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Abstract Background Endovascular therapy is an effective method for revascularization in lower extremity artery disease, but treating chronic total occlusion (CTO) remains challenging. This is particularly true for patients with severe calcification, poor run-off in below-the-knee arteries, or limited access sites, where even guidewire (GW) passage can be difficult and bidirectional approaches are often not feasible. The tip-detection (TD) method has been reported as a useful technique in coronary artery CTO interventions, allowing real-time visualization of the GW tip direction. Here, we applied the TD technique for peripheral CTO intervention. Case presentation Case 1 involved a 71-year-old man with a right toe ulcer. Angiography revealed total occlusion from the right anterior tibial artery (ATA) to the proximal dorsalis pedis artery. While attempting IVUS-guided parallel wiring, the GW could not advance through the intraplaque route because of severe calcification. We intentionally advanced the GW and IVUS into the subintimal space of the ATA to bypass the calcified lesion and performed IVUS-guided reentry using the TD technique in the distal ATA, where calcification was less severe. The second GW successfully passed through the intraplaque of the distal ATA and into the true lumen of the dorsalis pedis artery. Case 2 involved a 60-year-old man with bilateral intermittent claudication. Angiography revealed severe stenosis of the right common iliac artery (CIA) and CTO of the left CIA. Because of anatomical limitations and access site challenges, the antegrade approach for the left CIA was unsuccessful, and retrograde intraluminal wiring was difficult because of flexion and calcification. We advanced the GW and IVUS into the subintimal space and performed IVUS-guided reentry using the TD technique to access the true lumen of the proximal CIA. Finally, bilateral VBX stent grafts were implanted using the kissing stent technique. Conclusions IVUS-guided reentry wiring with the TD technique may offer a useful solution for passing complex peripheral CTO lesions in cases where only a uni-directional approach is feasible.

Abstract Background Hemostatic devices are now frequently used in femoral artery punctures, and the Angio-Seal (Terumo, Tokyo, Japan) is one of the most commonly used devices for closure of the femoral artery because it provides rapid hemostasis. Although device failure rarely occurs, if the collagen falls into the femoral artery, it may lead to severe limb ischemia. Herein, we describe a case of a novel endovascular technique for the treatment of Angio-Seal arterial closure device failure. Case presentation The patient in Case 1 was a 75-year-old man with severe left limb claudication. We used a contralateral antegrade approach and used the Angio-Seal for hemostasis. However, the Angio-Seal collagen and footplate dropped and stopped at the bifurcation of the superficial femoral artery and deep femoral artery. The collagen with the footplate was caught with myocardial biotome forceps (MBF) and pulled into the external iliac artery (EIA). The distal common femoral artery (CFA) was punctured, and we delivered a 10.0- × 80-mm stent (SMART®; Cordis, USA) to the EIA from the ipsilateral sheath. The stent was deployed at the EIA and crushed the collagen. The patient in Case 2 was an 88-year-old man with rest pain in the right limb. The right CFA was punctured using an ipsilateral approach and the Angio-Seal was used for hemostasis. The Angio-Seal collagen with the footplate dropped into the bifurcation of the deep femoral artery. The collagen and footplate were caught with MBF and pulled up to the EIA. The right CFA was punctured and a 10.0- × 60-mm stent (SMART®; Cordis) was delivered from the ipsilateral sheath. The stent was deployed at the EIA and crushed the collagen with the footplate. Conclusions MBF were used to grasp the dislodged collagen with the anchor and cover it with a stent at the iliac artery. This may be a useful bailout technique for Angio-Seal dislodgement.

In patients with a femoropopliteal chronic total occlusion (CTO) after femoro–femoral (FF) bypass surgery, it is often difficult to perform endovascular therapy because of access site problems. We have treated two patients with CTO of the superficial femoral artery (SFA) using an FF crossover bypass graft. The two cases were a man with intermittent claudication and acute limb ischemia, respectively. Enhanced computed tomography showed occlusion of the left SFA and the FF bypass previously performed was patent in both cases. We punctured the right common femoral artery and a guiding sheath was inserted to the left common femoral artery. A guidewire successfully passed through the intraplaque lesion by intravascular ultrasound-guided wiring in both cases. Revascularization was successfully achieved using drug-coated balloons and using drug-eluting stents, respectively. An FF crossover bypass graft may be a good access route for complex femoropopliteal cases, such as CTO lesions.

