Lung on Chip: In vitro HGF effects on injured alveolar A549 epithelial cells in microfluidic system

Microfluidic systems have become competitive tools in the invitro modelling of diseases and promising alternatives to animal studies. They allow obtaining more invivo like conditions for cellular assays. Research in idiopathic pulmonary fibrosis could benefit from this novel methodological approach to understand the pathophysiology of the disease & develop efficient therapies. The use of hepatocyte growth factor (HGF) for alveolar reepithelisation is a promising approach. In this study, we show a new microfluidic system to analyse the effects of HGF on injured alveolar epithelial cells. Microfluidic systems in polydimethylsiloxane were fabricated by soft lithography. The alveolar A549 epithelial cells (10,000 cells) were seeded and studied in these microfluidic systems with media perfusion (1μl/30min). Injury tests were made on the cells by the perfusion with media containing H2O2 or bleomycin. The degree of injury was then assessed by a metabolic and an apoptotic assays. Wound assays were also performed with a central laminar flow of trypsin. Monitoring of wound closure with HGF vs control media was assessed. The alveolar A549 epithelial cells grew and proliferated in the microfluidic system. In the wound closure assay, the degree of wound closure after 5 hours was (53.3±1.3%) with HGF compared to (9.8±2.4%) without HGF (P <0.001). We present a novel microfluidic model that allows culture, injury and wounding of A549 epithelial cells and represents the first step towards the development of an invitro reconstitution of the alveolar-capillary interface. We were also able to confirm that HGF increased alveolar epithelial repair in this system.

Lung on a chip: Co-culture of alveolar epithelial cells and bone marrow derived stromal stem cells in a microfluidic system

Background: Microfluidics system are novel tools to study cell-cell interactions in vitro. This project focuses on the development of a new microfluidic device to co-culture alveolar epithelial cells and mesenchymal stem cells to study cellular interactions involved in healing the injured alveolar epithelium. Methods: Microfluidic systems in polydimethylsiloxane were fabricated by soft lithography. The alveolar A549 epithelial cells were seeded and injury tests were made on the cells by perfusion with media containing H2O2 or bleomycin during 6 or 18hrs. Rat Bone marrow derived stromal cells (BMSC) were then introduced into the system and cell-cell interaction was studied over 24 hrs. Results: A successful co-culture of A549 alveolar epithelial cells and BMS was achieved in the microfluidic system. The seeded alveolar epithelial cells and BMSC adhered to the bottom surface of the microfluidic device and proliferated under constant perfusion. Epithelial injury to mimic mechanisms seen in idiopathic pulmonary fibrosis was induced in the microchannels by perfusing with H2O2 or bleomycin. Migration of BMSC towards the injured epithelium was observed as well as cell-cell interaction between the two cell types was also seen. Conclusion: We demonstrate a novel microfluidic device aimed at showing interactions between different cell types on the basis of a changing microenvironment. Also we were able to confirm interaction between injured alvolar epithelium and BMSC, and showed that BMSC try to heal the injured epitelium.

Soft tissue profile changes after bilateral sagittal split osteotomy for mandibular setback: a systematic review

PURPOSE: To evaluate the ratio of soft tissue to hard tissue in bilateral sagittal split setback osteotomy with rigid internal fixation or wire fixation. MATERIALS AND METHODS: A literature search was performed using PubMed, Medline, CINAHL, Web of Science, the Cochrane Library, and Google Scholar Beta. From the original 766 articles identified, 8 articles were included. Two articles were prospective and 6 retrospective. The follow-up period ranged from 1 year to 12.7 years for rigid internal fixation. Two articles on wire fixation were found to be appropriate for inclusion. RESULTS: The differences between short- and long-term ratios of the lower lip to lower incisors for bilateral sagittal split setback osteotomy with rigid internal fixation or wire fixation were quite small. The ratio was 1:1 in the long term and by trend slightly lower in the short term. No distinction was seen between the short- and long-term ratios for mentolabial fold. The ratio was found to be 1:1 for the mentolabial fold to point B. In the short term, the ratio of the soft tissue pogonion to the pogonion showed a 1:1 ratio, with a trend to be lower in the long term. The upper lip showed mainly protrusion, but the amount was highly variable. CONCLUSIONS: This systematic review shows that evidence-based conclusions on soft tissue changes are difficult to draw. This is mostly because of inherent problems of retrospective studies, inferior study designs, and the lack of standardized outcome measurements. Well-designed prospective studies with sufficient samples and excluding additional surgery, ie, genioplasty or maxillary surgery, are needed.

