Application of skeletal buttress analogy in composite facial reconstruction.
Ontology highlight
ABSTRACT:
SUBMITTER: Bluebond-Langner R
PROVIDER: S-EPMC3052649 | biostudies-other | 2009 Mar
REPOSITORIES: biostudies-other
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Project description:Head and neck cancer is often diagnosed at advanced stages, and surgical resection with wide margins is generally indicated, despite this treatment being associated with poor postoperative quality of life (QOL). We have previously reported on the therapeutic effects of skeletal muscle-derived multipotent stem cells (Sk-MSCs), which exert reconstitution capacity for muscle-nerve-blood vessel units. Recently, we further developed a 3D patch-transplantation system using Sk-MSC sheet-pellets. The aim of this study is the application of the 3D Sk-MSC transplantation system to the reconstitution of facial complex nerve-vascular networks after severe damage. Mouse experiments were performed for histological analysis and rats were used for functional examinations. The Sk-MSC sheet-pellets were prepared from GFP-Tg mice and SD rats, and were transplanted into the facial resection model (ST). Culture medium was transplanted as a control (NT). In the mouse experiment, facial-nerve-palsy (FNP) scoring was performed weekly during the recovery period, and immunohistochemistry was used for the evaluation of histological recovery after 8 weeks. In rats, contractility of facial muscles was measured via electrical stimulation of facial nerves root, as the marker of total functional recovery at 8 weeks after transplantation. The ST-group showed significantly higher FNP (about three fold) scores when compared to the NT-group after 2-8 weeks. Similarly, significant functional recovery of whisker movement muscles was confirmed in the ST-group at 8 weeks after transplantation. In addition, engrafted GFP+ cells formed complex branches of nerve-vascular networks, with differentiation into Schwann cells and perineurial/endoneurial cells, as well as vascular endothelial and smooth muscle cells. Thus, Sk-MSC sheet-pellet transplantation is potentially useful for functional reconstitution therapy of large defects in facial nerve-vascular networks.
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Project description:We describe comparative patch analysis for modeling the structures of multidomain proteins and protein complexes, and apply it to the PSD-95 protein. Comparative patch analysis is a hybrid of comparative modeling based on a template complex and protein docking, with a greater applicability than comparative modeling and a higher accuracy than docking. It relies on structurally defined interactions of each of the complex components, or their homologs, with any other protein, irrespective of its fold. For each component, its known binding modes with other proteins of any fold are collected and expanded by the known binding modes of its homologs. These modes are then used to restrain conventional molecular docking, resulting in a set of binary domain complexes that are subsequently ranked by geometric complementarity and a statistical potential. The method is evaluated by predicting 20 binary complexes of known structure. It is able to correctly identify the binding mode in 70% of the benchmark complexes compared with 30% for protein docking. We applied comparative patch analysis to model the complex of the third PSD-95, DLG, and ZO-1 (PDZ) domain and the SH3-GK domains in the PSD-95 protein, whose structure is unknown. In the first predicted configuration of the domains, PDZ interacts with SH3, leaving both the GMP-binding site of guanylate kinase (GK) and the C-terminus binding cleft of PDZ accessible, while in the second configuration PDZ interacts with GK, burying both binding sites. We suggest that the two alternate configurations correspond to the different functional forms of PSD-95 and provide a possible structural description for the experimentally observed cooperative folding transitions in PSD-95 and its homologs. More generally, we expect that comparative patch analysis will provide useful spatial restraints for the structural characterization of an increasing number of binary and higher-order protein complexes.
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Project description:ImportanceResearch in facial aging has focused on soft-tissue changes rather than bony changes despite evidence of the importance of underlying bony structural changes. Research has also been limited by comparing different patients in separate age groups rather than the same patients over time.ObjectiveTo longitudinally document patterns of change in the facial skeleton and determine a consistent methodology for measuring these changes.Design, setting, and participantsCase series study of university hospital system records using facial computed tomographic (CT) images timed at least 8 years apart in adults initially aged 40 to 55 years with no history of facial surgery who required repeated facial imaging that included the entire midface and cranium.Main outcomes and measuresFace CTs were analyzed for 3-dimensional constructions and 2-dimensional measurements to document changes in glabellar, piriform, and maxillary angles and piriform height and width.ResultsFourteen patients (5 men, 9 women; mean [SD] age, 51.1 [5.8] years) with mean (SD) follow-up of 9.7 (1.4) years were eligible for 2-dimensional analysis, which revealed statistically significant decreases in mean (SD) glabellar angles (from 68.8° [7.6°] to 66.5° [8.6°]) and maxillary angles on both the right (from 82.5° [6.3°] to 81.0° [7.1°]) and left (from 83.0° [5.8°] to 81.0° [7.0°]), as well as increases in mean (SD) piriform width (from 24.5 [1.6] mm to 25.5 [1.3] mm). Nine patients (3 men, 6 women; mean [SD] age, 51.4 [6.3] years) with mean (SD) follow-up imaging at 9.6 (1.5) years were eligible for 3-dimensional analysis, which revealed statistically significant decreases in mean (SD) maxillary angles (from 56.5° [6.6°] to 51.6° [7.6°]) and piriform angles (from 50.8° [3.4°] to 49.1° [3.4°]). Statistically significant differences between the sexes were also noted: Initial mean (SD) glabellar angle for men was 61.7° (5.7°) vs 72.7° (5.4°) for women, with final values of 57.9° (4.9°) vs 71.2° (6.0°). Mean (SD) maxillary angle initial values were 87.8° (6.1°) (right) and 87.1° (4.9°) (left) for men, with 79.6° (4.3°) and 80.6° (5.0°) for women, respectively. Final values were 87.0° (4.4°) and 86.9° (4.1°) for men and 77.7° (6.1°) and 77.7° (6.2°) for women, respectively. Mean (SD) piriform height for men was 35.0 (2.0) mm initially and 35.5 (2.1) mm finally, vs 31.3 (2.8) and 31.6 (3.0) mm for women, respectively.Conclusions and relevanceOur pilot study of repeated CT images of patients over several years supports previous studies of bony facial aging and further characterizes these changes. This study is the first, to our knowledge, to document bony changes of the face in the same group of patients at different time points to better characterize facial aging. We also detail an improved methodology to study bony aging to contribute to additional research in the field.Level of evidenceNA.
