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ABSTRACT: BACKGROUND: The purpose of this prospective randomized study was to compare landmark- to ultrasound-guided central venous access when performed by pediatric surgeons. The American College of Surgeons advocates for use of ultrasound in central venous catheter placement; however, this is not universally embraced by pediatric surgeons. Complication risk correlates positively with number of venous cannulation attempts. STUDY DESIGN: With IRB approval, a randomized prospective study of children under 18 years of age undergoing tunneled central venous catheter placement was performed. Patient accrual was based on power analysis. Exclusion criteria included known nonpatency of a central vein or coagulopathy. After randomization, the patients were assigned to either ultrasound-guided internal jugular vein access or landmark-guided subclavian/internal jugular vein access. The primary outcomes measure was number of attempts at venous cannulation. Secondary outcomes measures included: access times, number of arterial punctures, and other complications. Continuous variables were compared using 2-tailed Student's t-test. Discrete variables were analyzed with chi-square. Significance was defined as p < 0.05. RESULTS: There were 150 patients enrolled between April 2008 and September 2011. There was no difference when comparing demographic data. Success at first attempt was achieved in 65% of patients in the ultrasound group vs 45% in the landmark group (p = 0.021). Success within 3 attempts was achieved in 95% of ultrasound group vs 74% of landmark group (p = 0.0001). CONCLUSIONS: Ultrasound reduced the number of cannulation attempts necessary for venous access. This indicates a potential to reduce complications when ultrasound is used by pediatric surgeons.
Journal of the American College of Surgeons 03/2013; · 4.55 Impact Factor
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Digestive Diseases and Sciences 06/2011; 56(9):2528-31. · 2.12 Impact Factor
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ABSTRACT: An understanding of the molecular mechanisms controlling bone formation is central to skeletal tissue engineering efforts. The observation that immature animals are able to heal calvarial defects while adult animals are not has proven to be a useful tool for examining these mechanisms. Thus, the authors compared expression of sclerostin, a bone inhibitor, between the calvariae of juvenile and adult mice.
Parietal bone was harvested from juvenile (6-day-old; n = 20) and adult (60-day-old; n = 20) mice. Sclerostin transcript and protein levels were compared between the parietal bone of juvenile and adult mice using polymerase chain reaction, Western blotting, and immunohistochemistry. Finally, osteoblasts from the parietal bone of juvenile and adult mice were harvested and cultured under osteogenic differentiation conditions with and without recombinant sclerostin (200 ng/ml). Terminal osteogenic differentiation was assessed at 21 days with alizarin red staining.
Polymerase chain reaction, Western blot analysis, and immunohistochemistry all confirmed greater expression of sclerostin in the parietal bone of adult mice when compared with that of juvenile mice. Osteoblasts, whether from juvenile or adult parietal bones, demonstrated reduced capacity for osteogenic differentiation when exposed to recombinant sclerostin.
Given the role of sclerostin in inhibiting bone formation, the authors' findings suggest that differences in expression levels of sclerostin may play a role in the differential regenerative capacity of calvariae from juvenile and adult animals. These findings suggest it as a potential target to abrogate in future tissue engineering studies.
Plastic and reconstructive surgery 02/2011; 127(2):595-602. · 2.74 Impact Factor
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ABSTRACT: Background. We investigated the effect of laparoscopic sleeve gastrectomy (LSG) on morbidly obese diabetics and examined the short-term impact of LSG on diabetic medication cost. Methods. A prospective database of consecutive bariatric patients was reviewed. Morbidly obese patients with type 2 diabetes who underwent LSG were included in the study. Age, gender, body mass index (BMI), diabetic medication use, glucose, insulin, and HbA1c levels were documented preoperatively, and at 2 weeks, 2 months, 6 months, and 12 months postoperatively. Insulin resistance was estimated using the homeostatic model assessment (HOMA). Use and cost of diabetic medications were followed. Results. Of 178 patients, 22 were diabetics who underwent LSG. Diabetes remission was observed in 62% of patients within 2 months and in 75% of patients within 12 months. HOMA-IR improved after only two weeks following surgery (16.5 versus 6.6, P < 0.001). Average number of diabetic medications decreased from 2.2 to <1, within 2 weeks after surgery; corresponding to a diabetes medication cost savings of 80%, 91%, 99%, and 99.7% after 2 weeks, 2 months, 6 months, and 12 months, respectively. Conclusion. Morbidly obese patients with diabetes who undergo LSG have high rates of diabetes remission early after surgery. This translates to a significant medication cost savings.
