Clinical comparative analysis of 3D printing-assisted extracorporeal pre-fenestration and Castor integrated branch stent techniques in treating type B aortic dissections with inadequate proximal landing zones.

BACKGROUND: This study aims to compare the clinical effects of two distinct surgical approaches, namely 3D printing-assisted extracorporeal pre-fenestration and Castor integrated branch stent techniques, in treating patients with Stanford type B aortic dissections (TBAD) characterized by inadequate proximal landing zones. METHODS: A retrospective analysis was conducted on 84 patients with type B aortic dissection (TBAD) who underwent thoracic endovascular aortic repair (TEVAR) with left subclavian artery (LSA) reconstruction at our center from January 2022 to July 2023. Based on the different surgical approaches, the patients were divided into two groups: the group assisted by 3D printing for extracorporeal pre-fenestration (n = 44) and the group using the castor integrated branch stent (n = 40). Clinical indicators: including general patient information, operative time, surgical success rate, intraoperative and postoperative complication rates, re-intervention rate, and mortality, as well as postoperative aortic remodeling, were compared between the two groups. The endpoint of this study is the post-TEVAR mortality rate in patients. RESULTS: The surgical success rate and device deployment success rate were 100% in both groups, with no statistically significant difference (P > 0.05). However, the group assisted by 3D printing for extracorporeal pre-fenestration had a significantly longer operative time (184.20 ± 54.857 min) compared to the group using the castor integrated branch stent (152.75 ± 33.068 min), with a statistically significant difference (t = 3.215, p = 0.002, P < 0.05). Moreover, the incidence of postoperative cerebral infarction and beak sign was significantly lower in the group assisted by 3D printing for extracorporeal pre-fenestration compared to the castor-integrated branch stent group, demonstrating statistical significance. There were no significant differences between the two groups in terms of other postoperative complication rates and aortic remodeling (P > 0.05). Notably, computed tomography angiography images revealed the expansion of the vascular true lumen and the reduction of the false lumen at three specified levels of the thoracic aorta. The follow-up duration did not show any statistically significant difference between the two groups (10.59 ± 4.52 vs. 9.08 ± 4.35 months, t = 1.561, p = 0.122 > 0.05). Throughout the follow-up period, neither group experienced new endoleaks, spinal cord injuries, nor limb ischemia. In the castor-integrated branch stent group, one patient developed a new distal dissection, prompting further follow-up. Additionally, there was one case of mortality due to COVID-19 in each group. There were no statistically significant differences between the two groups in terms of re-intervention rate and survival rate (P > 0.05). CONCLUSION: Both 3D printing-assisted extracorporeal pre-fenestration TEVAR and castor-integrated branch stent techniques demonstrate good safety and efficacy in treating Stanford type B aortic dissection with inadequate proximal anchoring. The 3D printing-assisted extracorporeal pre-fenestration TEVAR technique has a lower incidence of postoperative cerebral infarction and beak sign, while the castor-integrated branch stent technique has advantages in operative time.

3D Printing-Assisted versus Conventional Extracorporeal Fenestration Tevar for Stanford Type B Arteries Dissection with Undesirable Proximal Anchoring Zone: Efficacy Analysis.

BACKGROUND: To compare the outcomes of two Thoracic Endovascular Aortic Repair (TEVAR) techniques of Left Subclavian Artery (LSA) reconstruction for Stanford Type B Aortic Dissection (TBAD) patients with undesirable proximal anchoring zone. METHODS: We retrospectively reviewed 57 patients with TBAD who underwent either three dimensional (3D)-printing-assisted extracorporeal fenestration (n = 32) or conventional extracorporeal fenestration (n = 25) from December 2021 to January 2023. We compared their demographic characteristics, operative time, technical success rate, complication rate, secondary intervention rate, mortality rate, and aortic remodeling. RESULTS: Compared with the conventional group, the 3D-printing-assisted group had a significantly shorter operative time (147.84 ± 33.94 min vs. 223.40 ± 65.93 min, p < 0.001), a significantly lower rate of immediate endoleak (3.1% vs. 24%, p = 0.048) and a significantly higher rate of true lumen diameter expansion in the stent-graft segment (all p < 0.05), but a significantly longer stent graft modification time (37.63 ± 2.99 min vs. 28.4 ± 2.12 min, p < 0.001). There were no significant differences in other outcomes between the two groups (p > 0.05). The degree of false lumen thrombosis was higher in the stent-graft segment than in the non-stent-graft segment in both groups and the difference was statistically significant (X2 = 5.390, 4.878; p = 0.02, 0.027). CONCLUSIONS: Both techniques are safe and effective for TBAD with an undesirable proximal landing zone. The 3D-printing-assisted extracorporeal fenestration TEVAR technique has advantages in operative time, endoleak risk, and aortic remodeling, while the traditional extracorporeal fenestration TEVAR technique has advantages in stent modification.

