Currently, systemic immunosuppression is used in vascularized composite allotransplantation (VCA). This treatment has considerable side effects and reduces the quality of life of VCA recipients. We loaded the immunosuppressive drug tacrolimus into a self-assembled hydrogel, which releases the drug in response to proteolytic enzymes that are overexpressed during inflammation. A one-time local injection of the tacrolimus-laden hydrogel significantly prolonged graft survival in a Brown Norway-to-Lewis rat hindlimb transplantation model, leading to a median graft survival of >100 days compared to 33.5 days in tacrolimus only-treated recipients. Control groups with no treatment or hydrogel only showed a graft survival of 11 days. Histopathological evaluation, including anti-graft antibodies and complement C3, revealed significantly reduced immune responses in the tacrolimus-hydrogel group compared with tacrolimus only. In conclusion, a single-dose local injection of an enzyme-responsive tacrolimus-hydrogel is capable of preventing VCA rejection for >100 days in a rat model and may offer a new approach for immunosuppression in VCA.

Our findings demonstrate that localized immunosuppression with TAC hydrogel is a long-term safe and reliable treatment. It may reduce the burden of systemic immunosuppression in vascularized composite allotransplantation, potentially boosting the clinical application of this surgical intervention.

Background: Even though the benefit of free tissue transfer is uncontested in complex reconstructive cases, vascular compromise and/or flap failure remain a challenge for the surgeon and identification of possible risk factors can aid in the preoperative planning. The aim of this study was to identify the individual risk factors leading to flap failure and/or vascular compromise in free tissue transfers in a single institution over a period of 10 years and to create an index predicting these problems, as well as finding predictors of other postoperative complications. Methods: Data from all the patients undergoing free tissue transfers between 2009 and 2018 were retrospectively analyzed (demographics, comorbidities, flap failure, vascular compromise, and other complications). The results from the univariate and multivariate analyses were used to create an index. Results: A predictability index with three classes (low, moderate, and high risk) was calculated for each patient, based on defect etiology and the presence of coronary heart disease, diabetes, smoking, peripheral arterial vascular disease, and arterial hypertension. A patient with moderate-risk index had 9.3 times higher chances of developing vascular compromise than those in the low-risk group, while a high-risk index had 18.6 higher odds ( p = 0.001). American Society of Anesthesiologists (ASA) classification was found to be a predictor of complications in free tissue transfer ( p = 0.001).

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BackgroundProducing a rich, personalized Web-based consultation tool for plastic surgeons and patients is challenging.Objective(1) To develop a computer tool that allows individual reconstruction and simulation of 3-dimensional (3D) soft tissue from ordinary digital photos of breasts, (2) to implement a Web-based, worldwide-accessible preoperative surgical planning platform for plastic surgeons, and (3) to validate this tool through a quality control analysis by comparing 3D laser scans of the patients with the 3D reconstructions with this tool from original 2-dimensional (2D) pictures of the same patients.MethodsThe proposed system uses well-established 2D digital photos for reconstruction into a 3D torso, which is then available to the user for interactive planning. The simulation is performed on dedicated servers, accessible via Internet. It allows the surgeon, together with the patient, to previsualize the impact of the proposed breast augmentation directly during the consultation before a surgery is decided upon. We retrospectively conduced a quality control assessment of available anonymized pre- and postoperative 2D digital photographs of patients undergoing breast augmentation procedures. The method presented above was used to reconstruct 3D pictures from 2D digital pictures. We used a laser scanner capable of generating a highly accurate surface model of the patient’s anatomy to acquire ground truth data. The quality of the computed 3D reconstructions was compared with the ground truth data used to perform both qualitative and quantitative evaluations.ResultsWe evaluated the system on 11 clinical cases for surface reconstructions and 4 clinical cases of postoperative simulations, using laser surface scan technologies showing a mean reconstruction error between 2 and 4 mm and a maximum outlier error of 16 mm. Qualitative and quantitative analyses from plastic surgeons demonstrate the potential of these new emerging technologies.ConclusionsWe tested our tool for 3D, Web-based, patient-specific consultation in the clinical scenario of breast augmentation. This example shows that the current state of development allows for creation of responsive and effective Web-based, 3D medical tools, even with highly complex and time-consuming computation, by off-loading them to a dedicated high-performance data center. The efficient combination of advanced technologies, based on analysis and understanding of human anatomy and physiology, will allow the development of further Web-based reconstruction and predictive interfaces at different scales of the human body. The consultation tool presented herein exemplifies the potential of combining advancements in the core areas of computer science and biomedical engineering with the evolving areas of Web technologies. We are confident that future developments based on a multidisciplinary approach will further pave the way toward personalized Web-enabled medicine.

Dimethyloxalylglycine treatment significantly increases VEGF and HIF-1α expression in endothelial cell cultures and enhances skin flap survival in vivo in a rat model.

Metal oxide nanoparticles have emerged as exceptionally potent biomedical sensors and actuators due to their unique physicochemical features. Despite fascinating achievements, the current limited understanding of the molecular interplay between nanoparticles and the surrounding tissue remains a major obstacle in the rationalized development of nanomedicines, which is reflected in their poor clinical approval rate. This work reports on the nanoscopic characterization of inorganic nanoparticles in tissue by the example of complex metal oxide nanoparticle hybrids consisting of crystalline cerium oxide and the biodegradable ceramic bioglass. A validated analytical method based on semiquantitative X‐ray fluorescence and inductively coupled plasma spectrometry is used to assess nanoparticle biodistribution following intravenous and topical application. Then, a correlative multiscale analytical cascade based on a combination of microscopy and spectroscopy techniques shows that the topically applied hybrid nanoparticles remain at the initial site and are preferentially taken up into macrophages, form apatite on their surface, and lead to increased accumulation of lipids in their surroundings. Taken together, this work displays how modern analytical techniques can be harnessed to gain unprecedented insights into the biodistribution and biotransformation of complex inorganic nanoparticles. Such nanoscopic characterization is imperative for the rationalized engineering of safe and efficacious nanoparticle‐based systems.