Soft tissue profile changes after bilateral sagittal split osteotomy for mandibular advancement: a systematic review

PURPOSE: The purpose of the present systematic review was to evaluate the soft tissue/hard tissue ratio in bilateral sagittal split advancement osteotomy (BSSO) with rigid internal fixation (RIF) or wire fixation (WF). MATERIALS AND METHODS: The databases PubMed, Medline, CINAHL, Web of Science, Cochrane Library, and Google Scholar Beta were searched. From the original 711 articles identified, 12 were finally included. Only 3 studies were prospective and 9 were retrospective. The postoperative follow-up ranged from 3 months to 12.7 years for RIF and 6 months to 5 years for WF. RESULTS: The short- and long-term ratios for the lower lip to lower incisor for BSSO with RIF or WF were 50%. No difference between the short- and long-term ratios for the mentolabial-fold to point B and soft tissue pogonion to pogonion could be observed. It was a 1:1 ratio. One exception was seen for the long-term results of the soft tissue pogonion to pogonion in BSSO with RIF; they tended to be greater than a 1:1 ratio. The upper lip mainly showed retrusion but with high variability. CONCLUSIONS: Despite a large number of studies on the short- and long-term effects of mandibular advancement by BSSO, the results of the present systematic review have shown that evidence-based conclusions on soft tissue changes are still unknown. This is mostly because of the inherent problems of retrospective studies, inferior study designs, and the lack of standardized outcome measures. Well-designed prospective studies with sufficient sample sizes that have excluded patients undergoing additional surgery (ie, genioplasty or maxillary surgery) are needed.

Anatomically-Driven Soft-Tissue Simulation Strategy for Cranio-Maxillofacial Surgery Using Facial Muscle Template Model

We propose a computationally efficient and biomechanically relevant soft-tissue simulation method for cranio-maxillofacial (CMF) surgery. A template-based facial muscle reconstruction was introduced to minimize the efforts on preparing a patient-specific model. A transversely isotropic mass-tensor model (MTM) was adopted to realize the effect of directional property of facial muscles in reasonable computation time. Additionally, sliding contact around teeth and mucosa was considered for more realistic simulation. Retrospective validation study with postoperative scan of a real patient showed that there were considerable improvements in simulation accuracy by incorporating template-based facial muscle anatomy and sliding contact.

The effect of different implant neck configurations on soft and hard tissue healing: a randomized-controlled clinical trial

Objective: To compare the soft and hard tissue healing and remodeling around tissue-level implants with different neck configurations after at least 1 year of functional loading. Material and methods: Eighteen patients with multiple missing teeth in the posterior area received two implants inserted in the same sextant. One test (T) implant with a 1.8 mm turned neck and one control (C) implant with a 2.8 mm turned neck were randomly assigned. All implants were placed transmucosally to the same sink depth of approximately 1.8 mm. Peri-apical radiographs were obtained using the paralleling technique and digitized. Two investigators blinded to the implant type-evaluated soft and hard tissue conditions at baseline, 6 months and 1 year after loading. Results: The mean crestal bone levels and soft tissue parameters were not significantly different between T and C implants at all time points. However, T implants displayed significantly less crestal bone loss than C implants after 1 year. Moreover, a frequency analysis revealed a higher percentage (50%) of T implants with crestal bone levels 1–2 mm below the implant shoulder compared with C implants (5.6%) 1 year after loading. Conclusion: Implants with a reduced height turned neck of 1.8 mm may, indeed, lower the crestal bone resorption and hence, may maintain higher crestal bone levels than do implants with a 2.8 mm turned neck, when sunk to the same depth. Moreover, several factors other than the vertical positioning of the moderately rough SLA surface may influence crestal bone levels after 1 year of function.

Toward clinical X-ray phase-contrast CT: demonstration of enhanced soft-tissue contrast in human specimen

X-ray computed tomography (CT) using phase contrast can provide images with greatly enhanced soft-tissue contrast in comparison to conventional attenuation-based CT. We report on the first scan of a human specimen recorded with a phase-contrast CT system based on an x-ray grating interferometer and a conventional x-ray tube source. Feasibility and potential applications of preclinical and clinical phase-contrast CT are discussed.

Soft-Tissue Simulation for Cranio-Maxillofacial Surgery: Clinical Needs and Technical Aspects

Computerized soft-tissue simulation can provide unprecedented means for predicting facial outlook pre-operatively. Surgeons can virtually perform several surgical plans to have the best surgical results for their patients while considering corresponding soft-tissue outcome. It could be used as an interactive communication tool with their patients as well. There has been comprehensive amount of works for simulating soft-tissue for cranio-maxillofacial surgery. Although some of them have been realized as commercial products, none of them has been fully integrated into clinical practice due to the lack of accuracy and excessive amount of processing time. In this chapter, state-of-the-art and general workflow in facial soft-tissue simulation will be presented, along with an example of patient-specific facial soft-tissue simulation method.

