Liposome-based coatings for immune stimulation and bone regeneration
Prof. Dr. E. Mastrobattista1), University Utrecht/The Netherlands
Ms Fatemeh Jahanmard (PhD fellow sponsored by the PRC) - Utrecht University, Utrecht, The Netherlands (email@example.com)
This project aims to lay the foundation for the use of liposomes to stimulate bone regeneration (osteogenesis) by means of mild immune activation. This is nourished by the knowledge that a short-lived inflammation is pivotal for normal bone healing after damage, and by recent findings that local induction of a mild inflammation can lead to de novo bone formation. Factors such as liposome charge and type of phospholipid will be addressed regarding their intrinsic immuno-stimulatory and osteogenic effects. Furthermore, the functionalization of liposomes with antagonists for pattern-recognition-receptors (PRRs), which could enhance their inflammatory activity, will be investigated. PRR modulation has led to clinical efficacy in anticancer drugs or vaccines. However, the usage for musculoskeletal disease is still in its infancy, and it is unknown which PRR ligands have greatest osteogenic potential.
In addition, it is unclear how (functionalized) liposomes must be applied at the biomaterial-tissue interface. At the practical level, the demonstration of the feasibility of liposome-stimulated osteogenesis by fabricating a liposome-based implant coating is aimed. It is hypothesized that forming a stable bone-inductive liposome film on the implant would maximize the local effects and minimize systemic effects of liposomes. In the future, this approach can be expanded to create multifunctional implant coatings and further enhance the survival of various implantable devices utilized in orthopedic and trauma patients. Although the current study will focus on the immunomodulatory and regenerative properties of liposomes for bone regeneration, the same principle can potentially be applied to medical devices to restore heart, nerve of muscle tissues, thus comprising an enormous patient population. In an ideal scenario, orthopedic implants provide de novo bone formation by recapitulating the mild inflammation needed for physiological bone regeneration.
Benefit for the community
The current efforts are aimed at expanding the use of liposomes beyond the field of inflammatory disease and oncology, and to address the current limitations seen in musculoskeletal tissue repair. The concept of forming a stable liposome surface layer method can be applied to various trauma and orthopedic implants to improve bone ingrowth and/or bone integration. A large patient population could benefit from such an approach, the most obvious applications are: prostheses, degradable bone substitutes, and smart fixation devices for fractures.