Development of bio-scaffolds containing extracellular matrix vesicles by 3D printing: an innovative approach in bone regeneration

Abstract

Despite the remarkable regenerative capacity of bone, pathological conditions and critical-sized injuries can hinder its efficient repair. In this context, bone tissue engineering has emerged as a crucial research area in regenerative medicine. Recently, extracellular matrix vesicles (MVs), utilized as a cell-free therapy, have emerged as a promising strategy for regenerative medicine. However, the administration of MVs in their free form is challenging due to rapid clearance by the body. Thus, this project proposes the production and characterization of three-dimensional scaffolds based on biopolymers and collagen, incorporated with MVs, aiming for their innovative application in bone tissue regeneration. The scaffold design will seek to mimic the microenvironment of the bone extracellular matrix, promoting cell recognition, proliferation, and differentiation. To enhance the rheological properties of collagen gels, enabling 3D printing, hydrogels containing blends with starch and carrageenans will be developed. MVs will be isolated from MC3T3 pre-osteoblasts, characterized in relation to their physicochemical properties and mineralization capacity, and incorporated into the hydrogels. Scaffold production will occur through 3D printing by extrusion, aiming to obtain materials with mechanical properties similar to trabecular bone, controlled porosity, and customization to the size and shape of the defects. This project will expand the use of starch in the production of personalized biomaterials when added to collagen and modified with MVs and also represents an innovative approach to bone regeneration through the use of biopolymers, obtained from renewable sources. Furthermore, carrageenans have a structure that resembles chondroitin sulfate, an important component of the bone extracellular matrix, and have superior rheological properties, allowing the production of hydrogels. The proposed methodology will include in vitro evaluations, aiming for a comprehensive understanding of the osseoinductive potential of scaffolds through the differentiation of mesenchymal cell cultures extracted from mouse bone marrow. It is anticipated that the results of this proposal will contribute to an effective and promising alternative for bone tissue regeneration, along with potential patent value and substantial benefits to human health. (AU)