Abstract Messenger RNA (mRNA) therapy is the intracellular delivery of mRNA to produce desired therapeutic proteins. Developing strategies for local mRNA delivery is still required where direct intra‐articular injections are inappropriate for targeting a specific tissue. The mRNA delivery efficiency depends on protecting nucleic acids against nuclease‐mediated degradation and safe site‐specific intracellular delivery. Herein, novel mRNA‐releasing matrices based on RGD‐moiety‐rich gelatin methacryloyl (GelMA) microporous annealed particle (MAP) scaffolds are reported. GelMA concentration in aerogel‐based microgels (µgels) produced through a microfluidic process, MAP stiffnesses, and microporosity are crucial parameters for cell adhesion, spreading, and proliferation. After being loaded with mRNA complexes, MAP scaffolds composed of 10% GelMA µgels display excellent cell viability with increasing cell infiltration, adhesion, proliferation, and gene transfer. The intracellular delivery is achieved by the sustained release of mRNA complexes from MAP scaffolds and cell adhesion on mRNA‐releasing scaffolds. These findings highlight that hybrid systems can achieve efficient protein expression by delivering mRNA complexes, making them promising mRNA‐releasing biomaterials for tissue engineering.

Abstract Background Revascularization with endovascular therapy (EVT) for complex below-the-knee (BTK) chronic total occlusion (CTO) remains a challenging problem. The Japanese-BTK (J-BTK) CTO score is reported as an indicator of the difficulty of BTK CTO, with the guidewire (GW) passage success rate decreasing as the grade increases. We previously reported an effective GW crossing method for the intravascular ultrasound (IVUS)-guided parallel wiring of complex BTK CTO. In this study, we investigated the feasibility of EVT using IVUS-guided wiring for BTK CTO. Materials and methods This single center, retrospective study analyzed 65 consecutive BTK CTO vessels in which IVUS-guided wiring was attempted after the failure of a conventional antegrade wiring approach from November 2020 to November 2022. The primary endpoint was the clinical success of the target CTO vessel. The secondary endpoints were the GW success rate per grade based on the J-BTK CTO score, number of GW used for CTO crossing, fluoroscopy time, and complications. Results Target vessels were the anterior tibial artery (66.2% of cases), peroneal artery (9.2%), and posterior tibial artery (24.6%). Blunt type CTO entry was performed in 55.4% of cases, calcification of entry was observed in 24.6% of cases, the mean occlusion length was 228.2 ± 93.7 mm, mean reference vessel diameter was 2.1 ± 0.71 mm, and outflow was absent in 38.5% of cases. J-BTK CTO scores of 0/1 (grade A), 2/3 (grade B), 4/5 (grade C), and 6 (grade D) were seen in 18.5%, 43.1%, 36.3%, and 1.5% of cases, respectively. The clinical success rate was 95.4%. The GW success rate by J-BTK CTO grade was as follows: grade A (100%), B (100%), C (91.7%), and D (0%). The mean number of GW used was 3.4 ± 1.4, the mean fluoroscopy time was 72.3 ± 32.5 min, and complications occurred in 7.7% of cases. Conclusion This study showed a very high clinical success rate despite the difficulty of BTK CTO. IVUS-guided EVT might be a feasible strategy for complex BTK CTO.

Abstract New vaccine platforms that activate humoral immunity and generate neutralizing antibodies are required to combat emerging pathogens, including influenza virus. A slurry of antigen‐loaded hydrogel microparticles that anneal to form a porous scaffold with high surface area for antigen uptake by infiltrating immune cells as the biomaterial degrades is demonstrated to enhance humoral immunity. Antigen‐loaded‐microgels elicited a robust cellular humoral immune response, with increased CD4+ T follicular helper (Tfh) cells and prolonged germinal center (GC) B cells comparable to the commonly used adjuvant, aluminum hydroxide (Alum). Increasing the weight fraction of polymer material led to increased material stiffness and antigen‐specific antibody titers superior to Alum. Vaccinating mice with inactivated influenza virus loaded into this more highly cross‐linked formulation elicited a strong antibody response and provided protection against a high dose viral challenge. By tuning physical and chemical properties, adjuvanticity can be enhanced leading to humoral immunity and protection against a pathogen, leveraging two different types of antigenic material: individual protein antigen and inactivated virus. The flexibility of the platform may enable design of new vaccines to enhance innate and adaptive immune cell programming to generate and tune high affinity antibodies, a promising approach to generate long‐lasting immunity.