Radioactive nanosized colloids and indocyanine green identify the same sentinel lymph nodes in oral squamous cell carcinoma.

PURPOSE: Near-infrared fluorescence imaging using indocyanine green (ICG) combined with radioactive markers has the potential to improve sentinel lymph-node (SLN) mapping in oral squamous cell carcinoma (OSCC). This study aimed to evaluate the ability of 99mTc and ICG in identifying the sentinel lymph nodes in patients with early stage OSCC. METHODS: Data were collected prospectively, and a retrospective analysis of 15 patients with early stage OSCC and a cN0 neck was performed. All patients received peritumoral injection of 99mTc the day before surgery and ICG was administered intraoperatively. Intentionally, the application of the two different tracers were done by two different physicians with varying degrees of experience. The number of identified lymph nodes positive for 99mTc and ICG, the overlap or possible discrepancies of both methods, and the time until fluorescence signals of ICG were detected were noted. RESULTS: In all patients, a 100% agreement in sentinel lymph-node identification was achieved, regardless of both the exact location of the peritumoral injection and the experience of the injecting surgeon. Time until ICG accumulation in the sentinel lymph node was consistently found to be between 1 and 3 min. CONCLUSION: ICG constitutes a viable and useful addition to 99mTc for intraoperative sentinel lymph-node detection in this study.

Meeting Quality Metrics in Oral Squamous Cell Carcinoma Surgery: A Single-Center Experience.

Patient-centered quality metrics have been proposed to evaluate and optimize hospital processes, aiming to improve patient outcomes. Furthermore, they can be used to objectively rate and compare the ability of health care providers to meet the needs of their patients. In patients with advanced resectable oral squamous cell carcinoma, optimal surgical treatment of the neck and timely initiation of both surgical and adjuvant therapy, when indicated, are crucial for recurrence-free and overall survival. This retrospective analysis included 160 patients who received primary resection of oral squamous cell carcinoma and concurrent neck dissection. It aimed to investigate how well quality metrics were met during a 6-year period in the department of oral and maxillofacial surgery at a university hospital. 93.1% of patients were seen in the specialist's office within 21 days after referral. Resection was classified as R0 in 94.4%. A lymph node yield ≥ 18 was achieved in 82.5%. The lymph node ratio was ≤6% in 43.3% of nodal-positive necks. Readmission and unplanned revision surgery were rare (6.9%). Adjuvant radiotherapy was started ≤ 6 weeks after surgery in 45.3%, and the indication was in accordance with international guidelines in all cases. Quality metrics are an effective tool for planning process optimization in a hospital. Moreover, nodal quality metrics such as lymph node yield and lymph node ratio could, after validation, complement existing and well-established prognostic parameters for patient-specific adaptation of adjuvant treatment plans.

[A radiolucent rarity - primary intraosseous mucoepidermoid carcinoma of the posterior mandible: From radiographic incidental finding to molecular pathological diagnosis]. / Eine radioluzente Rarität ­ Primär intraossäres Mukoepidermoidkarzinom des posterioren Unterkiefers: vom röntgenologischen Zufallsbefund zur molekularpathologischen Diagnose.

We report the case of a 64-year-old patient with incidental finding of a unilocular radiolucency in the posterior mandible on an apical radiograph. The biopsy (cystostomy) revealed the unusual finding of a primary intraosseous mucoepidermoid carcinoma; this is with 2­4% of ectopic manifestations of this entity a rarity. Molecular pathological analysis with a specific panel (SalvGlandDx) and FISH provided diagnosis-confirming evidence of the specific CRTC1-MAML2 fusion. Box resection, prophylactic osteosynthesis using a patient-specific reconstruction plate, neck dissection, and local coverage using a Bichat flap were performed according to the interdisciplinary tumor board decision. With tumor-free lymph nodes and R0 resection, adjuvant therapy was not required. Clinical and imaging follow-up over 24 months showed no evidence of locoregional recurrence. The presented case report emphasizes the central role of private dental practices in the early detection of oral malignancies. These should always be considered in the differential diagnosis of cystic lesions.

Proximity of the middle meningeal artery and maxillary artery to the mandibular head and mandibular neck as revealed by three-dimensional time-of-flight magnetic resonance angiography.