Journal of obesity 01/2011; 2011:350523.
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ABSTRACT: Moderate to severe hereditary spherocytosis (HS) is treated with splenectomy. However, total splenectomy leads to decreased immunologic function with the risk of overwhelming postsplenectomy sepsis. Splenic preservation is postulated as a method to avoid this potentially fatal complication. Although mainly performed through laparotomy, we report our experience with a laparoscopic approach to partial splenectomy for HS.
A retrospective review was conducted on 9 laparoscopic partial splenectomies performed for HS at our institution. Follow-up was from 1 to 3.5 years. Data included preoperative and postoperative hemoglobin, absolute reticulocyte count, splenic size, operative time, complications, and length of stay.
All patients successfully underwent laparoscopic partial splenectomy with a radiologically determined upper-pole remnant of 10% to 30% and preservation of the blood supply through the upper short gastric arteries. The mean preoperative spleen length was 13 cm. Mean hospital stay was 3.6 days (range, 1-6 days). There was 1 intraoperative complication (a small bowel tear during spleen extraction) and 2 minor postoperative complications (ileus and wound infection). One patient underwent completion total splenectomy 2 years after partial splenectomy.
Laparoscopic partial splenectomy is a feasible and effective procedure that addresses the hematologic consequences of HS while retaining a portion of functional spleen, in addition to conferring the advantages of laparoscopy.
Journal of Pediatric Surgery 08/2010; 45(8):1682-6. · 1.45 Impact Factor
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ABSTRACT: Craniosynostosis, the premature fusion of cranial sutures, is a common congenital defect. In vivo models for studying cranial suture biology impose inherent restrictions on tissue accessibility and manipulation. The present study was performed to investigate the utility of the renal capsule assay in overcoming these limitations and providing a reproducible model system for studying cranial suture morphogenesis and fate.
The posterior frontal suture, which fuses physiologically, and the coronal and sagittal sutures, which remain patent, were dissected from postnatal and embryonic mouse calvaria and placed under the renal capsule of syngeneic recipient mice (n = 72 in total). Sutures were harvested from 1-14 days after transplantation for histological and morphometric analysis. Suture transplants were compared with nonmanipulated sutures at equivalent developmental stages. The derivation of cells associated with the growing transplants was analyzed using beta-actin-GFP (green fluorescent protein) transgenic mice.
Sutures transplanted under the renal capsule maintained normal suture morphology and fate with the posterior frontal suture fusing and the coronal and sagittal sutures remaining patent. In posterior frontal suture transplants, the fusion process mimicked in vivo suture fusion with a delay of 1-2 days. In comparison to in vivo suture complexes, transplant thickness and trabeculation were significantly increased. In addition, we found that osteoblasts within the growing transplant were derived from the transplant itself rather than the host.
The renal capsule supports the growth of cranial sutures. In this system transplanted sutures recapitulate the anatomical development and fate (fusion or patency) of cranial sutures in vivo. This model system will facilitate controlled ex vivo manipulations of both embryonic and postnatal sutures.
Cells Tissues Organs 08/2009; 190(6):336-46. · 2.20 Impact Factor
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ABSTRACT: Congenital diaphragm anomalies, including eventration, Morgagni diaphragmatic hernias (M-CDH), and Bochdalek diaphragmatic hernias (B-CDH), have been successfully repaired by using minimally invasive surgery (MIS). However, some reports have shown a high recurrence rate for some defects, potentially due to difficulty associated with the rigid instruments. Robotic surgery may help close diaphragmatic anomalies more effectively. In this paper, we present a series of 8 consecutive patients with diaphragmatic anomalies who underwent robotic repair.
We retrospectively reviewed patients with diaphragmatic anomalies. There were 2 patients with eventration, 5 with B-CDH, and 1 with M-CDH. All procedures were performed by using the Standard Da Vinci surgical robot (Intuitive Surgical, Sunnyvale, CA) with one camera arm (5-mm two-dimensional scope) and two instrument arms (5 mm).
