UNICoRN-UNderstanding the biological mechanism of combined BMP-cell based Implants for bone regeneration in a Clinically RelevaNt microenvironment.

Neurofibromatosis type 1 (NF1) is a congenital disease caused by loss-of-function mutations in NF1 gene. Patients with NF1 can develop serious skeletal disorders, which is characteristic as non-healing tibia fracture. Current orthopaedic treatment for NF1 patients remains challenging, which strongly urges clinicians and researchers to explore alternative treatments. Recently, tissue engineering (TE) has emerged as a promising approach to treat NF1-associated non-healing fracture. A concept for this approach is to generate a TE construct by combining osteogenic progenitor cells and osteoinductive biomolecules on optimal carrier materials, which can be implanted in vivo, and act as a robust engine with a bone formation capacity which is able to functionally heal a diseased defect area.Periosteum-derived cells (PDC) and bone morphogenetic protein (BMP) represent promising ‘raw materials’ as osteogenic cells and osteoinductive biomolecules, respectively. However, extremely limited information is available about the biological functions of combined BMP-cell based implants in NF1-associated skeletal defects. Consequently, this proposal is aimed to explore biological performance and underlying mechanism of a combined BMP-cell constructs for bone regeneration in a clinically relevant NF1 microenvironment. This research will form solid scientific evidence to translate TE concept to treat skeletal disorders in NF1 patients, which is a first step towards personalized medicine.