RESUMO
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.
Assuntos
Bioimpressão , Impressão Tridimensional , Veias Pulmonares , Sirolimo , Sirolimo/farmacologia , Sirolimo/administração & dosagem , Bioimpressão/métodos , Humanos , Constrição Patológica , Células Endoteliais/metabolismo , Células Endoteliais/efeitos dos fármacos , Nanopartículas de Magnetita , Técnicas In Vitro , Sistemas de Liberação de Medicamentos/métodos , Proliferação de Células/efeitos dos fármacosRESUMO
CONTEXT: Pancreatic pseudocysts are relatively common complications of pancreatitis. A pseudocyst can result from an episode of acute pancreatitis, exacerbation of chronic pancreatitis, or trauma. Treatment is indicated for persistent, symptomatic pseudocysts and in the case of related complications. CASE REPORT: We describe the case of a 66-year-old man who referred to our department for bowel obstruction caused by a necrotic pancreatic bezoar occurring 16 days after the patient underwent a jejunal-pseudocyst anastomosis performed to treat a post-pancreatitis voluminous pseudocyst obstructing the gastric outlet. CONCLUSION: In case of intestinal obstruction after a jejunal-pseudocyst anastomosis, pancreatic bezoar should be considered in the armamentarium of the differential diagnosis.
