Safety and Effectiveness of Abre Self-Expanding Venous Stent for Treatment of Superior Vena Cava Syndrome.

PURPOSE: Superior vena cava (SVC) syndrome is a constellation of symptoms that results from partial or complete SVC obstruction. Endovascular SVC stenting is an effective treatment for SVC syndrome with rapid clinical efficacy and low risk of complications. In this study, we assess the technical and clinical outcomes of a cohort of patients with SVC syndrome treated with the AbreTM self-expanding venous stent (Medtronic, Inc, Minneapolis, MN, USA). METHODS: An institutional database was used to retrospectively identify patients with SVC syndrome treated with AbreTM venous self-expanding stent placement between 2021-2023. Patient demographic data, technical outcomes, treatment effectiveness, and adverse events were obtained from the electronic medical record. Nineteen patients (mean age 58.6) were included in the study. Thirteen interventions were performed for malignant compression of the SVC, 5 for central venous catheter-related SVC stenosis, and 1 for HD fistula-related SVC stenosis refractory to angioplasty. RESULTS: Primary patency was achieved in 93% of patients (17/19). Two patients (7%) required re-intervention with thrombolysis and angioplasty within 30 days post-stenting. Mean duration of clinical and imaging follow-up were 228.7 ± 52.7 and 258.7 ± 62.1 days, respectively. All patients with clinical follow-up experienced significant improvement in clinical symptoms post-intervention. No stent related complications were identified post-intervention. CONCLUSIONS: Treatment of SVC syndrome with the AbreTM self-expanding venous stent has high rates of technical and clinical success. No complications related to stent placement were identified in this study.

The clinician-AI interface: intended use and explainability in FDA-cleared AI devices for medical image interpretation.

As applications of AI in medicine continue to expand, there is an increasing focus on integration into clinical practice. An underappreciated aspect of this clinical translation is where the AI fits into the clinical workflow, and in turn, the outputs generated by the AI to facilitate clinician interaction in this workflow. For instance, in the canonical use case of AI for medical image interpretation, the AI could prioritize cases before clinician review or even autonomously interpret the images without clinician review. A related aspect is explainability - does the AI generate outputs to help explain its predictions to clinicians? While many clinical AI workflows and explainability techniques have been proposed, a summative assessment of the current scope in clinical practice is lacking. Here, we evaluate the current state of FDA-cleared AI devices for medical image interpretation assistance in terms of intended clinical use, outputs generated, and types of explainability offered. We create a curated database focused on these aspects of the clinician-AI interface, where we find a high frequency of "triage" devices, notable variability in output characteristics across products, and often limited explainability of AI predictions. Altogether, we aim to increase transparency of the current landscape of the clinician-AI interface and highlight the need to rigorously assess which strategies ultimately lead to the best clinical outcomes.

Active tissue adhesive activates mechanosensors and prevents muscle atrophy.

While mechanical stimulation is known to regulate a wide range of biological processes at the cellular and tissue levels, its medical use for tissue regeneration and rehabilitation has been limited by the availability of suitable devices. Here we present a mechanically active gel-elastomer-nitinol tissue adhesive (MAGENTA) that generates and delivers muscle-contraction-mimicking stimulation to a target tissue with programmed strength and frequency. MAGENTA consists of a shape memory alloy spring that enables actuation up to 40% strain, and an adhesive that efficiently transmits the actuation to the underlying tissue. MAGENTA activates mechanosensing pathways involving yes-associated protein and myocardin-related transcription factor A, and increases the rate of muscle protein synthesis. Disuse muscles treated with MAGENTA exhibit greater size and weight, and generate higher forces compared to untreated muscles, demonstrating the prevention of atrophy. MAGENTA thus has promising applications in the treatment of muscle atrophy and regenerative medicine.

Skeletal muscle regeneration with robotic actuation-mediated clearance of neutrophils.

Mechanical stimulation (mechanotherapy) can promote skeletal muscle repair, but a lack of reproducible protocols and mechanistic understanding of the relation between mechanical cues and tissue regeneration limit progress in this field. To address these gaps, we developed a robotic device equipped with real-time force control and compatible with ultrasound imaging for tissue strain analysis. We investigated the hypothesis that specific mechanical loading improves tissue repair by modulating inflammatory responses that regulate skeletal muscle regeneration. We report that cyclic compressive loading within a specific range of forces substantially improves functional recovery of severely injured muscle in mice. This improvement is attributable in part to rapid clearance of neutrophil populations and neutrophil-mediated factors, which otherwise may impede myogenesis. Insights from this work will help advance therapeutic strategies for tissue regeneration broadly.

Rheological characterization, compression, and injection molding of hydroxyapatite-silk fibroin composites.

Traditional bone fixation devices made from inert metal alloys provide structural strength for bone repair but are limited in their ability to actively promote bone healing. Although several naturally derived bioactive materials have been developed to promote ossification in bone defects, it is difficult to translate small-scale benchtop fabrication of these materials to high-output manufacturing. Standard industrial molding processes, such as injection and compression molding, have typically been limited to use with synthetic polymers since most biopolymers cannot withstand the harsh processing conditions involved in these techniques. Here we demonstrate injection and compression molding of a bioceramic composite comprised of hydroxyapatite (HA) and silk fibroin (SF) from Bombyx mori silkworm cocoons. Both the molding behavior of the HA-SF slurry and final scaffold mechanics can be controlled by modulating SF protein molecular weight, SF content, and powder-to-liquid ratio. HA-SF composites with up to 20 weight percent SF were successfully molded into stable three-dimensional structures using high pressure molding techniques. The unique durability of silk fibroin enables application of common molding techniques to fabricate composite silk-ceramic scaffolds. This work demonstrates the potential to move bone tissue engineering one step closer to large-scale manufacturing of natural protein-based resorbable bone grafts and fixation devices.