To Explore the Effect of Preoperative Hemodynamic Factors on The Outcome of Pseudolumen After Stanford Type B Aortic Dissection TEVAR Based on Computer Fluid Dynamics.

OBJECTIVE: The preoperative aortic hemodynamic data of patients with Stanford type B aortic dissection were obtained by computer fluid dynamics (CFD). Then we explored the relationship between hemodynamic data and short-term residual pseudolumen after thoracic endovascular aortic repair (TEVAR) and predict the latter through the former. METHODS: We collected the relevant data of 53 patients who underwent TEVAR in our hospital. They were divided into the A group (residual false lumen group) and B group (closed false lumen group), according to whether there was a residual false cavity around the stent recently after TEVAR. Three-dimensional reconstruction and CFD analysis of the thoracic and abdominal aorta was performed by DSCTA before the operation to obtain the aortic wall shear stress (WSS) and maximum blood flow velocity of the true and false lumen at the entrance, middle point of the long axis, and distal decompression port at the peak time of ventricular systolic velocity. Through the statistical analysis, we further studied the predictive value of hemodynamic data for residual pseudolumen. RESULTS: There was no significant difference in age, male, preoperative and postoperative thoracic and abdominal aorta DSCTA interval, history of hypertension, history of diabetes, smoking, Pt and APTT at admission between the two groups (P > 0.05). The blood flow velocity and shear stress at the entrance of the false lumen and the distal decompression port in the two groups were statistically significant (P < 0.05), while the other hemodynamic indexes were not statistically significant (P > 0.05). Binary logistic regression analysis further showed that the shear stress of the false lumen at the level of the distal decompression port (OR = 1.73, P = 0.01) was an independent risk factor for the residual false lumen around the stent in the early stage after TEVAR. The ROC curve analysis showed that the AUC area of the ROC curve corresponding to the shear stress of the false cavity at the level of the distal decompression port was 0.83, the best cross-sectional value was 9.49pa, and the sensitivity and specificity were 84.60% and 72.50%. CONCLUSIONS: The residual pseudolumen after TEVAR is related to the hemodynamic factors in the aorta before TEVAR. Preoperative hemodynamic data also have good predictive value. When the shear stress of the false lumen at the level of the distal decompression port is greater than 9.49pa, the probability of residual false lumen around the stent during the perioperative period significantly increases.

Construction of Degradable and Amphiphilic Triblock Polymer Carriers for Effective Delivery of siRNA.

The development of effective and safe delivery carriers is one of the prerequisites for the clinical translation of siRNA-based therapeutics. In this study, a library of 144 functional triblock polymers using ring-opening polymerization (ROP) and thiol-ene click reaction is constructed. These triblock polymers are composed of hydrophilic poly (ethylene oxide) (PEO), hydrophobic poly (ε-caprolactone) (PCL), and cationic amine blocks. Three effective carriers are discovered by high-throughput screening of these polymers for siRNA delivery to HeLa-Luc cells. In vitro evaluation shows that siLuc-loaded nanoparticles (NPs) fabricated with leading polymer carriers exhibit sufficient knockdown of luciferase genes and relatively low cytotoxicity. The chemical structure of polymers significantly affects the physicochemical properties of the resulting siRNA-loaded NPs, which leads to different cellular uptake of NPs and endosomal escape of loaded siRNA and thus the overall in vitro siRNA delivery efficacy. After systemic administration to mice with xenograft tumors, siRNA NPs based on P2-4.5A8 are substantially accumulated at tumor sites, suggesting that PEO and PCL blocks are beneficial for improving blood circulation and biodistribution of siRNA NPs. This functional triblock polymer platform may have great potential in the development of siRNA-based therapies for the treatment of cancers.

Improved paclitaxel delivery with PEG-b-PLA/zein nanoparticles prepared via flash nanoprecipitation.