PURPOSE: The close topographic relationship between vascular and osseous structures in the condylar and subcondylar region and marked variability in the arterial course has been revealed by both imaging and cadaveric studies. This study aimed to verify the previously published information in a large sample and to determine a safe surgical region. METHODS: We analyzed the three-dimensional time-of-flight magnetic resonance angiography images of 300 individuals. RESULTS: The mean distance between the middle meningeal artery and the apex of the condyle or the most medial point of the condyle was 18.8 mm (range: 11.2-25.9 mm) or 14.5 mm (range: 8.8-22.9 mm) respectively. The course of the maxillary artery relative to the lateral pterygoid muscle was medial in 45.7% of cases and lateral in 54.3%. An asymmetric course was evident in 66 patients (22%). The mean distance between the maxillary artery and condylar process at the deepest point of the mandibular notch was 6.2 mm in sides exhibiting a medial course (range: 3.7-9.8 mm) and 6.6 mm in sides exhibiting a lateral course (range: 3.9-10.4 mm). The distances were significantly influenced by age, gender, and the course of the maxillary artery. CONCLUSION: Our study emphasizes the marked inter- and intra-individual variability of the maxillary and middle meningeal arterial courses. We confirmed the proximity of the arteries to the condylar process. Extensive surgical experience and thorough preparation for each individual case are essential to prevent iatrogenic vascular injury.

ASA score and procedure type predict complications and costs in maxillofacial reconstructive surgery: a retrospective study using a hospital administrative database.

BACKGROUND: Reconstruction of osseous and soft tissue defects after surgical resection of oral cavity cancers can be achieved by a single-stage procedure with a microvascular bone flap or by a two-step approach with a soft tissue flap and subsequent bone augmentation. The therapeutic approach should be selected based on the patient’s needs. Economic pressure requires preoperative risk assessment and estimation of the postoperative course. Flat-rate reimbursement systems via diagnosis-related groups with insufficient morbidity adjustments and financial sanction of medical complications might additionally cause false incentives in the choice of treatment. OBJECTIVE: This study aimed to assess the influence of the type of flap chosen for maxillofacial reconstructive surgery on the total costs. Complication rates of different types of flap surgery and their prediction by a preoperative risk assessment tool (American Society of Anesthesiologists [ASA] score) were determined. Overall, the fairness of the current reimbursement system was rated. METHODS: Patient characteristics, clinical data, and data on total costs and reimbursement of patients aged 18 years and older having undergone maxillofacial reconstructive flap surgery at the University Hospital of Zurich (Switzerland) between 2012 and 2014 were analysed. The preoperative risk was classified by the ASA score. Complications were graded according to the Clavien-Dindo classification system and the comprehensive complication index (CCI). Statistical analysis included Spearman and Pearson rank correlation, Kruskal-Wallis and Mann-Whitney nonparametric tests, and linear regression analysis. RESULTS: 129 patients were included in this study. Soft tissue flaps were performed in 82 patients, of which 56 were radial forearm flaps (43.4%), bone flaps in 41 patients, of which 32 were fibula flaps (24.8%), and combined flaps in 6 patients (4.7%). Patients with fibula flaps showed a significantly higher CCI and higher total costs. Higher preoperative ASA scores were significantly associated with increased length of stay, total costs and complications. Both the ASA score and reconstruction with a radial forearm flap were significant predictors of complications and total costs. Total median costs for radial forearm flaps were CHF 50,560 (reimbursement: CHF 60,851; difference: CHF 10,291) and for fibula flaps CHF 66,982 (reimbursement: CHF 58,218; difference: CHF −8,764). CONCLUSION: The ASA score allows a reliable preoperative assessment of patient outcomes and financial burden in maxillofacial reconstructive flap surgery. The type of flap reconstruction significantly influences complications and ultimately total costs. The current reimbursement system via diagnosis-related groups (DRGs) does not take sufficient account of this fact. Adaptations are therefore needed to prevent misplaced incentives to the detriment of patients.

SalvGlandDx - a comprehensive salivary gland neoplasm specific next generation sequencing panel to facilitate diagnosis and identify therapeutic targets.

