Optimization and standardization of the manufacture of an extracellular matrix mimetic hydrogel for applications in regenerative medicine, tissue engineering and other in vitro studies

• Grant number: 18/15450-5
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: March 01, 2019
• End date: November 30, 2019
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Gabriel Romero Liguori
• Grantee: Gabriel Romero Liguori
• Company: Tissuelabs Pesquisa e Desenvolvimento Ltda
• CNAE: Pesquisa e desenvolvimento experimental em ciências físicas e naturais
• City: São Paulo
• Associated research grant(s): 19/22468-0 - Characterization of extracellular matrix mimetic hydrogels derived from multiple tissues and their influence on cell behavior, AP.PIPE
• Associated scholarship(s): 19/07388-0 - Optimization and standardization of the manufacture of an extracellular matrix mimetic hydrogel for applications in Regenerative Medicine, Tissue Engineering and other in vitro studies, BP.PIPE

Abstract

The development of hydrogels for application in regenerative medicine, tissue engineering and in vitro studies that require three-dimensional cell culture has been the focus of intense investment by universities and companies around the world. These hydrogels seek to mimic features of the extracellular matrix environment, such as biochemical clues and biomechanical stimuli. Taking into account the importance of the components of the extracellular matrix of each specific type of tissue, hydrogels derived from decellularized extracellular matrix began to be used with the proposal to provide the cells with a set of properties and signs of the native microenvironment, structurally and biologically, capable of interact as the matrix itself, supporting and guiding cell adhesion, proliferation and differentiation. However, the current process for manufacturing such hydrogels is completely manual and scaled-down, consuming proportionally many resources - both material and human - and presenting considerable variations between batches. In order to transform these hydrogels into a commercial product that can be used by any researcher interested in performing three-dimensional cell culture, this process needs to be optimized in order to overcome these two major technical-scientific challenges: the reproduction of the process on a large scale and the standardization of the fabrication methods. The primary objective of this project is the optimization and standardization of the process of manufacturing a hydrogel derived from decellularized extracellular matrix, through the mechanization of the decellularization and gelation processes, as well as the introduction of refinement processes. For this, two bioreactors will be made, one for the decellularization process and one for the gelation process, and a hydrogel purification protocol will be developed. Secondary and consequently to this, we aim to evaluate the biochemical and biomechanical properties of this hydrogel and its ability to support three-dimensional cell culture. In summary, the present project aims to evaluate the technical-scientific feasibility of the manufacture of a decellularized extracellular matrix hydrogel for three-dimensional cellular culture on an industrial scale. (AU)