Recombinant physical crosslinkers for collagen to improve treatment of bone fractures

• Grant number: 23/07102-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: October 20, 2023
• End date: June 19, 2024
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Ana Claudia Muniz Renno
• Grantee: Amanda de Souza
• Supervisor: Renko de Vries
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Institution abroad: Wageningen University & Research, Netherlands
• Associated to the scholarship: 21/13056-0 - 3D printing of collagen skin dressings from marine sponges and fish skin: a comparative study for application in skin wounds treatment, BP.DR

Abstract

Bone fractures lead to a large number of hospitalization and surgeries and place a significant financial burden on healthcare system. Treatments with faster and better recovery, for example through improved biomaterials, would have a large impact. A frequently used biomaterial in treating bone fractures is collagen, the main protein constituent of extracellular matrix (ECM). This material is now mostly extracted from bovine and porcine sources, but these sources have well-known problems such as risks for infections and being unacceptable for many people for ethical or religious reasons. Marine collagens, especially from sponges, do not suffer from these problems, and may be a suitable alternative. While the biological response of the materials appears to be promising, when formulated as (injectable) hydrogel, their mechanical and handling properties are not as good as collagen extracted from bovine and porcine sources. To remedy this, we propose to develop a protein that can be added in small amounts to fibrillar collagen, and which physically crosslinks the fibers, thus improving mechanical and handling properties of the collagen hydrogels. The proteins to be developed will consist of biocompatible elastin-like proteins with terminal collagen-binding peptides. The main aim of this study is to simply improve the mechanical and handling properties of sponge collagen hydrogels. However, it is becoming increasingly clear that all cells are sensitive to the mechanics of their ECM surroundings. Therefore, we will also investigate how the altered mechanical properties of the hydrogels affect the response of bone cells to the biomaterial (migration, proliferation and differentiation). In this way we expect to be able to arrive at hydrogels composed of sponge-derived fibrillar collagen with improved mechanical properties for promoting bone regeneration. (AU)