Polymeric micelle is a promising vehicle to improve the bioavailability and clinical outcomes of paclitaxel (PTX) which has been proven effective in the treatment of a wide range of cancers. However, conventional PTX formulation with the amphiphilic PEG-b-PLA usually suffers from insufficient PTX loading, low stability of PTX-micelles, and rapid PTX release due to low compatibility between PTX and PLA, limiting its clinical application. In this study, a novel nanoparticle platform was developed to improve the stability of PTX-loaded nanoparticles (NPs) and the delivery efficacy of PTX by integrating the flash nanoprecipitation (FNP) technique and a combination of amphiphilic PEG-PLA and super hydrophobic zein. The incorporation of zein led to the formation of distinct hydrophobic interiors of NPs which enhanced the interaction between PTX and NPs, therefore improving the encapsulation efficiency of PTX and sustained drug release compared with PEG-PLA micelles without zein. In addition, FNP allowed facile fabrication of PTX-NPs with smaller sizes and higher stability. These PTX-NPs showed superior sustained release of PTX and good cancer cell-killing in vitro. Among them, PTX-5k-16k-1Z NPs exhibited excellent biosafety and anti-tumor efficacy in a xenograft tumor model in mice, suggesting great potential in the delivery of hydrophobic drugs for cancer therapy.

mRNA delivery via non-viral carriers for biomedical applications.

As an emerging new class of nucleic acid drugs, messenger RNA (mRNA) has huge potential in immunotherapy, regenerative medicine, vaccine, and gene editing. Comparing with siRNA and pDNA, mRNA is more vulnerable to nucleases in vivo. However, the lack of effective and safe delivery methods impedes the broad application of mRNA-based therapeutics. Up to now, the delivery of mRNA remains largely unexplored, and therefore, is a hot topic in the field of gene therapy. In this review, we will summarize the ongoing challenges in mRNA-based therapeutics and unmet requirements for delivery vehicles in terms of the unique structure of mRNA. We then highlight the advancement in mRNA delivery in both fundamental research and clinical applications. Finally, a prospective will be proposed upon reviewing the current progress in mRNA delivery.

Tumor-targeting peptide functionalized PEG-PLA micelles for efficient drug delivery.

Because of their excellent capacity to significantly improve the bioavailability and solubility of chemotherapy drugs, block copolymer micelles are widely utilized for chemotherapy drug delivery. In order to further improve the anti-tumor ability and reduce unwanted side effects of drugs, tumor-targeting peptides were used to functionalize the surface of polymer micelles so that the micelles can target tumor tissues. Herein, we synthesized a kind of PEG-PLA that is maleimide-terminated and then conjugated with a specific peptide F3 which revealed specific capacity binding to nucleolin that is overexpressed on the surface of many tumor cells. Then, F3 conjugated, paclitaxel loaded nanoparticles (F3-NP-PTX) were prepared as stable micelles that displayed an enhanced accumulation via a peptide-mediated cellular association in human breast cancer cells (MCF-7). Furthermore, F3-NP-PTX showed a prominent anti-tumor efficacy compared with non-targeting nanoparticles (NP-PTX) both in vitro and in vivo, and showed great potential as an efficacious targeting drug delivery system for breast cancer treatment.

Effect of low-level laser irradiation on oxygen free radicals and ventricular remodeling in the infarcted rat heart.

OBJECTIVE: The purpose of this study was to assess the effects of low-level laser irradiation (LLLI) on the expression of oxygen free radicals (OFR) and ventricular remodeling (VR) in the model of rat myocardial infarction (RMMI). BACKGROUND DATA: LLLI reduces the infarct size and formation of scar tissue in the rat heart after myocardial infarction (MI). However, the exact mechanism has not been demonstrated so far. METHODS: RMMI was induced by ligating the left anterior descending coronary artery (LAD). After 3 weeks, LLLI (635 nm, 6 mW laser, 7.64 mW/cm(2), 125 sec, 0.96 J/cm(2)) was applied to the surface of heart directly. Four to six rats were euthanized at 1 h, 24 h, 48 h, 72 h, and 1 week after LLLI, and the infarcted myocardia were excised for the measurement of the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA). At the end of 4 weeks after MI, the hearts were harvested for histological analysis. RESULTS: Myocardial SOD activity with LLLI was lower compared with control (p<0.05), and myocardial MDA content with LLLI was higher compared with control (p<0.05), at all the time points. In all rats, the activity of SOD was down to the minimum and the content of MDA was up to the peak at 48 h after laser irradiation. The infarct size was reduced (35±10% vs. 18±9%, p<0.05), the left ventricular wall thickness was increased (0.31±0.03 vs. 0.84±0.02 mm, p<0.05) and the percentage of collagen fibers in the infarcted area was attenuated (64.34±2.20% vs. 30.97±2.60%) by LLLI. CONCLUSIONS: LLLI could cause OFR accumulation, reduce infarct size, increase ventricular wall thickness, and attenuate the formation of collagen fibers, suggesting the beneficial effects of LLLI on improvement of VR after MI.