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Novel Capsosome-Based Approach to Promote Angiogenesis for Bone Repair

Final Report Summary - BONE CAPSOSOME (Novel Capsosome-Based Approach to Promote Angiogenesis for Bone Repair)

The main aim of BONE CAPSOSOME project is to develop smart polymer carriers containing liposomal compartments (capsosomes) as a novel platform of delivery system that enables controlled time release of multiple encapsulated biomolecules to promote angiogenesis for bone repair.

The specific objectives for the project BONE CAPSOSOME are as follows:
1. To assemble polymer carriers with liposomal compartments (capsosomes) that enable encapsulation and controlled release of biomolecules
2. To design cell co-culture systems and incorporate the cargo-loaded carriers into the cell matrix
3. To assess cell viability and proliferation on the materials
4. To assess the ability of the materials towards promoting angiogenesis

Over the entire period of my Marie Curie Fellowship (24 months), there has been significant and excellent progress towards achieving the objectives of this project, in particular in material assembly and characterizations; cell-material interfaces; and controlled release of biomolecules. Initially, the project proposed the use of hollow polymeric capsules to confine multiple liposomal subcompartments, however we found that polymer fiber scaffolds produced by electrospinning technique are much more advantageous for the proposed concept because: a) polymer fibers have higher surface areas to enable encapsulation of higher amounts of cargo-loaded liposomes; b) their orientation and mechanical properties can be finely tuned to affect biological behaviour at cell-material interfaces; and c) they serve as biomimetic cell niche. The judicious choice of the polymeric system is indeed an improvement for the development of this project and there is no impact on available resources and planning. The first polymer fibers containing intact liposomal compartments obtained from blend electrospinning were reported. The polymer/liposome assembly was characterized and optimized, and the mechanical properties of these fibers were explored. Encapsulation and controlled release of cargo via temperature trigger were successfully demonstrated. In addition, both polymer/liposome fibers and the encapsulated cargo were found to have excellent stability at physiological conditions; importantly, the use of liposomes as cargo reservoirs preserved the bioactivity of the encapsulated proteins, which is one of the crucial aspects in successful delivery of growth factors. The interaction of the polymer/liposome fibers with biological systems (in vitro studies) was investigated. They were proved to be biocompatible and allowed cell adhesion. Furthermore, the presence of the liposomal compartments within the polymer fibers promoted cell proliferation. Interesting results highlighting the functionality and impact of the polymer/liposome assembly include successful controlled release of nitric oxide to promote angiogenesis, achieved via substrate mediated enzyme prodrug therapy, which allows interactive control of amount and rate of biomolecules delivered. The results obtained during the development of this project present significant advances in the field of material chemistry, therapeutic delivery, and regenerative medicine. Overall, the critical objectives outlined in the proposal were achieved and the tasks were in line with the proposed schedule. The project was successfully executed, demonstrating novel approach to promote angiogenesis, which will lead to rapid growth of new capillary blood vessels within the scaffold construct to supply tissues with nutrients. This project addresses an important clinical challenge, and the significance and results obtained during the execution of this project will have significant impact on Europe both scientifically and economically.