Diagnosis of salivary gland neoplasms is often challenging due to their high morphological diversity and overlaps. Several recurrent molecular alterations have been described recently, which can serve as powerful diagnostic tools and potential therapeutic targets (e.g. NTRK or RET fusions). However, current sequential molecular testing can be expensive and time consuming. In order to facilitate the diagnosis of salivary gland neoplasms, we designed an all-in-one RNA-based next generation sequencing panel suitable for the detection of mutations, fusions and gene expression levels (including NR4A3) of 27 genes involved in salivary gland neoplasms. Here we present the validation of the "SalvGlandDx" panel on FFPE histological specimen including fine needle aspiration (FNA) cell block material, against the standard methods currently used at our institution. In a second part we describe selected unique cases in which the SalvGlandDx panel allowed proper diagnosis and new insights into special molecular characteristics of selected salivary gland tumors. We characterize a unique salivary gland adenocarcinoma harboring a ZCCHC7-NTRK2 fusion, a highly uncommon spindle cell and pseudoangiomatoid adenoid-cystic carcinoma with MYBL1-NFIB fusion, and a purely oncocytic mucoepidermoid carcinoma, whereas diagnosis could be made by detection of a CRTC3-MAML2 rearrangement on the cell block specimen of the FNA. Further, a rare case of a SS18-ZBTB7A rearranged low-grade adenocarcinoma previously described as potential spectrum of microsecretory adenocarcinoma, is reported. In addition, features of six cases within the spectrum of polymorphous adenocarcinoma / cribriform adenocarcinoma of salivary gland including PRKD1 p.E710D mutations and novel fusions involving PRKAR2A-PRKD1, SNX9-PRKD1 and ATL2-PRKD3, are described.

Cell seeding accelerates the vascularization of tissue engineering constructs in hypertensive mice.

Rapid blood vessel ingrowth into transplanted constructs represents the key requirement for successful tissue engineering. Seeding three-dimensional scaffolds with suitable cells is an approved technique for this challenge. Since a plethora of patients suffer from widespread diseases that limit the capacity of neoangiogenesis (e.g., hypertension), we investigated the incorporation of cell-seeded poly-L-lactide-co-glycolide scaffolds in hypertensive (BPH/2J, group A) and nonhypertensive (BPN/3J, group B) mice. Collagen-coated scaffolds (A1 and B1) were additionally seeded with osteoblast-like (A2 and B2) and mesenchymal stem cells (A3 and B3). After implantation into dorsal skinfold chambers, inflammation and newly formed microvessels were measured using repetitive intravital fluorescence microscopy for 2 weeks. Apart from a weak inflammatory response in all groups, significantly increased microvascular densities were found in cell-seeded scaffolds (day 14, A2: 192 ± 12 cm/cm2, A3: 194 ± 10 cm/cm2, B2: 249 ± 19 cm/cm2, B3: 264 ± 17 cm/cm2) when compared with controls (A1: 129 ± 10 cm/cm2, B1: 185 ± 8 cm/cm2). In this context, hypertensive mice showed reduced neoangiogenesis in comparison with nonhypertensive animals. Therefore, seeding approved scaffolds with organ-specific or pluripotent cells is a very promising technique for tissue engineering in hypertensive organisms.

Correction: Stalder, et al.; Value of SUVmax for the Prediction of Bone Invasion in Oral Squamous Cell Carcinoma. Biology 2020, 9, 23.

The authors would like to make a correction to their published paper [1][...].

Radiologic Analysis of Surgically Treated Fractures of the Condylar Process by an Endoscopic-Assisted Transoral Approach.

PURPOSE: This study analyzed the radiologic outcomes of patients with unilateral mandibular condylar fractures treated with open reduction-internal fixation (ORIF) through a transoral approach. PATIENTS AND METHODS: In this retrospective study, the radiologic images of 40 patients who underwent open reduction-internal fixation through a transoral approach were presented to 2 independent examiners. All patients underwent the surgical procedure between January 2015 and December 2016 at the Department of Cranio-Maxillofacial Surgery at UniversitätsSpital Zürich and were included in a previous functional outcome study. The surgical results were analyzed and graded as poor, acceptable, or good. The examiners declared whether they would have made any intraoperative revisions if the radiologic information had been available. Finally, the examiners estimated the required duration of elastic intermaxillary fixation (IMF) from the radiologic images, which was compared with the actual duration. RESULTS: Fracture reduction was classified as good in 33 cases (82.5%), acceptable in 5 cases, and poor in 2 cases by one examiner and as good in 32 cases (80%), acceptable in 6 cases, and poor in 2 cases by the other examiner. The inter-rater reliability was determined to be good (Cohen κ = 0.92). Correct osteosynthesis placement was found in 19 cases by one examiner and in 21 cases by the other examiner, with good inter-rater reliability (κ = 0.8). Moderate inter-rater reliability (κ = 0.4) was found for the required duration of elastic IMF. Furthermore, the estimated elastic IMF duration matched the actual duration in fewer than half of the cases. CONCLUSIONS: It is feasible to achieve reliably good radiologic results when operating on condylar process fractures by a transoral approach with endoscopic assistance and angled instruments. Intraoperative 3-dimensional imaging enables instant quality control and prompts surgical revision if needed.

