Development of organic-inorganic innovative scaffolds for bone tissue engineering based on polymer honeycomb membrane and bioactive glass-based mineral phase

Audrey Deraine

    Research output: Book/ReportDoctoral thesisCollection of Articles

    Abstract

    When a significant bone defect develops as a result of trauma, bone resection owing to malignancy or infection, or both, bone needs aid from a substitute to regenerate while preventing the invasion of fibrous tissue into the defect. To prevent the implant site invasion by fibrous tissue, barrier membranes have been fabricated from naturally sourced or synthetic polymers. One characteristic of major importance, to consider in the fabrication of a barrier membrane, is its porosity. The pores in the membrane should allow appropriate nutrient and waste flow while preventing the cells from entering the defect. However, the currently available membranes degrades faster than the bone regeneration occurs. To overcome this challenge, focused has been made on materials able to accelerate bone regeneration in order to close the gap between the membrane degradation and the bone regeneration rate. For this purpose, one strategy is to use bone graft in combination with a barrier membrane, although it implies a two-step procedure with two distinct materials which can be challenging for surgeons. As bone graft, bioactive glasses (BG) have made a breakthrough the past decade since they are able to degrade, bond to bone, and induce osteogenesis. Materials for bone graft should have suitable porosity to allow the neo formed bone to colonize the structure and eventually replace it. Processing BG into 3D porous scaffolds has revealed to be challenging but not impossible.

    This thesis project has been designed with the aim to propose a new biphasic material that would avoid the fibrous tissue in-growth and the two-steps surgical procedure by directly linking the graft and the barrier membrane.1) The membrane, made of poly-L-co-D, L-lactic acid (PLDLA), was created at the surface of the materials by the Breath Figure Method (BFM) to give it a honeycomb-like porous structure, in order to prevent cell migration while maintaining nutrients migration and waste removal.

    2) The membrane was generated on chosen BG, namely the S53P4, also known as BoneAlive® S53P4, and the 13-93B20, an experimental BG composition containing boron (B), or a decellularized bone matrix (DBM) to support bone regeneration.

    The impact of BG surface chemistry on membrane adhesion has been studied and revealed that, the conditioning of the BGs induces calcium phosphate (CaP) precipitation at their surface which results in a stronger attachment of the membrane.

    Successively, our assemblies were sterilized through gamma irradiation and, although irradiation induced some changes in physicochemical properties of both the polymer and BG, cell-material interactions were found unaffected.

    Finally, a 3D printed 13-93B20 scaffold was specifically designed to generate the honeycomb PLDLA membrane at its surface. After immersion in simulated body fluid (SBF), the assemblies were found to be able to precipitate hydroxyapatite (HA). When put in contact with osteoblast-like cell, the assemblies were found to support cell adhesion and growth while providing an effective way of segregating osteoblasts-like cells and fibroblasts thanks to the honeycomb membrane.

    In summary, a new biphasic scaffold based on an inorganic and an organic phase directly linked together was successfully developed. The material showed a great cohesiveness during the immersion and revealed itself to be able to support hydroxyapatite precipitation. Furthermore, it showed great capacity to support cell adhesion, growth and proliferation while providing an effective space delimitation for osteogenic and fibroblastic cells.

    This scaffold paves the way toward new devices allowing space separation and cells segregation in order to improve bone regeneration while avoiding the deleterious fibrous tissue ingrowth.
    Original languageEnglish
    Place of PublicationTampere
    ISBN (Electronic)978-952-03-3230-3
    Publication statusPublished - 2023
    Publication typeG5 Doctoral dissertation (articles)

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