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Project description:Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care-the use of bone harvested from another region in the body-has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, native bovine bone matrix, and a perfusion bioreactor for the growth and transport of living grafts, without bone morphogenetic proteins. The ramus-condyle unit, the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatán minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material and crafted it into an anatomically correct shape using image-guided micromilling to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either nonseeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering.
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Project description:The management of blast and burn injuries to the facial soft tissue and craniomaxillofacial skeleton has been a challenge since the inception of reconstructive plastic surgery. These injuries continue to present complex reconstructive challenges today. While there have been advancements in free tissue transfer and vascularized composite allotransplantation, prosthetics have been used successfully since antiquity until the present day. Prosthetics may achieve acceptable coverage without complex surgery or as an adjunct to reconstructive surgery. Here, we report a case of devastating blast injury to the face that has been managed successfully with orbital prosthetics anchored with osseointegrated implants.
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Project description:Visual memory for faces has been extensively researched, especially regarding the main factors that influence face memorability. However, what we remember exactly about a face, namely, the pictorial content of visual memory, remains largely unclear. The current work aims to elucidate this issue by reconstructing face images from both perceptual and memory-based behavioural data. Specifically, our work builds upon and further validates the hypothesis that visual memory and perception share a common representational basis underlying facial identity recognition. To this end, we derived facial features directly from perceptual data and then used such features for image reconstruction separately from perception and memory data. Successful levels of reconstruction were achieved in both cases for newly-learned faces as well as for familiar faces retrieved from long-term memory. Theoretically, this work provides insights into the content of memory-based representations while, practically, it may open the path to novel applications, such as computer-based 'sketch artists'.
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Project description:Facial flatness indices have been used in anthropology to discern differences among populations. They were evaluated on skulls from around the world.Aims(1) to evaluate the use of facial flatness indices in orthodontics and (2) to assess their variation among malocclusions, age and sex.Materials and methodsA total of 322 cone beam computed tomography radiographs were digitized and three facial indices (frontal, simotic and zygomaxillary) along with three transverse distances (fmo1-fmo2, zma1-zma2 and n1-n2) were assessed and compared between different groups.ResultsThe zygomaxillary index was increased in Class II (32.6 ± 0.42; p < 0.001) and decreased in Class III malocclusions (29.4 ± 0.66; p < 0.001) compared to Class I (31.18 ± 0.3; p < 0.001). The frontal and nasal flatness are not characteristic features of any of the sagittal malocclusions. Facial flatness indices did not differ between males and females and between growing and non-growing patients.ConclusionThe position of subspinale point (A point) forward or backward relative to the zygomaxillary width is a factor of assessment of facial flatness. The zygomaxillary index could be helpful in weighting proportionally the width of the maxilla (expansion) relative to its sagittal position in Class II and Class III malocclusions.
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Project description:Patterning of the facial skeleton involves the precise deployment of thousands of genes in distinct regions of the pharyngeal arches. Despite the significance for craniofacial development, how genetic programs drive this regionalization remains incompletely understood. Here we use combinatorial labeling of zebrafish cranial neural crest-derived cells (CNCCs) to define global gene expression along the dorsoventral axis of the developing arches. Intersection of region-specific transcriptomes with expression changes in response to signaling perturbations demonstrates complex roles for Endothelin 1 (Edn1) signaling in the intermediate joint-forming region, yet a surprisingly minor role in ventralmost regions. Analysis of co-variance across multiple sequencing experiments further reveals clusters of co-regulated genes, with in situ hybridization confirming the domain-specific expression of novel genes. We then created loss-of-function alleles for 12 genes and uncovered antagonistic functions of two new Edn1 targets, follistatin a (fsta) and emx2, in regulating cartilaginous joints in the hyoid arch. Our unbiased discovery and functional analysis of genes with regional expression in zebrafish arch CNCCs reveals complex regulation by Edn1 and points to novel candidates for craniofacial disorders.
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