Value of SUVmax for the Prediction of Bone Invasion in Oral Squamous Cell Carcinoma.

In advanced oral squamous cell carcinoma (OSCC), accurate planning of surgical resection and reconstruction are crucial for outcome and postoperative function. For OSCC close to the maxilla or mandible, prediction of bone invasion is necessary. The aim of this study was to examine whether metabolic tumor imaging obtained by fluorodeoxyglucose positron emission tomography (FDG-PET) could enhance preoperative predictability of bone invasion. We performed an analysis of 84 treatment-naïve OSCCs arising from gum (upper and lower), hard palate, floor of mouth, and retromolar trigone treated at the University Hospital Zurich, Switzerland, who underwent wide local excision with free flap reconstruction between 04/2010 and 09/2018 and with available preoperative FDG-PET. Prediction of bone invasion by metabolic tumor imaging such as maximum standardized uptake value (SUVmax) was examined. On definitive histopathology, bone invasion was present in 47 of 84 cases (56%). The probability of bone infiltration increased with a higher pretherapeutic SUVmax in an almost linear manner. A pretherapeutic SUVmax of primary tumor below 9.5 ruled out bone invasion preoperatively with a high specificity (97.6%). The risk of bone invasion was 53.6% and 71.4% for patients with SUVmax between 9.5-14.5 and above 14.5, respectively. Patients with bone invasion had worse distant metastasis-free survival compared to patients without bone invasion (log-rank test, p = 0.032). In conclusion, metabolic tumor imaging using FDG-PET could be used to rule out bone invasion in oral cancer patients and may serve in treatment planning.

Precision of Simultaneous Guided Dental Implantation in Microvascular Fibular Flap Reconstructions With and Without Additional Guiding Splints.

PURPOSE: Dental rehabilitation in patients receiving free flap reconstructive surgery on the mandible or maxilla is an important part of bringing patients back to normality in both a physical and psychological way. It is therefore important to be able to do this in the fastest way possible. Virtual preplanned reconstructions of jaws with implants placed simultaneously are a good way to expedite this process and have the advantage of allowing true backward planning to achieve bone placement where it prosthetically needs to be. Thus, the precise transfer of the virtually preplanned implant position to the intraoperative situation is crucial for prosthetic rehabilitation. PATIENTS AND METHODS: We compared a control group of patients (4 patients with 15 implants) with preplanned fibular reconstructions of the mandible with implants incorporated in the planning and a trial group of patients (4 patients with 13 implants) with an additional intraoperative splint for the verification of the implants' angulation. The preoperative planning and postoperative computed tomography scans were compared. RESULTS: The average positioning error at bone level was 0.9 mm in the trial group and 1.3 mm in the control group. The average angulation error in the buccolingual plane was 2.9° in the trial group and 5.5° in the control group; axially, the difference was 6.3° in the trial group and 4.1° in the control group. CONCLUSIONS: The use of digitally backward-planned fibula cutting guides with direct dental implant positioning is feasible, and the precision found is comparable with that of standard splint-guided implant placement in the general population. Although the axial angulation error has more to do with anatomic variance and positioning of the bony cutting guide, the trial population clearly profited from the additional splint in the important buccolingual angulation. Overall, we showed a high level of precision over all implants in both groups.

Retrospective analysis of 471 surgically treated zygomaticomaxillary complex fractures.