Average age was 3.9 months (4 days to 12 months). Average weight was 3.6 kg (range, 2.2-10.5). Four B-CDH patients were approached through the chest and 1 from the abdomen. The patient with M-CDH had an abdominal repair, and both eventrations were performed from the chest. One B-CDH and 1 eventration were converted to thoracoscopic procedures. Average operative time was 1 hour and 20 minutes. One recurrence developed in a relatively large B-CDH repair that was closed primarily. Average follow-up was 20 months.
Robotic surgery is safe and effective for repairing diaphragm anomalies in small children. Although we prefer the thoracic approach for repairing the B-CDH, occasionally smaller newborns-perhaps those less than 2.5 kg-may do better with the abdominal approach, since the articulating instruments requiring a significant length in order to maneuver.
Journal of Laparoendoscopic & Advanced Surgical Techniques 04/2009; 19 Suppl 1:S123-7. · 1.40 Impact Factor
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ABSTRACT: Craniosynostosis, the premature fusion of one or more cranial sutures, is a common developmental disorder resulting in morphologic and functional consequences. The rat model is useful for studying pathologic and normal suture fusion because the posterior frontal suture undergoes fusion but the remaining sutures remain patent. The authors investigated the influence of regional posterior frontal dura mater on the overlying suture morphology and fate.
In 8-day-old Sprague-Dawley rats, an 8-mm calvarial disk was excised without disrupting the underlying dura mater (n = 22) and flipped so that the previously ectocranial aspect was adjacent to the dura mater. The animals were humanely killed after 5, 7, 9, 11, and 28 days, and the posterior frontal sutures were analyzed histologically. A comparison was made to control animals in which the disk was excised and then placed back into its anatomical position (n = 5). Immunohistochemistry of the transforming growth factor (TGF)-beta isoforms was performed to investigate their differential, temporal, and spatial expression.
Posterior frontal suture fusion occurred on the side adjacent to the dura mater (previously patent ectocranial aspect) in an anterior-to-posterior direction, similar to that in the control group. There was specific expression of the TGF-beta isoforms in the dura mater and suture mesenchyme adjacent to the dura mater.
Regional dura mater plays an important role in suture morphology, and the posterior frontal-associated dura mater possesses potent, pro-osteogenic signals that influence the overlying suture fate. The differential expression pattern of TGF-beta signaling from the dura mater further supports the regional paracrine effect of the dura mater.
Plastic and reconstructive surgery 03/2009; 123(2):463-9. · 2.74 Impact Factor
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ABSTRACT: The tremendous diversity in vertebrate skull formation illustrates the range of forms and functions generated by varying genetic programs. Understanding the molecular basis for this variety may provide us with insights into mechanisms underlying human craniofacial anomalies. In this study, we provide evidence that the anuran Xenopus laevis can be developed as a simplified model system for the study of cranial ossification and suture patterning. The head structures of Xenopus undergo dramatic remodelling during metamorphosis; as a result, tadpole morphology differs greatly from the adult bony skull. Because of the extended larval period in Xenopus, the molecular basis of these alterations has not been well studied.
We examined late larval, metamorphosing, and post-metamorphosis froglet stages in intact and sectioned animals. Using micro-computed tomography (microCT) and tissue staining of the frontoparietal bone and surrounding cartilage, we observed that bone formation initiates from lateral ossification centers, proceeding from posterior-to-anterior. Histological analyses revealed midline abutting and posterior overlapping sutures. To determine the mechanisms underlying the large-scale cranial changes, we examined proliferation, apoptosis, and proteinase activity during remodelling of the skull roof. We found that tissue turnover during metamorphosis could be accounted for by abundant matrix metalloproteinase (MMP) activity, at least in part by MMP-1 and -13.
A better understanding of the dramatic transformation from cartilaginous head structures to bony skull during Xenopus metamorphosis may provide insights into tissue remodelling and regeneration in other systems. Our studies provide some new molecular insights into this process.
