Potential of poly(alkylene terephthalate)s to control endothelial cell adhesion and viability.

Poly(ethylene terephthalate) (PET) is known for its various useful characteristics, including its applicability in cardiovascular applications, more precisely as synthetic bypass grafts for large diameter (≥ 6 mm) blood vessels. Although it is widely used, PET is not an optimal material as it is not interactive with endothelial cells, which is required for bypasses to form a complete endothelium. Therefore, in this study, poly(alkylene terephthalate)s (PATs) have been studied. They were synthesized via a single-step solution polycondensation reaction, which requires mild reaction conditions and avoids the use of a catalyst or additives like heat stabilizers. A homologous series was realized in which the alkyl chain length varied from 5 to 12 methylene groups (n = 5-12). Molar masses up to 28,000 g/mol were obtained, while various odd-even trends were observed with modulated differential scanning calorimetry (mDSC) and rapid heat-cool calorimetry (RHC) to access the thermal properties within the homologous series. The synthesized PATs have been subjected to in vitro cell viability assays using Human Umbilical Vein Endothelial Cells (HUVECs) and Human Dermal Microvascular Endothelial Cells (HDMECs). The results showed that HUVECs adhere and proliferate most pronounced onto PAT(n=9) surfaces, which could be attributed to the surface roughness and morphology as determined by atomic force microscopy (AFM) (i.e. Rq = 204.7 nm). HDMECs were investigated in the context of small diameter vessels and showed superior adhesion and proliferation after seeding onto PAT(n=6) substrates. These preliminary results already pave the way towards the use of PAT materials as substrates to support endothelial cell adhesion and growth. Indeed, as superior endothelial cell interactivity compared to PET was observed, time-consuming and costly surface modifications of PET grafts could be avoided by exploiting this novel material class.

Impact of opioid-free anesthesia on complications after deep inferior epigastric perforator flap surgery: A retrospective cohort study.

This study measured the number of complications after deep inferior epigastric perforator (DIEP) flap reconstruction performed under opioid-free anesthesia (OFA) combined with goal-directed fluid therapy or opioid anesthesia with liberal fluid therapy (OA). This retrospective cohort study consisted of 204 patients who underwent DIEP flap reconstruction at AZSint Jan Brugge between April 2014 and March 2019. Primary outcomes were complications, according to the Clavien-Dindo classification and the length of hospital stay (LOS). The secondary outcomes were flap failure, postoperative nausea and vomiting (PONV), postoperative pain, postoperative opioid consumption, and postoperative skin flap temperature. OFA included a combination of dexmedetomidine, lidocaine, and ketamine without any opioid administered pre- or intraoperatively. OA included a combination of sufentanil and remifentanil. OFA patients received strict goal-directed fluid therapy, whereas OA patients received liberal fluids to maintain perfusion pressure. All patients except 7 (TIVA with remifentanil) received inhalation anesthesia combined with an infusion of propofol. Of the 204 patients, 55 received OFA and 149 received OA. There were no differences in major complications, but fewer minor complications in the OFA group (17.9% vs. 51.4% and P < 0.001). Flap failure occurred in three patients of the OA group. Six patients developed flap thrombosis (five OA patients and one OFA patient). OFA was associated with fewer postoperative opioids, shorter LOS, less PONV, and less pain. In patients without previous nausea, the PONV incidence was higher in the OA group than in the OFA group (12.7% vs. 43.6% and P < 0.001). Patients with previous nausea more frequently required postoperative opioids and had a nausea rate of 60.87%.

High-throughput fabrication of vascularized adipose microtissues for 3D bioprinting.

For patients with soft tissue defects, repair with autologous in vitro engineered adipose tissue could be a promising alternative to current surgical therapies. A volume-persistent engineered adipose tissue construct under in vivo conditions can only be achieved by early vascularization after transplantation. The combination of 3D bioprinting technology with self-assembling microvascularized units as building blocks can potentially answer the need for a microvascular network. In the present study, co-culture spheroids combining adipose-derived stem cells (ASC) and human umbilical vein endothelial cells (HUVEC) were created with an ideal geometry for bioprinting. When applying the favourable seeding technique and condition, compact viable spheroids were obtained, demonstrating high adipogenic differentiation and capillary-like network formation after 7 and 14 days of culture, as shown by live/dead analysis, immunohistochemistry and RT-qPCR. Moreover, we were able to successfully 3D bioprint the encapsulated spheroids, resulting in compact viable spheroids presenting capillary-like structures, lipid droplets and spheroid outgrowth after 14 days of culture. This is the first study that generates viable high-throughput (pre-)vascularized adipose microtissues as building blocks for bioprinting applications using a novel ASC/HUVEC co-culture spheroid model, which enables both adipogenic differentiation while simultaneously supporting the formation of prevascular-like structures within engineered tissues in vitro.

Bilateral DIEP Flap Breast Reconstruction to a Single Set of Internal Mammary Vessels: Technique, Safety, and Outcomes after 250 Flaps.

BACKGROUND: The deep inferior epigastric artery perforator (DIEP) flap is considered the gold standard in autologous breast reconstruction. In bilateral cases, both flaps are often anastomosed to the internal mammary vessels on either side of the sternum. The authors propose a method in which both flaps are anastomosed to only the right side internal mammary artery and vein. METHODS: Between November of 2009 and March of 2018, 125 patients underwent bilateral DIEP flap breast reconstruction with this technique. One flap is perfused by the anterograde proximal internal mammary artery and the second one by the retrograde distal internal mammary artery after presternal tunneling. Patient demographics and operative details were reviewed retrospectively. RESULTS: Two hundred fifty flaps were performed. One hundred fifty-two flaps were prophylactic or primary reconstructions (60.8 percent), 70 were secondary reconstructions (28 percent), and 28 were tertiary reconstructions (11.2 percent). Mean patient age was 46 years, and the mean body mass index was 25 kg/m. Sixty patients underwent radiation therapy or chemotherapy (48 percent). The authors encountered one significant partial failure (0.4 percent) and nine complete flap failures (3.6 percent). The authors did not see a statistically significant predisposition for failure comparing the retrograde with the anterograde flow flaps, nor when comparing the tunneled with the nontunneled flaps. CONCLUSIONS: The authors' results show that anastomosing both DIEP flaps to a single set of mammary vessels is safe and reliable. The authors conclude that the retrograde flow through the distal internal mammary artery is sufficient for free flap perfusion and that subcutaneous tunneling of a free flap pedicle does not predispose to flap failure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Vascular adhesion protein-1: Role in human pathology and application as a biomarker.

Vascular adhesion protein-1 (VAP-1) is a member of the copper-containing amine oxidase/semicarbazide-sensitive amine oxidase (AOC/SSAO) enzyme family. SSAO enzymes catalyze oxidative deamination of primary amines, which results in the production of the corresponding aldehyde, hydrogen peroxide and ammonium. VAP-1 is continuously expressed as a transmembrane glycoprotein in the vascular wall during development and facilitates the accumulation of inflammatory cells into the inflamed environment in concert with other leukocyte adhesion molecules. The soluble form of VAP-1 is released into the circulation mainly from vascular endothelial cells. Over- and under-expression of sVAP-1 result in alterations of the reported reaction product levels, which are involved in the pathogenesis of multiple human diseases. The combination of enzymatic and adhesion capacities as well as its strong association with inflammatory pathologies makes VAP-1 an interesting therapeutic target for drug discovery. In this article, we will review the general characteristics and biological functions of VAP-1, focusing on its important role as a prognostic biomarker in human pathologies. In addition, the potential therapeutic application of VAP-1 inhibitors will be discussed.