P-Selectin mediates targeting of a self-assembling phototherapeutic nanovehicle enclosing dipyridamole for managing thromboses.

Thrombotic vascular disorders, specifically thromboembolisms, have a significant detrimental effect on public health. Despite the numerous thrombolytic and antithrombotic drugs available, their efficacy in penetrating thrombus formations is limited, and they carry a high risk of promoting bleeding. Consequently, the current medication dosage protocols are inadequate for preventing thrombus formation, and higher doses are necessary to achieve sufficient prevention. By integrating phototherapy with antithrombotic therapy, this study addresses difficulties related to thrombus-targeted drug delivery. We developed self-assembling nanoparticles (NPs) through the optimization of a co-assembly engineering process. These NPs, called DIP-FU-PPy NPs, consist of polypyrrole (PPy), dipyridamole (DIP), and P-selectin-targeted fucoidan (FU) and are designed to be delivered directly to thrombi. DIP-FU-PPy NPs are proposed to offer various potentials, encompassing drug-loading capability, targeted accumulation in thrombus sites, near-infrared (NIR) photothermal-enhanced thrombus management with therapeutic efficacy, and prevention of rethrombosis. As predicted, DIP-FU-PPy NPs prevented thrombus recurrence and emitted visible fluorescence signals during thrombus clot penetration with no adverse effects. Our co-delivery nano-platform is a simple and versatile solution for NIR-phototherapeutic multimodal thrombus control.

Long-Term Complications of Cranioplasty Using Stored Autologous Bone Graft, Three-Dimensional Polymethyl Methacrylate, or Titanium Mesh After Decompressive Craniectomy: A Single-Center Experience After 596 Procedures.

OBJECTIVE: Cranioplasty is a technically simple procedure intended to repair defects of the skull to provide protection after craniectomy, improve functional outcomes, and restore cosmesis. Several materials have been used for the restoration of skull defects, including autologous bone grafts (AGs), polymethyl methacrylate (PMMA) flaps, and titanium mesh (T-mesh). However, the long-term results of cranioplasty after use of these materials are controversial. METHODS: Medical records of 596 patients who underwent cranioplasty at our medical center between 2009 and 2015 with at least 2.5 years of follow-up were retrospectively reviewed. Patients were classified into 3 groups according to the materials used: AG, three-dimensional PMMA, and T-mesh. Demographic and clinical characteristics and postoperative complications were analyzed. RESULTS: Cranioplasty with AG had the highest bone flap depression rate (4.9%; P = 0.02) and was associated with a 26% long-term bone flap resorption. Younger age was a risk factor for bone flap resorption. T-mesh had a higher risk of postoperative skin erosion and bone exposure (17%; P = 0.004). Patients with diabetes, previous craniotomy, or hydrocephalus showed a higher risk of postoperative skin erosion. PMMA was associated with the highest rate of postoperative infection (14.4% <3 months, 28.1% >3 months; P < 0.05), and previous craniotomy may increase the infection risk after cranioplasty with PMMA. CONCLUSIONS: Complications after cranioplasty are high, and the various types of cranioplasty materials used are associated with different complications. Surgeons need to be aware of these potential complications and should choose the appropriate material for each individual patient.