Tecnologias para estudo e tratamento da insuficiência venosa crônica: desenvolvimento de microambientes e abordagens nanotecnológicas

Abstract

Venous insufficiency is a disease caused by valvular incompetence and is highly prevalent in Western countries, significantly burdening health systems. The most severe form of the disease consists of venous ulcers that are difficult to heal. In view of this, the main objective of this thesis was to develop biomaterials for the study and treatment of venous ulcers, through nanotechnological approaches and regenerative medicine. In order to do so, three-dimensional microenvironments (3D) were developed in order to investigate the response of stem cells to different mechanical properties of the extracellular matrix, as well as the expression of proteins released from nanoparticles containing messenger RNA (mRNA) in order to propose a model of pathology study. In addition, compression stockings containing nanoencapsulated hesperetin has been developed for the treatment of venous ulcers. In view of the above, 720 hydrogels of different mechanical properties (9 to 46 kPa) were printed as biomechanical platforms of the extracellular matrix. The response of stem cells to these matrices was directly related to stiffness of the microenvironment, without damage to cellular viability. In addition, stiffer matrices presented a greater expression of proteins, which contributes to new studies involving the biochemical factors present in the microenvironment of the venous disease. Compressive stockings containing nanoencapsulated hesperetin have been shown to be promising for the treatment of ulcers by controlled release of hesperetin from the textiles into the microenvironment of the lesions. These nanocapsules remained adhesive in the textile during five washes, which makes this biomaterial interesting to treat this disease, since it associates the effect of the compression to the hypotensive activity of the hesperetin in the vascular endothelium. In view of this, we present the case report of a patient with long unhealed venous ulcers for two years, with the therapies prescribed before the beginning of this study. After six months of treatment with these compressive stockings, the patient presented significant improvement in their quality of life, associated with the disappearance of pain associated with injury and excellent healing. In addition, a significant whitening of the perilesional area was observed due to reduction of melanin and erythema. The healing of the lesions also contributed to the reduction of the venous diameters of different segments of the saphenous vein. Together, these results contribute to the desired clinical outcomes in the treatment of venous ulcers and contribute to further studies with larger samples. This research therefore contributes to the emergence of new therapeutic options for a disease of such importance in the context of public health, which is an essential part of Health Policies and economic development.