Poly-ε-Caprolactone/Fibrin-Alginate Scaffold: A New Pro-Angiogenic Composite Biomaterial for the Treatment of Bone Defects

We hypothesized that a composite of 3D porous melt-electrowritten poly-ɛ-caprolactone (PCL) coated throughout with a porous and slowly biodegradable fibrin/alginate (FA) matrix would accelerate bone repair due to its angiogenic potential. Scanning electron microscopy showed that the open pore structure of the FA matrix was maintained in the PCL/FA composites. Fourier transform infrared spectroscopy and differential scanning calorimetry showed complete coverage of the PCL fibres by FA, and the PCL/FA crystallinity was decreased compared with PCL. In vitro cell work with osteoprogenitor cells showed that they preferentially bound to the FA component and proliferated on all scaffolds over 28 days. A chorioallantoic membrane assay showed more blood vessel infiltration into FA and PCL/FA compared with PCL, and a significantly higher number of bifurcation points for PCL/FA compared with both FA and PCL. Implantation into a rat cranial defect model followed by microcomputed tomography, histology, and immunohistochemistry after 4- and 12-weeks post operation showed fast early bone formation at week 4, with significantly higher bone formation for FA and PCL/FA compared with PCL. However, this phenomenon was not extrapolated to week 12. Therefore, for long-term bone regeneration, tuning of FA degradation to ensure syncing with new bone formation is likely necessary.

Regulation of lymphangiogenesis by extracellular vesicles in cancer metastasis

Metastasis is not only one of the hallmarks of cancer but, unfortunately, it also is the most accurate biomarker for poor prognosis. Cancer cells metastasize through two different but eventually merged routes, the vasculature and lymphatic systems. The processes of cancer metastasis through blood vessel have been extensively studied and are well documented in the literature. In contrast, metastasis through the lymphatic system is less studied. Most people believe that cancer cells metastasize through lymphatic vessel are passive because the lymphatic system is thought to be a sewage draining system that collects whatever appears in the tissue fluid. It was recently found that cancer cells disseminated from lymphatic vessels are protected from being destroyed by our body’s defense system. Furthermore, some cancer cells or cancer-associated immune cells secrete lymphangiogenic factors to recruit lymphatic vessel infiltration to the tumor region, a process known as lymphangiogenesis. To ensure the efficiency of lymphangiogenesis, the lymphangiogenic mediators are carried or packed by nanometer-sized particles named extracellular vesicles. Extracellular vesicles are lipid bilayer particles released from eventually every single cell, including bacterium, with diameters ranging from 30 nm (exosome) to several micrometers (apoptotic body). Components carried by extracellular vesicles include but are not limited to DNA, RNA, protein, fatty acid, and other metabolites. Recent studies suggest that cancer cells not only secrete more extracellular vesicles but also upload critical mediators required for lymphatic metastasis onto extracellular vesicles. This review will summarize recent advances in cancer lymphatic metastasis and how cancer cells regulate this process via extracellular vesicle-dependent lymphangiogenesis.

Abstract P684: Treatment of Hypercoagulability-Induced New Neurovascular Events Using Enoxaparin vs DOACs (THINNED): A Retrospective Study

Introduction: The incidence of stroke is higher in patients with malignancy, especially within a few months of diagnosis and in more aggressive cancers. This phenomenon may be explained by an inherent hypercoagulable state, tumor embolism, vessel infiltration, or as a side effect from cancer treatment. Notably, stroke in cancer patients is associated with poor functional outcomes and reduced survival. Currently, however, there are no clear guidelines for antithrombotic management for prevention of recurrent strokes in these patients. Methods: We conducted a single-center retrospective chart review from 2013-2019. All adult patients with an ischemic stroke occurring with active malignancy and who then received either a direct oral anticoagulant (DOAC) or low molecular weight heparin (LMWH) were included. Patients with hemorrhagic stroke, an intracranial malignancy, or who were immediately admitted to hospice were excluded. Results: A total of 55 patients were included with a mean age of 71.8 years (range 28-96), 60% females, 87.3% first-time strokes, and 54.9% with metastatic disease. After stroke, 25 patients received a DOAC and 30 received LMWH for anticoagulation with a mean follow-up of 403 days. Between these two groups, most presentation and treatment characteristics were similar except for baseline hypertension, hyperlipidemia, additional initiation of an antiplatelet, and follow-up time. There was no difference in either stroke recurrence (DOAC vs LMWH: OR 2.61 [0.51-13.45], p=0.252) or time to recurrent stroke (DOAC vs LMWH: HR 1.68, p=0.446), but both analyses required adjustment for additional initiation of an antiplatelet—which was significantly protective regardless of anticoagulation choice (p=0.021* and p=0.017*, respectively). There was a trend towards improved survival if placed on a DOAC (HR 0.27, p=0.051), even after adjusting for metastatic disease. Conclusions: In this initial study of cancer patients with ischemic stroke, anticoagulation choice made no difference on stroke recurrence; however, addition of an antiplatelet agent was significantly protective. There was also a trend towards improved survival on a DOAC. Additional prospective data incorporating a larger sample size could further validate these findings.