Regenerating Antithrombotic Surfaces through Nucleic Acid Displacement.

Blood-contacting devices are commonly coated with antithrombotic agents to prevent clot formation and to extend the lifespan of the device. However, in vivo degradation of these bioactive surface agents ultimately limits device efficacy and longevity. Here, a regenerative antithrombotic catheter surface treatment is developed using oligodeoxynucleotide (ODN) toehold exchange. ODN strands modified to carry antithrombotic payloads can inhibit the thrombin enzyme when bound to a surface and exchange with rapid kinetics over multiple cycles, even while carrying large payloads. The surface-bound ODNs inhibit thrombin activity to significantly reduce fibrinogen cleavage and fibrin formation, and this effect is sustained after ODN exchange of the surface-bound strands with a fresh antithrombotic payload. This study presents a unique strategy for achieving a continuous antithrombotic state for blood-contacting devices using an ODN-based regeneration method.

Silk microfiber-reinforced silk hydrogel composites for functional cartilage tissue repair.

Cartilage tissue lacks an intrinsic capacity for self-regeneration due to slow matrix turnover, a limited supply of mature chondrocytes and insufficient vasculature. Although cartilage tissue engineering has achieved some success using agarose as a scaffolding material, major challenges of agarose-based cartilage repair, including non-degradability, poor tissue-scaffold integration and limited processing capability, have prompted the search for an alternative biomaterial. In this study, silk fiber-hydrogel composites (SF-silk hydrogels) made from silk microfibers and silk hydrogels were investigated for their potential use as a support material for engineered cartilage. We demonstrated the use of 100% silk-based fiber-hydrogel composite scaffolds for the development of cartilage constructs with properties comparable to those made with agarose. Cartilage constructs with an equilibrium modulus in the native tissue range were fabricated by mimicking the collagen fiber and proteoglycan composite architecture of native cartilage using biocompatible, biodegradable silk fibroin from Bombyx mori. Excellent chondrocyte response was observed on SF-silk hydrogels, and fiber reinforcement resulted in the development of more mechanically robust constructs after 42 days in culture compared to silk hydrogels alone. Thus, we demonstrate the versatility of silk fibroin as a composite scaffolding material for use in cartilage tissue repair to create functional cartilage constructs that overcome the limitations of agarose biomaterials, and provide a much-needed alternative to the agarose standard.

Clinical applications of naturally derived biopolymer-based scaffolds for regenerative medicine.

Naturally derived polymeric biomaterials, such as collagens, silks, elastins, alginates, and fibrins are utilized in tissue engineering due to their biocompatibility, bioactivity, and tunable mechanical and degradation kinetics. The use of these natural biopolymers in biomedical applications is advantageous because they do not release cytotoxic degradation products, are often processed using environmentally-friendly aqueous-based methods, and their degradation rates within biological systems can be manipulated by modifying the starting formulation or processing conditions. For these reasons, many recent in vivo investigations and FDA-approval of new biomaterials for clinical use have utilized natural biopolymers as matrices for cell delivery and as scaffolds for cell-free support of native tissues. This review highlights biopolymer-based scaffolds used in clinical applications for the regeneration and repair of native tissues, with a focus on bone, skeletal muscle, peripheral nerve, cardiac muscle, and cornea substitutes.

Silk as a biocohesive sacrificial binder in the fabrication of hydroxyapatite load bearing scaffolds.

Limitations of current clinical methods for bone repair continue to fuel the demand for a high strength, bioactive bone replacement material. Recent attempts to produce porous scaffolds for bone regeneration have been limited by the intrinsic weakness associated with high porosity materials. In this study, ceramic scaffold fabrication techniques for potential use in load-bearing bone repairs have been developed using naturally derived silk from Bombyx mori. Silk was first employed for ceramic grain consolidation during green body formation, and later as a sacrificial polymer to impart porosity during sintering. These techniques allowed preparation of hydroxyapatite (HA) scaffolds that exhibited a wide range of mechanical and porosity profiles, with some displaying unusually high compressive strength up to 152.4 ± 9.1 MPa. Results showed that the scaffolds exhibited a wide range of compressive strengths and moduli (8.7 ± 2.7 MPa to 152.4 ± 9.1 MPa and 0.3 ± 0.1 GPa to 8.6 ± 0.3 GPa) with total porosities of up to 62.9 ± 2.7% depending on the parameters used for fabrication. Moreover, HA-silk scaffolds could be molded into large, complex shapes, and further machined post-sinter to generate specific three-dimensional geometries. Scaffolds supported bone marrow-derived mesenchymal stem cell attachment and proliferation, with no signs of cytotoxicity. Therefore, silk-fabricated HA scaffolds show promise for load bearing bone repair and regeneration needs.