8 groups (n=3 disks each), four control (non-NTP treated) and four experimental (NTP treated for 10s) groups. All groups received one of the four following treatments prior to cementation with RelyxUnicem cement: sand-blasting (SB), a Clearfil ceramic primer (MDP), sand-blasting+MDP (SBMDP), or baseline (B), no treatment. SE readings and surface roughness parameters were statistically analysed (ANOVA, Tukey's, p<0.05). Mixed model and paired samples t-tests were used to compare groups on MTBS. RESULTS: XPS showed increase in O and decrease in C elements after NTP. The polar component increased for BP (42.20mN/m) and SBP (43.77mN/m). MTBS values for groups BP (21.3MPa), SBP (31MPa), MDPP (30.1MPa) and SBMDPP (32.3MPa) were significantly higher in specimens treated with NTP than their untreated counterparts B (9.1MPa), SB (14.4MPa), MDP (17.8MPa) and SBMDP (24.1MPa). CONCLUSIONS: (1) Increase of O and decrease of C led to higher surface energy levels dictated by the polar component after NTP; (2) NTP application increased MTBS values of Y-TZP surfaces.
PMID: 23044388
ISSN: 0300-5712
CID: 240622

Current thoughts for the prevention and treatment of pressure ulcers: using the evidence to determine fact or fiction

Levine, Steven M; Sinno, Sammy; Levine, Jamie P; Saadeh, Pierre B
OBJECTIVE: : To use an evidenced-based approach to better understand the management and treatment of pressure ulcers. BACKGROUND: : Pressure sores are a cause of significant morbidity in the medical community. Although there are a multitude of preventative and treatment options, there remains some degree of uncertainty in the literature in defining the best way to treat and manage pressure sores. METHODS: : An exhaustive literature search was performed using several electronic databases. The search revealed several identified modalities for treatment and/or prevention of pressure ulcers. We then assessed each modality individually for the level of evidence that exists in the most current literature, with preference given to more recent studies (2005 to present). RESULTS: : We reviewed the most relevant, high-level evidence that exists for the following modalities for understanding, preventing, and treating pressure ulcers: wound cleansers, repositioning, negative pressure therapy, debridement, enteral and parenteral feeding, vitamin and mineral supplementation, specialized mattresses, ultrasound therapy, honey, cellular therapy, musculocutaneous and fasciocutaneous flap closure, and other miscellaneous therapies. CONCLUSIONS: : Although many of these modalities are used, we encourage clinicians and health care providers to consider the evidence-based data when deciding how to most appropriately manage their patients' pressure sores.
PMID: 23426346
ISSN: 0003-4932
CID: 232992

Microsurgical breast reconstruction for nipple-sparing mastectomy

Tanna, Neil; Broer, P Niclas; Weichman, Katie E; Alperovich, Michael; Ahn, Christina Y; Allen, Robert J Sr; Choi, Mihye; Karp, Nolan S; Saadeh, Pierre B; Levine, Jamie P
BACKGROUND: : Nipple-sparing mastectomy warrants thorough preoperative evaluation to effectively achieve risk reduction, high patient satisfaction, and improved aesthetic outcome. To the authors' knowledge, this review represents the largest series of microsurgical breast reconstructions following nipple-sparing mastectomies. METHODS: : All patients undergoing nipple-sparing mastectomy with microsurgical immediate breast reconstruction treated at New York University Medical Center (2007-2011) were identified. Patient demographics, breast cancer history, intraoperative details, complications, and revision operations were examined. Descriptive statistical analysis, including t test or regression analysis, was performed. RESULTS: : In 51 patients, 85 free flap breast reconstructions (n = 85) were performed. The majority of flaps were performed for prophylactic indications [n = 55 (64.7 percent)], mostly through vertical incisions [n = 40 (47.0 percent)]. Donor sites included abdominally based [n = 66 (77.6 percent)], profunda artery perforator [n = 12 (14.1 percent)], transverse upper gracilis [n = 6 (7.0 percent)], and superior gluteal artery perforator [n = 1 (1.2 percent)] flaps. The most common complications were mastectomy skin flap necrosis [n = 11 (12.7 percent)] and nipple necrosis [n = 11 (12.7 percent)]. There was no correlation between mastectomy skin flap or nipple necrosis and choice of incision, mastectomy specimen weight, body mass index, or age (p > 0.05). However, smoking history was associated with nipple necrosis (p < 0.01). CONCLUSIONS: : This series represents a high-volume experience with nipple-sparing mastectomy followed by immediate microsurgical reconstruction. When appropriately executed, it can deliver low complication rates. CLINICAL QUESTION/LEVEL OF EVIDENCE: : Therapeutic, IV.
PMID: 23358009
ISSN: 1529-4242
CID: 220302

Discussion: Limited evidence for the effect of presurgical nasoalveolar molding in unilateral cleft on nasal symmetry: a call for unified research [Comment]

Grayson, Barry H
PMID: 23271557
ISSN: 1529-4242
CID: 217962

Best face forward: Virtual modeling and custom device fabrication to optimize craniofacial vascularized composite allotransplantation