PLoS ONE 02/2009; 4(1):e3914. · 4.09 Impact Factor
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ABSTRACT: Mortality from ruptured abdominal aortic aneurysms (rAAAs) remains high despite improvements in anesthesia, postoperative intensive care, and surgical techniques. Recent small series and single-center experiences suggest that endovascular aneurysm repair (EVAR) for rAAAs is feasible and may improve short-term survival. However, the applicability of EVAR to all cases of rAAA is unknown. The purpose of this study was to investigate the anatomical suitability of ruptured aneurysms for EVAR as determined by preoperative cross-sectional imaging. A contemporary consecutive series of rAAAs presenting to a tertiary academic center was retrospectively reviewed. Preoperative radiographic imaging was reviewed and assessed for endovascular compatibility based on currently available EVAR devices. Patients with aneurysm morphology demonstrating neck diameter >32 mm, neck length <10 mm, neck angulation >60 degrees, severe iliac tortuosity, or external iliac diameter <6 mm were deemed noncandidates for EVAR. Forty-seven rAAAs were treated over a 10-year period, with 47% of patients presenting with free rupture and 60% of patients transferred from outside hospitals. Five (11%) patients were treated with EVAR, all over the past 2 years, while the remaining 42 patients underwent open repair. Preoperative imaging was available for review in 43 (91%) patients, and morphological measurements indicated that 49% would have been candidates for EVAR with currently available devices. Criteria precluding EVAR in this cohort were inadequate neck length in 73%, unsuitable iliac access in 23%, large neck diameter in 18%, and severe neck angulation in 14%. Overall 30-day mortality was 34%, and 1-year mortality was 42%. Candidates for EVAR were more likely than non-EVAR candidates to be male (95% vs. 68%, p = 0.046) and to have smaller sac diameters (7.0 vs. 8.5 cm, p = 0.02) and longer neck lengths (24.1 vs. 8.6 mm, p < 0.0001); less likely to have a >60 degree angulated neck (10% vs. 45%, p = 0.0002), larger external iliac diameter (8.9 vs. 7.3 mm, p = 0.015), and less blood loss during surgical repair (2.4 vs. 6.0 L, p = 0.02); and more likely to be discharged home (71% vs. 25%, p = 0.05). There were no differences in 30-day, 1-year, or overall mortality between candidates for EVAR and noncandidates. Only 49% of patients with rAAAs in this consecutive series were found to be candidates for EVAR with conventional stent-graft devices. Differences in demographics, aneurysm morphology, and outcomes between candidates and noncandidates undergoing open repair suggest that differential risks apply to ruptured aneurysm patients. Protocols and future reports of EVAR for rAAAs should be tailored to these results. Device and technique modifications are necessary to increase the applicability of EVAR for rAAAs.
Annals of Vascular Surgery 11/2008; 22(6):716-22. · 1.03 Impact Factor
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ABSTRACT: Children less than 2 years of age are capable of healing large calvarial defects, whereas adults have been found to lack this endogenous ability. In this study, we used microarray analysis to compare genomewide expression patterns during active regeneration after injury with calvaria in skeletally immature and mature mice. Parietal bone defects were created in 6-day-old (juvenile) and 60-day-old (adult) mice using a 4-mm trephine bit (n = 20 mice per age group). The calvarial disc was removed, leaving the underlying dura mater intact. Two weeks after injury, the region of regeneration with the underlying dura mater was harvested, and RNA was extracted for microarray analysis. The 25 most differentially upregulated genes in juvenile regenerates compared with adults were listed, as well as selected bone-related genes. In addition, QRT-PCR confirmation of specific genes was performed for validation. Juvenile regenerates expressed significantly greater amounts of BMP-2, -4, -7, as well as FGF-2 and its receptor FGFR-1. Various other growth factors were also noted to be upregulated, including IGF-2 and Ptn. This corresponded with the increased expression of markers for osteogenic differentiation of Sparc and Oc. Markers of osteoclast activity, Acp5, Ctsk, and Mmp2, were noted to be greater in juvenile regenerates compared with adults. The observation of Mmp14 upregulation, however, highlights the importance of balanced osteoclast-mediated bone resorption for ultimate healing. The 2 most differentially regulated genes, transthyretin (Ttr) and prostaglandin D2 synthase (Ptgds), highlight the potential role of retinoic acid signaling and the prostaglandin axis on skeletal regeneration. These findings underscore the multitude of biomolecular mechanisms at play, allowing juvenile calvaria to heal after injury. The identification of various growth factors and cytokines involved also suggests novel therapeutic strategies for tissue-engineering purposes.
