Bone regeneration: Biomimetic nanocarriers from cell membranes to delivery lncRNA

• Grant number: 22/14409-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2024
• Status: Discontinued
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Willian Fernando Zambuzzi
• Grantee: Amanda Fantini de Camargo Andrade
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated scholarship(s): 24/23670-6 - Development of a multifunctional lncMALAT1-activated collagen-nanohydroxyapatatite scaffold to enhance the repair of large critical sized bone defects., BE.EP.DR

Abstract

One must consider the central role that the skeleton plays in the human body, following the command that other tissues and organs regulate, which indicates that, in addition to its mechanical functions, bone is an endocrine tissue, which modulates cellular activities in different fabrics. The growing understanding that bone is a paracrine and endocrine organ serves to broaden our understanding of aspects involved in metabolic disorders and degenerative diseases, as well as may help in the development of new strategies within treatment programs. For this, understanding the metabolism and functions of the specialized cells that make up the bone tissue is fundamental. For this, understanding the metabolism and functions of the specialized cells that make up the bone tissue is fundamental. In this context, although a connection between osteoblasts and endothelial cells has been demonstrated, the relevance of vascular smooth muscle cells (VSMCs) and endothelial cells (HUVEC) in this scenario is little known. The results showed that both endothelial cells and VSMCs release extracellular surfaces (EVs), exosomes (120 nm), which alter the function and metabolism of osteoblasts, however, little is known about another type of EVs, microvesicles , which are also released by these cells and can interfere with osteomodulation. Currently, nanocompounds are designed to increase the activity of key cellular effector switches by altering their metabolism. Thus, the present study aims to develop a nanocarrier for the transport of osteogenic molecules to bone tissue cells. With this proposal, modified hydroxyapatite nanoparticles (HA-NP-APTES-HOTTIP) will be synthesized from the main constituents of biomembranes of VSMCs and HUVEV, in order to direct the action of hydroxyapatite and osteogenic molecules, such as lcn-HOTTIP. Initially, the preparation of the nanocarriers loaded with HA-NP-lncRNA will be carried out, followed by the reconstitution of the nanocarriers with membrane fragments from VSMCs and HUVEC, a stage in which it will be carried out in collaboration with the group led by Prof. Valtencir Zucolotto (Physics Institute of São Carlos-USP).The nanocarrier will be tested for: a) toxicity; b) internalization by hMSCs; c) performance in classic mechanisms of survival, proliferation and cell differentiation in vitro. With the aim of seeking advances in the area of biotechnology, the main motivation of the project is related to the continuity of a study previously carried out by our research group. Thus, this new research project consists of giving continuity and applicability to the study of previously developed nanovesicles. As expected, results we aim to promote the interaction of these nanocarriers with mesenchymal stem cells in order to stimulate an osteogenic profile. Considering these advances already achieved, this project proposes translational research applying the knowledge accumulated in this field in a biotechnological platform, mainly focusing on the biomanufacture of nanoparticles from biomembranes of VSMCs and HUVEC as a vehicle for delivery of osteogenic components.