Jacobs, Jordan M S; Dec, Wojciech; Levine, Jamie P; McCarthy, Joseph G; Weimer, Katie; Moore, Kurt; Ceradini, Daniel J
Craniofacial vascularized composite allotransplantation is especially challenging when bony components are required. Matching the complex three-dimensional anatomy of the donor and recipient craniofacial skeletons to optimize bony contact and dental occlusion is a time-consuming step in the operating room. Currently, few tools exist to facilitate this process. The authors describe the development of a virtual planning protocol and patient-specific device design to efficiently match the donor and recipient skeletal elements in craniofacial vascularized composite allotransplantation. The protocol was validated in a cadaveric transplant. This innovative planning method allows a "snap-fit" reconstruction using custom surgical guides while maintaining facial height and width and functional occlusion. Postoperative overlay technology in the virtual environment provides an objective outcome analysis.
PMID: 23271519
ISSN: 1529-4242
CID: 217952

Grading lipoaspirate: is there an optimal density for fat grafting?

Allen, Robert J Jr; Canizares, Orlando Jr; Scharf, Carrie; Nguyen, Phuong D; Thanik, Vishal; Saadeh, Pierre B; Coleman, Sydney R; Hazen, Alexes
BACKGROUND: Clinical results of fat grafting have been unpredictable. In this article, the authors hypothesize that centrifugation creates "graded densities" of fat with varying characteristics that influence lipoaspirate persistence and quality. METHODS: Aliquots of human female lipoaspirate (10 cc) were centrifuged for 3 minutes at 1200 g. The bloody and oil fractions were discarded. Subsequently, 1.0 cc of the highest density and lowest density fat was separated for lipoinfiltration or analysis. Highest density or lowest density fat grafted into adult FVB mice was harvested at 2 and 10 weeks to quantify short- and long-term persistence, respectively. Progenitor cell number and expression of vascular endothelial growth factor, stromal cell-derived factor-1alpha, platelet-derived growth factor, and adiponectin were analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively. RESULTS: Greater percentages of highest density fat grafts remain at 2 and 10 weeks after injection compared with lowest density fat grafts (85.4 +/- 1.9 percent versus 62.3 +/- 0.1 percent, p = 0.05; and 60.8 +/- 4.9 versus 42.2 +/- 3.9, p < 0.05, respectively). Highest density fractions contain more progenitor cells per gram than lowest density fractions (2.0 +/- 0.2-fold increase, p < 0.01). Furthermore, concentrations of vascular endothelial growth factor, stromal vascular fraction, platelet-derived growth factor, and adiponectin are all elevated in highest density compared with lowest density fractions (34.4 percent, p < 0.01; 34.6 percent, p < 0.05; 52.2 percent, p < 0.01; and 45.7 percent, p < 0.05, respectively). CONCLUSIONS: Greater percentages of highest density fractions of lipoaspirate persist over time compared with lowest density fractions. A vasculogenic mechanism appears to contribute significantly, as highest density fractions contain more progenitor cells and increased concentrations of several vasculogenic mediators than lowest density fractions.
PMID: 23271517
ISSN: 1529-4242
CID: 217942

Treatment and outcomes of fingertip injuries at a large metropolitan public hospital

Weichman, Katie E; Wilson, Stelios C; Samra, Fares; Reavey, Patrick; Sharma, Sheel; Haddock, Nicholas T
BACKGROUND: Fingertip injuries are the most common hand injuries presenting for acute care. Treatment algorithms have been described based on defect size, bone exposure, and injury geometry. The authors hypothesized that despite accepted algorithms, many fingertip injuries can be treated conservatively. METHODS: A prospectively collected retrospective review of all fingertip injuries presenting to Bellevue Hospital between January and May of 2011 was conducted. Patients were entered into an electronic database on presentation. Follow-up care was tracked through the electronic medical record. Patients lost to follow-up were questioned by means of telephone. Patients were analyzed based on age, mechanism of injury, handedness, occupation, wound geometry, defect size, bone exposure, emergency room procedures performed, need for surgical intervention, and outcome. RESULTS: One hundred fingertips were injured. Injuries occurred by crush (46 percent), laceration (30 percent), and avulsion (24 percent). Sixty-four percent of patients healed without surgery, 18 percent required operative intervention, and 18 percent were lost to follow-up. Patients requiring operative intervention were more likely to have a larger defect (3.28 cm versus 1.75 cm, p < 0.005), volar oblique injury (50 percent versus 8.8 percent, p < 0.005), exposed bone (81.3 percent versus 35.3 percent, p < 0.005), and an associated distal phalanx fracture (81.3 percent versus 47.1 percent, p < 0.05). Patients requiring surgical intervention had a longer average return to work time when compared with those not requiring surgical intervention (4.33 weeks versus 2.98 weeks, p < 0.001). CONCLUSION: Despite current accepted algorithms, many fingertip injuries can be treated nonoperatively to achieve optimal sensation, fine motor control, and earlier return to work. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
PMID: 22965236
ISSN: 1529-4242
CID: 217762