Targeted Rapamycin Delivery via Magnetic Nanoparticles to Address Stenosis in a 3D Bioprinted in Vitro Model of Pulmonary Veins.

Vascular cell overgrowth and lumen size reduction in pulmonary vein stenosis (PVS) can result in elevated PV pressure, pulmonary hypertension, cardiac failure, and death. Administration of chemotherapies such as rapamycin have shown promise by inhibiting the vascular cell proliferation; yet clinical success is limited due to complications such as restenosis and off-target effects. The lack of in vitro models to recapitulate the complex pathophysiology of PVS has hindered the identification of disease mechanisms and therapies. This study integrated 3D bioprinting, functional nanoparticles, and perfusion bioreactors to develop a novel in vitro model of PVS. Bioprinted bifurcated PV constructs are seeded with endothelial cells (ECs) and perfused, demonstrating the formation of a uniform and viable endothelium. Computational modeling identified the bifurcation point at high risk of EC overgrowth. Application of an external magnetic field enabled targeting of the rapamycin-loaded superparamagnetic iron oxide nanoparticles at the bifurcation site, leading to a significant reduction in EC proliferation with no adverse side effects. These results establish a 3D bioprinted in vitro model to study PV homeostasis and diseases, offering the potential for increased throughput, tunability, and patient specificity, to test new or more effective therapies for PVS and other vascular diseases.

Donor- and recipient-site morbidity of vascularized fibular and iliac flaps for mandibular reconstruction: A systematic review and meta-analysis.

The aim of this article is to evaluate the early and late morbidities of the donor- and recipient-site in patients undergoing mandibular reconstruction using either vascularized fibular flap (VFF) or vascularized iliac flap (VIF). Electronic databases, including PubMed, Web of Science, Cochrane Central and Embase, were explored for literature published until October 2020. A total of twenty-four articles reporting complications following mandibular reconstruction surgery with follow-up periods ranging from six to 63 months were selected based on the exclusion criteria. For each research, the JBI Critical Assessment Tool and the ROBINS-I Tool were used to analyze the methodological quality and the risk of bias. A single-arm meta-analysis was performed to have a synthesized analysis of the donor- and recipient-site early and late morbidities. Results showed that the early morbidities in VFF group ranged from 3% to 12%, and the late morbidities in VFF group ranged from 5% to 67%. In VIF group, the early morbidities ranged from 3% to 16%, and the donor-site late morbidities ranged from 6% to 43%. Complications with the top three morbidities in the VFF group were: chronic sensory disturbances at the donor-site (67%), malocclusion (22%) and chronic lower limb weakness (20%); and in the VIF group were: chronic sensory disturbances at the donor-site (43%), chronic pain at the donor-site (26%), chronic gait disturbance (20%). Further controlled clinical trials are needed to assess the long-term outcome of VFF or VIF grafting.