18F-fluorodeoxyglucose uptake of bone and soft tissue sarcomas in pediatric patients

A high (18)F-fluorodeoxyglucose (FDG) uptake by positron emission tomography/computed tomography (PET/CT) imaging in sarcomas of adults has been reported. The current study aimed at defining the degree of (18)F-FDG uptake of pediatric sarcomas. This retrospective study included 29 patients (23 males, 6 females; mean age 14 ± 5 years) with soft tissue (n = 9) or bone (n = 20) sarcomas. Twenty-two patients (76%) underwent (18)F-FDG PET/CT and 7 (24%) had dedicated (18)F-FDG PET studies. Tumor (18)F-FDG uptake was quantified by standard uptake value (SUV)(max) and tumor-to-liver ratios (SUV ratios; tumor SUV(max)/liver SUV(mean)). Tumor SUV(max) and SUV ratios were correlated with tumor Ki-67 expression. SUV(max) ranged from 1.4 to 24 g/mL (median 2.5 g/mL) in soft tissue sarcomas and 1.6 to 20.4 g/mL (median 6.9 g/mL) in bone sarcomas (P = .03), and from 1.6 to 9.2 g/mL (median 3.9 g/mL) and 3.5 to 20.4 g/mL (median 12 g/mL) in Ewing sarcoma and osteosarcoma, respectively (P = .009). Tumor SUV ratios ranged from 0.8 to 8.7 (median 1.9) in soft tissue sarcomas and 1.4 to 8.9 (median 3.8) in bone sarcomas (P = .08). Ewing sarcoma had a significantly lower tumor SUV ratio than osteosarcoma (P = .01). Ki-67 expression correlated significantly with the (18)F-FDG uptake in bone but not in soft tissue sarcomas. All sarcomas were visualized by (18)F-FDG PET/CT imaging. A higher (18)F-FDG uptake was observed in osteosarcoma than in Ewing and soft tissue sarcomas. The results of this study suggest that the degree of tumor (18)F-FDG uptake is sufficient to allow for monitoring of therapeutic responses in pediatric sarcomas.

A navigation system for percutaneous needle interventions based on PET/CT images: design, workflow and error analysis of soft tissue and bone punctures

Percutaneous needle intervention based on PET/CT images is effective, but exposes the patient to unnecessary radiation due to the increased number of CT scans required. Computer assisted intervention can reduce the number of scans, but requires handling, matching and visualization of two different datasets. While one dataset is used for target definition according to metabolism, the other is used for instrument guidance according to anatomical structures. No navigation systems capable of handling such data and performing PET/CT image-based procedures while following clinically approved protocols for oncologic percutaneous interventions are available. The need for such systems is emphasized in scenarios where the target can be located in different types of tissue such as bone and soft tissue. These two tissues require different clinical protocols for puncturing and may therefore give rise to different problems during the navigated intervention. Studies comparing the performance of navigated needle interventions targeting lesions located in these two types of tissue are not often found in the literature. Hence, this paper presents an optical navigation system for percutaneous needle interventions based on PET/CT images. The system provides viewers for guiding the physician to the target with real-time visualization of PET/CT datasets, and is able to handle targets located in both bone and soft tissue. The navigation system and the required clinical workflow were designed taking into consideration clinical protocols and requirements, and the system is thus operable by a single person, even during transition to the sterile phase. Both the system and the workflow were evaluated in an initial set of experiments simulating 41 lesions (23 located in bone tissue and 18 in soft tissue) in swine cadavers. We also measured and decomposed the overall system error into distinct error sources, which allowed for the identification of particularities involved in the process as well as highlighting the differences between bone and soft tissue punctures. An overall average error of 4.23 mm and 3.07 mm for bone and soft tissue punctures, respectively, demonstrated the feasibility of using this system for such interventions. The proposed system workflow was shown to be effective in separating the preparation from the sterile phase, as well as in keeping the system manageable by a single operator. Among the distinct sources of error, the user error based on the system accuracy (defined as the distance from the planned target to the actual needle tip) appeared to be the most significant. Bone punctures showed higher user error, whereas soft tissue punctures showed higher tissue deformation error.

Combined bone and soft-tissue augmentation surgery in temporo-orbital contour reconstruction

Temporal hollowing due to temporal muscle atrophy after standard skull base surgery is common. Various techniques have been previously described to correct the disfiguring defect. Most often reconstruction is performed using freehand molded polymethylmethacrylate cement. This method and material are insufficient in terms of aesthetic results and implant characteristics. We herein propose reconstruction of such defects with a polyetheretherketone (PEEK)-based patient-specific implant (PSI) including soft-tissue augmentation to preserve normal facial topography. We describe a patient who presented with a large temporo-orbital hemangioma that had been repaired with polymethylmethacrylate 25 years earlier. Because of a toxic skin atrophy fistula, followed by infection and meningitis, this initial implant had to be removed. The large, disfiguring temporo-orbital defect was reconstructed with a PEEK-based PSI. The lateral orbital wall and the temporal muscle atrophy were augmented with computer-aided design and surface modeling techniques. The operative procedure to implant and adopt the reconstructed PEEK-based PSI was simple, and an excellent cosmetic outcome was achieved. The postoperative clinical course was uneventful over a 5-year follow-up period. Polyetheretherketone-based combined bony and soft contour remodeling is a feasible and effective method for cranioplasty including combined bone and soft-tissue reconstruction of temporo-orbital defects. Manual reconstruction of this cosmetically delicate area carries an exceptional risk of disfiguring results. Augmentation surgery in this anatomic location needs accurate PSIs to achieve satisfactory cosmetic results. The cosmetic outcome achieved in this case is superior compared with previously reported techniques.