Engineering of a biomimetic, hierarchically structured bone substitute based on a hybrid composite scaffold containing human bone particles

摘要

Introduction: Over the last few years, the focus of bone engineering has shifted towards the development of biomimetic scaffolds. The ability of a scaffold to succeed as a template for cells depends on its potential to provide an appropriate microenvironment and to mimic the bone structure. In this regard, engineering trabecular-like, three-dimensional bone tissue throughout biodegradable biopolymer scaffolds is a significant challenge. Herein, we have proposed an innovative hybrid platform based on a silica-gelatin sol-gel system. The idea is to combine mesoporous silica mesh and gelatin gel to mimic the structure and the biological properties of a native extracellular matrix made of collagen network and glycosaminoglycan gel. Osteoconduction will be promoted with microparticles of human bone @biobank. Figure 1: Schematics representing the processing for synthetize the 3 D scaffold hybrid Materials and Methods: The material is made as follows. First, a solution made of gelatin and bone particles is prepared. A bi-functional crosslinker - glycidylsiloxane-GPTMS is added to the solution, which leads to the activation of all organic species (the gelatin molecules, and probably, the collagen part of the bone elements as well). At the same time, a mineral sol, made of silica precursors -TEOS- is prepared in presence of a specific surfactant -CTAC-. The concentration used with the surfactant, above the critical micelle concentration, result in specific mesoporous structure that ultimately defines one the mesoporosity in the engineered materiapl. Finally, both -organic / inorganic- phases are mixed together in order to generate the composite material. Results and Discussion: These hybrid scaffolds exhibit covalently linked interpenetrating networks of organic and inorganic components, which allow decoupling mechanical properties and degradation properties. The various steps and the nature of the different reactions involved in the fabrication of the scaffolds such as chemical cross-linking and foaming, are essential to tune the multiple structural, mechanical and biological properties. Figure 2: Schematics representing the structuring of inorganic and organic networks in the hybrid In a first attempt foaming process was investigated. Preliminary results demonstrate the proof of concept to generate hierarchically structured materials presenting pores ranging from 1 nm to few microns and specific area superior to 1000m~2/g. Moreover, they present interesting mechanical properties. Silica-gelatin-based materials enriched with bone particles appear as promising candidates for bone tissue engineering.