PURPOSE: Zygomaticomaxillary complex (ZMC) fractures are frequent in facial trauma; only fractures of the mandible are more common. Although the frequency of these fractures is geographically consistent, the aetiology differs widely among countries and even regions. Differences in socio-economic status and the ageing population seem to be two causes. This retrospective epidemiological study evaluates patients who were surgically treated for ZMC fractures at a Swiss university clinic. MATERIALS AND METHODS: This study included 471 patients who were surgically treated for ZMC fractures in an oral and maxillofacial surgery clinic at a Swiss university hospital between January 2004 and December 2012. Complicated fractures such as LeFort II/III and bilateral ZMC fractures were excluded. Data on gender, age, and type of trauma were recorded. Fractures were classified by aetiology: motorised road traffic (car or motorcycle), bicycle, interpersonal violence, sports, falls (both less than and greater than 3 m in height) and other causes. RESULTS: A total of 350 patients were male (74%), and 121 were female (26%). The ZMC fractures were most likely to occur in the third decade (117 cases, 25%). A predominance of male patients was found in the young age groups, but an equal ratio was found in the elderly groups. Etiologically, falls of less than 3 m were the most common cause of ZMC fractures (125 cases, 27%). Interpersonal violence was second (88 patients, 19%); male patients dominated this group, which had a male-to-female ratio of 21:1. A predominance of male patients was found in every subdivision when analysing by aetiology and gender. The lowest proportion of males (57%) was found for falls of less than 3 m. CONCLUSION: In our study, interpersonal violence and falls outnumbered road traffic accidents among causes of maxillofacial fractures. This is probably a consequence of strict road and work laws. Additionally, the older and more active populations accounted for the highest proportion of falls, and young male patients were the predominant victims of ZMC fractures.

Incidence and frequency of nondental incidental findings on cone-beam computed tomography.

PURPOSE: The purpose of the present study was to determine the frequency of relevant nondental related incidental findings in cone-beam computed tomography (CBCT) of the head and neck. MATERIAL AND METHODS: Nine hundred ninety-nine images were retrospectively reviewed for incidental findings. Those were defined as carotid artery calcification (CAC), paranasal sinus findings (PSF), sialolithiasis of the parotid gland (SP) or submandibular gland (SSub), calcification of the ligamentum stylohyoideum (CLS), and Stafne bone cavity (SBC). All datasets obtained between 2010 and 2014 at a university-based school of dental medicine in Switzerland were reviewed. Demographic data such as age and sex were also recorded. RESULTS: A total of 350 incidental findings within the 999 CBCT scans were identified. The most frequent finding was PSF (27.8%), followed by CLS (11.6%), CAC (5.3%), and SSub (0.8%). No SP or SBC was found. Incidental findings were most frequent between 61 and 70 years of age. Males had a higher prevalence in CAC, PSF, and SSub than females. CONCLUSIONS: These results underscore the need for a complete examination of every CBCT image beyond the region of interest.

The Effects of Preoperative Radiotherapy on Head and Neck Free Flap Anastomosis Success.

PURPOSE: The long-term survival benefit of neoadjuvant radiotherapy for oropharyngeal tumors is controversially discussed in the literature. To bring more light into this important debate, we evaluated our cases. PATIENTS AND METHODS: In this retrospective study the main focus was the relationship between neoadjuvant irradiation and anastomosis failure. Other influencing factors including previous operative treatment and tumor stage and type also were studied. RESULTS: In total, 7 anastomoses failed (total failure rate, 8.4%; n = 83); 1 of the 7 underwent neoadjuvant irradiation (failure rate, 3.1%; n = 32). All 7 anastomosis failures were in squamous cell carcinoma cases, with 5 of them staged as T4. CONCLUSION: Our data suggest that neoadjuvant radiotherapy for oropharyngeal carcinoma does not increase the risk of postoperative anastomosis failure compared with surgical reconstruction alone. Furthermore, the data suggest a correlation between the stage and type of tumor.

Scapular Free Vascularised Bone Flaps for Mandibular Reconstruction: Are Dental Implants Possible?

OBJECTIVES: Free fibula flap remains the flap of choice for reconstruction of mandibular defects. If free fibula flap is not possible, the subscapular system of flaps is a valid option. In this study, we evaluated the possibility of dental implant placement in patients receiving a scapular free flap for oromandibular reconstruction. MATERIAL AND METHODS: We retrospectively reviewed 10 patients undergoing mandible reconstruction with a subscapular system free-tissue (lateral border of the scapula) transfer at the University Hospital Zürich between January 1, 2010 and January 1, 2013. Bone density in cortical and cancellous bone was measured in Hounsfield units (HU). Changes of bone density, height and width were analysed using IBM SPSS Statistics 22. Comparisons of bone dimensions as well as bone density were performed using a chi-square test. RESULTS: Ten patients were included. Implantation was conducted in 50%. However, all patients could have received dental implants considering bone stock. Loss of bone height and width were significant (P < 0.001). There was a statistical significant increase in bone density in cortical (P < 0.001) and cancellous (P = 0.004) bone. CONCLUSIONS: Dental implants are possible after scapular free flap reconstruction of oromandibular defects. Bone height and width were reduced, while bone density increased with time.

