When a critical-sized bone defect develops as the result of trauma, bone resection owing to malignancy or infection, or both, needs to be helped by a regenerative substitute. However, the infiltration of the defect by fibrous tissue has been shown to prevent or suppress bone regeneration. To prevent the implant site from being invaded by fibrous tissue, barrier membranes have been fabricated from naturally sourced or synthetic polymers.
“When developing a barrier membrane, control over porosity is of paramount importance. The pores in the membrane should allow an appropriate nutrient and waste flow while preventing the cells from entering the defect. However, the currently available membranes degrade faster than the bone regeneration occurs,” Audrey Deraine Coquen says.
To overcome this challenge, development has focused on materials that are able to accelerate bone regeneration to close the gap between membrane degradation and the rate of bone regeneration. For this purpose, one strategy is to use a bone graft in combination with a barrier membrane. Such strategy requires a two-step procedure with two distinct materials, which can be challenging for surgeons.
Deraine Coquen’s dissertation project was designed with the aim to propose a new biphasic material which would avoid fibrous tissue ingrowth and a two-step surgical procedure by directly linking the graft and the barrier membrane.
Firstly, a membrane – made of poly-L-co-D, L-lactic acid (PLDLA) –was created at the surface of the materials using the breath figure method (BFM), which led to a honeycomb-like porous structure to prevent cell migration while maintaining the flow of nutrients and waste removal. Secondly, the membrane was generated on a chosen bioactive glass, the S53P4, also known as BoneAlive® S53P4, and the 13-93B20, an experimental BG composition containing boron (B), or a decellularised bone matrix (DBM) to support bone regeneration.
The impact of BG surface chemistry on the membrane adhesion was studied. The results indicate that conditioning the bioactive glasses in simulated body fluid before the membrane deposition led to the precipitation of hydroxyapatite. The precipitated hydroxyapatite was found to have more affinity with the polymer membrane, leading to a stronger membrane attachment on the bioactive glass surface.
As the aim was to propose a biomedical device to be implanted, the impact of sterilisation by gamma radiation on the material properties and the interaction between the biphasic implant and cells were assessed. Gamma radiation was found to create defects in the inorganic matrix and to partially degrade the polymer membrane. However, such modification did not lead to a significant change in the cell-material interactions, confirming that gamma radiation is effective and safe in sterilising the newly developed assembly.
Finally, a 3D printed 13-93B20 scaffold was specifically designed to generate the honeycomb PLDLA membrane at its surface. When brought to contact with bone-like cells, the assemblies were found to support cell adhesion and growth. Fibroblasts (cells responsible for the fabrication of scar tissue) were plated at the surface of the membrane to demonstrate the ability of the membrane to prevent the migration of fibroblasts within the scaffolds.
“In the study, a new biphasic scaffold based on an inorganic and an organic phase directly linked together was successfully developed. The material showed great cohesiveness during the immersion and turned out to support hydroxyapatite precipitation, the first sign of bioactivity. Furthermore, the assembly showed great capacity to support cell adhesion, growth and proliferation while providing an effective space delimitation for bone-like and fibroblastic cells,” Deraine Coquen explains.
This scaffold paves the way for new devices that allow space separation and the segregation of cells to improve bone regeneration while avoiding the deleterious ingrowth of fibrous tissue.
Public defence on Wednesday 13 December
The doctoral dissertation of M.Sc. Audrey Deraine Coquen in the field of biomedical science and engineering titled Development of organic-inorganic innovative scaffolds for bone tissue engineering based on polymer honeycomb membrane and bioactive glass-based mineral phase will be publicly examined at the Faculty of Sciences at CY Cergy Paris Université at 14.30 on 13 December 2023. The venue is the Auditorium of Maison Internationale de la Recherche (address: 1 Rue Descartes 95000 Neuville-sur-Oise, France). The Opponent will be Professor Didier Lutomski from Sorbonne Université, France. The Custos will be Professor Jonathan Massera from Tampere University.