The characteristics of c-MET and HER2 expression in gastric carcinoma and its correlation with clinical-pathological parameters.

e15566 Background: The aim of this study was to determine whether overexpression of c-MET or HER2 had an effect on the clinical-pathological parameters and / or the prognosis of gastric carcinoma, as well as a direct correlation among those parameters. Methods: 134 gastric resectates were archived between 2007-2012 and retrospectively examined for c-MET and HER2 expression via immunohistochemistry (IHC). The HER2 status IHC2 + was additionally verified by means of Chromogenic in situ hybridization (CISH). Statistical data analysis was performed on the basis of the parameters acquired in the prospective multicentre observation study QCGC'07 / 09. Results: A total of 71 patients (53%) were found to express c-MET low and 63 patients (47%) expressed c-MET high, 122 patients (91%) were found to be HER2 negative and 12 persons (9%) were HER2 positive. C-MET high was significantly more pronounced in the Lauren intestinal type (63.8%, p = 0.001) and moderately to poorly differentiated tumour tissue (G2 50.9%, G3 43.9%, p = 0.038) as well es tissue with lymph vessel infiltration (L1 59.1%, p = 0.039). HER2 showed no significant effect on the clinical-pathological parameters. The median overall survival was shown to be shortened for the c-MET high-expressing (c-MET low 56 months, SD: ± 24.67; 95% CI: 7.65-104.36 vs. c-MET high 32 months, SD: ± (median-OS HER2 negative 38 months, SD: ± 14.11, 95% CI: 10.35-65, p = 0.839), and HER2 negative, 65, median-OS HER2 positive not reached, p = 0.305) patients. 8/134 resectates (5.97%, p = 0.135) were high and positive in both expression patterns, showing no significant difference to the OS (p = 0.393). Conclusions: In our studies, c-MET high or HER2 negative expression was associated with a poorer OS. However, no direct correlation between HER2 and c-MET could be demonstrated

Vascularization of LBL structured nanofibrous matrices with endothelial cells for tissue regeneration

The aligned LBL scaffold promoted host vessel infiltration into the scaffolds and integration with in vitro prefabricated vascular structures.

Collagen-Platelet Composites Improve the Biomechanical Properties of Healing Anterior Cruciate Ligament Grafts in a Porcine Model

Background The outcome of anterior cruciate ligament (ACL) reconstruction is variable, and many patients have increased joint laxity postoperatively. Hypothesis Placement of a collagen-platelet composite (CPC) around the graft at the time of ACL reconstruction decreases postoperative knee laxity and improves the structural properties of the graft compared with standard ACL reconstruction. Study Design Controlled laboratory study. Methods Thirteen immature pigs underwent unilateral ACL reconstruction with a bone–patellar tendon–bone allograft. In 6 pigs, a standard allograft was used to reconstruct the ACL. In 7 pigs, a CPC was placed around the allograft. After 15 weeks of healing, the animals were euthanized, and the anterior-posterior (AP) knee laxity and structural properties of the graft were measured. Qualitative histology of the grafts was also performed. Results The AP laxity values of the reconstructed knees, normalized to the contralateral control, were significantly reduced by 28% and 57% at 60° and 90° of knee flexion, respectively, with the addition of CPC (P <. 001). Significant improvements in the graft structural properties were also found; the normalized yield (P =. 044) and maximum failure loads (P =. 025) of the CPC group were 60% higher than the standard ACL-reconstructed group. Although cellular and vessel infiltration were observed in the grafts of both groups, regions of necrosis were present only in the standard ACL-reconstructed group. Conclusion These data demonstrate that the application of CPC at the time of ACL reconstruction improves the structural properties of the graft and reduces early AP knee laxity in the porcine model after 15 weeks of healing. Clinical Relevance Application of a CPC to an ACL graft at the time of surgery decreased knee laxity and increased the structural properties of the graft after 15 weeks of healing.