The 3dMD photogrammetric photo system in cranio-maxillofacial surgery: Validation of interexaminer variations and perceptions.

BACKGROUND: Three-dimensional photography of the face is increasingly used to overcome the downsides of conventional photography or anthropometry regarding reliable evaluation. However, the precision of such a system has to be validated before it can be implemented for clinical use. MATERIAL AND METHODS: Eight people were photographed with the 3dMDface system using lighting from sets of 2 × 4 compact fluorescent lights in a clinical photography room without natural light sources. Two different operators then individually, and without interaction, marked 27 different anatomical landmarks using the 3dMD Patient software. During this process, the operators were fully blinded against each other. The purpose of the study was to determine the repeatability and accuracy of the system when used by different operators and at different times. The 3D differentiation was analyzed using mixed ANOVA with person as the random factor, and operator, repetition, and landmark as the fixed factors. The ANOVA was followed by a Ryan-Einot-Gabriel-Welsch F post-hoc test for landmarks. RESULTS: Statistical analysis grouped the landmarks into three subgroups: high precision, medium precision and low precision. CONCLUSIONS: Virtual 3D models derived from the 3dMDface system not only provide a high level of technical precision but also of intra- and interobserver reliability regarding landmark identification. However, some of the classical landmarks are not reliable when it comes to virtual models; these are generally landmarks that examiners of real patients would tend to identify using palpation of underlying bony structures, such as the soft gonion.

Closed versus open treatment of mandibular condylar process fractures: A meta-analysis of retrospective and prospective studies.

INTRODUCTION: The treatment of fractures of the mandibular process remains controversial, although there is a trend towards open reduction and internal fixation. This study compared open and closed treatments and assessed the results with a meta-analysis. MATERIALS AND METHODS: A literature search of PubMed found eight studies that met the search criteria and were included in the meta-analysis. RESULTS: The studies increasingly suggest better results for open treatment, in terms of mouth opening, protrusion, laterotrusion, pain, and malocclusion. In the meta-analysis, the outcome was significantly better for laterotrusion and protrusion in patients treated by open reduction and internal fixation. CONCLUSION: Due to the different study protocols and lack of information on classification, follow-up time, and inclusion criteria, comparison of the studies remains difficult and further prospective, randomized studies should examine these issues.

Decelerated vascularization in tissue-engineered constructs in association with diabetes mellitus in vivo.

AIMS: Rapid blood vessel ingrowth in transplanted tissue engineering constructs is the key factor for successful incorporation, but many potential patients who may use engineered tissues suffer from widespread diseases that limit the capacity of neovascularization (e.g. diabetes). Thus, in vivo vascularization analyses of tissue-engineered constructs in angiogenically affected organisms are required. METHODS: We therefore investigated the in vivo incorporation of collagen-coated and cell-seeded poly-L-lactide-co-glycolide scaffolds in diabetic B6.BKS(D)-Lepr(db)/J mice using repetitive intravital fluorescence microscopy over a time period of two weeks. For this purpose, scaffolds were seeded with osteoblast-like or bone marrow mesenchymal stem cells and implanted into the dorsal skinfold chambers of diabetic and non-diabetic (C57BL/6) mice. RESULTS: Apart from slightly increased inflammatory parameters, diabetic mice showed significantly reduced capillary densities compared with non-diabetic animals from day 6 onward. In line with previous studies, more densely meshed microvascular networks were demonstrated in cell-seeded than in collagen-coated scaffolds from day 6 onward within the single groups (diabetic and control). CONCLUSIONS: A large number of patients who suffer from systemic diseases that affect angiogenesis would profit from tissue engineering. Therefore, the challenge for the clinical introduction of tissue-engineered constructs will be to overcome the decreased angiogenesis in diabetic organisms.