The Journal of craniofacial surgery 10/2008; 19(5):1292-301. · 0.81 Impact Factor
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ABSTRACT: Skeletal defects represent a significant socioeconomic burden to the US healthcare system. Current options for reconstructing osseous deficits have shortcomings.
To review the use of mesenchymal stem cells for skeletal tissue engineering.
We focused on the application of mesenchymal cells in skeletal regeneration, optimization of this technique, tropic effects of multipotent mesenchymal cells, and future directions.
A number of cell-based modalities have been investigated. We have been interested in the role of adipose-derived stromal cells in bone regeneration and understanding the mechanisms behind osteogenic differentiation of progenitor cells and acceleration of this process. Future clinical applications of multipotent mesenchymal cells will depend on better understanding of the molecular signaling involved in osteogenic differentiation and maintaining pluripotency.
Expert opinion on biological therapy 08/2008; 8(7):885-93. · 3.22 Impact Factor
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ABSTRACT: Craniosynostosis is a relatively common developmental disorder that leads to a number of serious consequences. Previous studies have shown the influence of dura mater on the overlying cranial suture. This study was conducted to determine the role of regional dura mater versus the intrinsic nature of the suture in directing the overlying suture's fate.
The authors examined the effect of regional dura mater on the fate and morphology of the posterofrontal and coronal sutures. In 8-day-old Sprague-Dawley rats, calvarial disks, consisting of the posterofrontal and coronal sutures, were excised and placed in one of three positions: (1) native position (control group), (2) rotated 45 degrees, or (3) rotated 90 degrees (n = 5 animals per group). The animals were euthanized 1 month postoperatively, and the sutures were analyzed histologically.
The control group revealed normal suture morphology (n = 5). In the 45-degree rotation group, which placed the posterofrontal and coronal sutures over non-suture-associated dura mater, the posterofrontal sutures fused with thin morphology, and the coronal sutures remained patent (n = 5). In the 90-degree rotation group, the posterofrontal sutures, which were positioned over coronal suture-associated dura mater, were found to be fused with thinner morphology. The coronal sutures of the 90-degree rotation group, which were placed over posterofrontal suture-associated dura mater, remained patent but had acquired a posterofrontal-like morphology (n = 5).
This study further elucidates variations in the biology of dura mater, depending on its location. Furthermore, these results illustrate the interplay between regional dura mater and the inherent characteristics of the suture complex in determining suture biology.
Plastic and reconstructive surgery 08/2008; 122(1):77-84. · 2.74 Impact Factor
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ABSTRACT: Craniosynostosis, the premature fusion of cranial sutures, results in serious neurologic and morphologic abnormalities when left untreated. Surgical excision of the fused sutures and remodeling of the skull remains the standard therapy. Development of novel, minimally invasive therapies for craniosynostosis will undoubtedly be dependent on a more thorough understanding of the molecular mechanisms underlying this abnormality. Significant evidence suggests the influence of regional dura mater on the behavior of the overlying suture complex. The mouse model has been instrumental in investigating this observation because of the natural juxtaposition of the posterior frontal suture, which fuses early in life, with the other cranial sutures, which remain patent.
The authors used microarray analysis to compare genomic changes in the dura mater underlying the posterior frontal and sagittal sutures of mice. Suture-associated dura mater was harvested from mice before (postnatal day 5), during (postnatal day 10), and after (postnatal day 20) posterior frontal suture fusion (n = 20 mice for each of the three time points).
Microarray results confirmed differential regulation of genes involved in paracrine signaling, extracellular matrix, and bone remodeling between the dura mater underlying the fusing posterior frontal suture and the patent sagittal suture.
These data confirm global differences in gene expression between regional dura mater underlying fusing and patent sutures. These results provide further insight into potential molecular mechanisms that may play a role in cranial suture biology.
