A multicenter prospective observational study appraising the effectiveness of the Supera stent after subintimal recanalization of femoro-popliteal artery occlusion: The SUPERSUB II study.

BACKGROUND: Complex femoropopliteal artery disease represents a challenge. The Supera stent holds the promise of improving the results of endovascular therapy for complex femoropopliteal disease. AIMS: We aimed at appraising the early and long-term effectiveness of the Supera stent after successful subintimal angioplasty (SuperSUB strategy) for complex femoropopliteal lesions. METHODS: We conducted a multicenter, prospective, single-arm observational study including consecutive patients at participating centers in whom Supera was implanted after successful subintimal angioplasty for complex femoropopliteal lesions. RESULTS: A total of 92 patients were included Femoropopliteal arteries were the most common target, and lesion length was 261 ± 102 mm. Most procedures were technically demanding, with antegrade femoral access in 35 (38%) and retrograde distal access in 55 (60%). Supera stent length was 281 ± 111 mm, with 4, 5, and 6 mm devices being most commonly used: 32 (35%), 35 (38%), and 23 (25%), respectively. Technical success was achieved in 100% of subjects, as was clinical success (per subject), whereas procedural success (per subject) was obtained in 98%. At 24 months, freedom from clinically driven target lesion revascularization was 93%, whereas primary patency was 87%. When compared with a similar historical cohort, Supera stent use appeared to be associated with a reduction in resources. CONCLUSION: Use of Supera stent after successful subintimal recanalization of complex lower limb arterial lesions yields favorable procedural results, which are maintained over follow-up, and are associated also with a favorable resource use profile.

Development and preclinical evaluation of bioactive nerve conduits for peripheral nerve regeneration: A comparative study.

In severe peripheral nerve injuries, nerve conduits (NCs) are good alternatives to autografts/allografts; however, the results the available devices guarantee for are still not fully satisfactory. Herein, differently bioactivated NCs based on the new polymer oxidized polyvinyl alcohol (OxPVA) are compared in a rat model of sciatic nerve neurotmesis (gap: 5 mm; end point: 6 weeks). Thirty Sprague Dawley rats are randomized to 6 groups: Reverse Autograft (RA); Reaxon®; OxPVA; OxPVA + EAK (self-assembling peptide, mechanical incorporation); OxPVA + EAK-YIGSR (mechanical incorporation); OxPVA + Nerve Growth Factor (NGF) (adsorption). Preliminarily, all OxPVA-based devices are comparable with Reaxon® in Sciatic Functional Index score and gait analysis; moreover, all conduits sustain nerve regeneration (S100, ß-tubulin) without showing substantial inflammation (CD3, F4/80) evidences. Following morphometric analyses, OxPVA confirms its potential in PNI repair (comparable with Reaxon®) whereas OxPVA + EAK-YIGSR stands out for its myelinated axons total number and density, revealing promising in injury recovery and for future application in clinical practice.

Immediate Effects of Extracorporeal Shock Wave Therapy in Fascial Fibroblasts: An In Vitro Study.

Extracorporeal shock waves (ESWs) are used in the treatment of soft tissue injuries, but their role in the treatment of myofascial pain has not yet been demonstrated. The aim of this study was to investigate changes in cell biology of fibroblasts derived from deep/muscular fascia following treatment with ESWs. Primary fascial fibroblasts were collected from small samples of human fascia lata of the thigh of three volunteer patients (two men, one woman) during orthopedic surgery, and put in culture. These cells were exposed to 100 impulses of 0.05 mJ/mm2 with a frequency of 2.5 Hz, using 3D-printed support. This study demonstrated for the first time that ESWs can lead to in vitro production of hyaluronan-rich vesicles immediately after the treatment. At 1, 4, and 24 h after treatment, Alcian blue and Toluidine blue staining; immunocytochemistry to detect hyaluronic acid binding protein (HABP), collagen I, and collagen III; and transmission electron microscopy demonstrated that these vesicles are rich in hyaluronan and collagen I and III. The diameter of these vesicles was assessed, highlighting a small size at 1 h after ESW treatment, whereas at 4 and 24 h, they had an increase in the size. Particularly evident was the release of hyaluronan-rich vesicles, collagen-I, and collagen-III starting at 1 h, with an increase at 4 h and maintenance by 24 h. These in vitro data indicate that fascial cells respond to ESW treatment by regulating and remodeling the formation of extracellular matrix.

Meniscus regeneration by 3D printing technologies: Current advances and future perspectives.

Meniscal tears are a frequent orthopedic injury commonly managed by conservative strategies to avoid osteoarthritis development descending from altered biomechanics. Among cutting-edge approaches in tissue engineering, 3D printing technologies are extremely promising guaranteeing for complex biomimetic architectures mimicking native tissues. Considering the anisotropic characteristics of the menisci, and the ability of printing over structural control, it descends the intriguing potential of such vanguard techniques to meet individual joints' requirements within personalized medicine. This literature review provides a state-of-the-art on 3D printing for meniscus reconstruction. Experiences in printing materials/technologies, scaffold types, augmentation strategies, cellular conditioning have been compared/discussed; outcomes of pre-clinical studies allowed for further considerations. To date, translation to clinic of 3D printed meniscal devices is still a challenge: meniscus reconstruction is once again clear expression of how the integration of different expertise (e.g., anatomy, engineering, biomaterials science, cell biology, and medicine) is required to successfully address native tissues complexities.