Plastic and reconstructive surgery 08/2008; 122(2):389-99. · 2.74 Impact Factor
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ABSTRACT: Contributions from multidisciplinary investigations have focused attention on the potential of tissue engineering to yield novel therapeutics. Congenital malformations, including cleft palate, craniosynostosis, and craniofacial skeletal hypoplasias represent excellent targets for the implementation of tissue engineering applications secondary to the technically challenging nature and inherent inadequacies of current reconstructive interventions. Apropos to the search for answers to these clinical conundrums, studies have focused on elucidating the molecular signals driving the biologic activity of the aforementioned maladies. These investigations have highlighted multiple signaling pathways, including Wnt, fibroblast growth factor, transforming growth factor-beta, and bone morphogenetic proteins, that have been found to play critical roles in guided tissue development. Furthermore, a comprehensive knowledge of these pathways will be of utmost importance to the optimization of future cell-based tissue engineering strategies. The scope of this review encompasses a discussion of the molecular biology involved in the development of cleft palate and craniosynostosis. In addition, we include a discussion of craniofacial distraction osteogenesis and how its applied forces influence cell signaling to guide endogenous bone regeneration. Finally, this review discusses the future role of cell-based tissue engineering in the treatment of congenital malformations.
Pediatric Research 06/2008; 63(5):545-51. · 2.70 Impact Factor
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ABSTRACT: Craniosynostosis, or the premature fusion of one or more cranial sutures, is a relatively common congenital defect that causes a number of morphologic and functional abnormalities. With advances in genetics and molecular biology, research of craniosynostosis has progressed from describing gross abnormalities to understanding the molecular interactions that underlie these cranial deformities. Animal models have been extremely valuable in improving our comprehension of human craniofacial morphogenesis, primarily by human genetic linkage analysis and the development of knock-out animals. This article provides a brief review of perisutural tissue interactions, embryonic origins, signaling molecules and their receptors, and transcription factors in maintaining the delicate balance between proliferation and differentiation of cells within the suture complex that determines suture fate. Finally, this article discusses the potential implications for developing novel therapies for craniosynostosis.
Plastic and reconstructive surgery 05/2008; 121(4):170e-8e. · 2.74 Impact Factor
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ABSTRACT: Skeletal deficits represent a substantial biomedical burden on the US healthcare system. Current strategies for reconstructing bony defects are fraught with inadequacies. Cell-based therapies for skeletal regeneration offer a paradigm shift that may provide alternative solutions. Substantial work has identified a host of cellular sources that possess the potential for osteogenic differentiation. Significant efforts have been devoted toward characterizing the role of postnatal cellular sources that are relatively abundant and easily accessible. Among these, the potential of using adipose-derived stromal cells for skeletal regeneration has garnered much interest. Integral to these efforts directed at characterizing cellular sources are studies that seek to understand the factors that initiate and regulate osteogenic differentiation of progenitor cells. Specifically, focus has been directed on elucidating the role of bone morphogenetic protein and fibroblast growth factor signaling in regulating osteogenic differentiation of osteoprogenitor cells. Concurrent studies in the field of scaffold design have also helped to advance the potential for cell-based therapies.
Human Molecular Genetics 04/2008; 17(R1):R93-8. · 7.64 Impact Factor
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ABSTRACT: Calvarial bone defects are a common clinical scenario in craniofacial surgery. Numerous approaches are used to reconstruct skull defects, and each possesses its own inherent disadvantages. This fact underscores the opportunity to develop a novel method to repair osseous defects in craniofacial surgery. Recent literature strongly suggests that cell-based therapies in the form of regenerative medicine may be a developing paradigm in reconstructive surgery. Although numerous studies have probed osteoprogenitor cells from mice, few have explored the biology of human cells in the setting of osteogenesis in an equally rigorous manner. This study proposes a nude mouse model of critical-sized calvarial defects to study the in vivo biology of human osteoprogenitor cells. Critical-sized 4.0-mm calvarial defects were created in nude mice (n = 15) with a custom trephine drill bit outfitted to a dental drill handpiece. During the craniotomy, the dura mater was spared from injury. Gross inspection, routine histology, and micro-computed tomographic scanning were performed at 2, 4, 8, and 16 weeks postoperatively. There was no calvarial healing in any of the animals by 16 weeks. The dura mater remained intact in all subjects. Gross, histologic, and radiographic assays confirmed these findings. Although several studies have implanted human osteoprogenitor cells in vivo in various animal models, few have documented the appropriate controls or conditions necessary to support the potential to translate benchtop findings into clinical applications. We propose in this study that the nude mouse critical-sized calvarial defect model will be valuable with increasing investigations with human osteoprogenitor cells.
Journal of Craniofacial Surgery 02/2008; 19(1):192-7. · 0.82 Impact Factor