Bioactivated Oxidized Polyvinyl Alcohol towards Next-Generation Nerve Conduits Development.

The limitations and difficulties that nerve autografts create in normal nerve function recovery after injury is driving research towards using smart materials for next generation nerve conduits (NCs) setup. Here, the new polymer partially oxidized polyvinyl alcohol (OxPVA) was assayed to verify its future potential as a bioactivated platform for advanced/effective NCs. OxPVA-patterned scaffolds (obtained by a 3D-printed mold) with/without biochemical cues (peptide IKVAV covalently bound (OxPVA-IKVAV) or self-assembling peptide EAK (sequence: AEAEAKAKAEAEAKAK), mechanically incorporated (OxPVA+EAK) versus non-bioactivated scaffold (peptide-free OxPVA (PF-OxPVA) supports, OxPVA without IKVAV and OxPVA without EAK control scaffolds) were compared for their biological effect on neuronal SH-SY5Y cells. After cell seeding, adhesion/proliferation, mediated by (a) precise control over scaffolds surface ultrastructure; (b) functionalization efficacy guaranteed by bioactive cues (IKVAV/EAK), was investigated by MTT assay at 3, 7, 14 and 21 days. As shown by the results, the patterned groove alone stimulates colonization by cells; however, differences were observed when comparing the scaffold types over time. In the long period (21 days), patterned OxPVA+EAK scaffolds distinguished in bioactivity, assuring a significantly higher total cell amount than the other groups. Experimental evidence suggests patterned OxPVA-EAK potential for NCs device fabrication.

3D Reconstruction of the Morpho-Functional Topography of the Human Vagal Trigone.

The Vagal Trigone, often referred to as Ala Cinerea, is a triangular-shaped area of the floor of the fourth ventricle that is strictly involved in the network of chardiochronotropic, baroceptive, respiratory, and gastrointestinal control systems of the medulla oblongata. While it is frequently identified as the superficial landmark for the underlying Dorsal Motor Nucleus of the Vagus, this correspondence is not univocal in anatomical literature and is often oversimplified in neuroanatomy textbooks and neurosurgical atlases. As the structure represents an important landmark for neurosurgical procedures involving the floor of the fourth ventricle, accurate morphological characterization is required to avoid unwanted side effects (e.g., bradychardia, hypertension) during neuorphysiological monitoring and cranial nerve nuclei stimulation in intraoperative settings. The aim of this study was to address the anatomo-topographical relationships of the Vagal Trigone with the underlying nuclei. For this purpose, we have conducted an anatomo-microscopical examination of serial sections deriving from 54 Human Brainstems followed by 3D reconstruction and rendering of the specimens. Our findings indicate that the Vagal Trigone corresponds only partially with the Dorsal Motor Nucleus of the Vagus, while most of its axial profile is occupied by the dorsal regions of the Solitary Tract Nucleus. Furthermore, basing on literature and our findings we speculate that the neuroblasts of the Dorsal Motor Nucleus of the Vagus undergo neurobiotaxic migration induced by the neuroblasts of the dorsolaterally located solitary tract nucleus, giving rise to the Ala Cinerea, a topographically defined area for parasympathetic visceral control.

Development of Oxidized Polyvinyl Alcohol-Based Nerve Conduits Coupled with the Ciliary Neurotrophic Factor.

Functionalized synthetic conduits represent a promising strategy to enhance peripheral nerve regeneration by guiding axon growth while delivering therapeutic neurotrophic factors. In this work, hollow nerve conduits made of polyvinyl alcohol partially oxidized with bromine (OxPVA_Br2) and potassium permanganate (OxPVA_KMnO4) were investigated for their structural/biological properties and ability to absorb/release the ciliary neurotrophic factor (CNTF). Chemical oxidation enhanced water uptake capacity of the polymer, with maximum swelling index of 60.5% ± 2.5%, 71.3% ± 3.6% and 19.5% ± 4.0% for OxPVA_Br2, OxPVA_KMnO4 and PVA, respectively. Accordingly, hydrogel porosity increased from 15.27% ± 1.16% (PVA) to 62.71% ± 8.63% (OxPVA_Br2) or 77.50% ± 3.39% (OxPVA_KMnO4) after oxidation. Besides proving that oxidized PVA conduits exhibited mechanical resistance and a suture holding ability, they did not exert a cytotoxic effect on SH-SY5Y and Schwann cells and biodegraded over time when subjected to enzymatic digestion, functionalization with CNTF was performed. Interestingly, higher amounts of neurotrophic factor were detected in the lumen of OxPVA_Br2 (0.22 ± 0.029 µg) and OxPVA_KMnO4 (0.29 ± 0.033 µg) guides rather than PVA (0.11 ± 0.021 µg) tubular scaffolds. In conclusion, we defined a promising technology to obtain drug delivery conduits based on functionalizable oxidized PVA hydrogels.