A Computational Model for Fracture Healing Integrated with Mechanical Stimulation and Growth Factors
Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Non-union bone fractures are a standing problem for clinical treatments. It has been found that the exogenous growth factor recombinant human bone morphogenetic protein-2 (rhBMP-2) induces bone healing in potential non-union fractures. However, the currently used clinical dose of rhBMP-2 is high and causes side-effects. Mechanical loading is known to enhance the induced effects of rhBMP-2 in bone healing, which may lead to a reduced required dose. Yet, the exact underlying mechanism is unknown.
To further investigate the combined role of mechanical loading and rhBMP-2 in the early phase of fracture healing a 2D computational model was developed. The model uses a lattice-based approach where biological rule-based events are combined with finite element analysis to simulate both untreated bone healing progression and when subjected to mechanical loading and rhBMP-2. Two healing cases were investigated: normal fracture healing in a small bone defect (1 mm gap) and non-union fracture healing in a large bone defect (5 mm gap). By varying the magnitude and timing of applied load as well as the rhBMP-2 dose, a combination that would reduce the currently used rhBMP-2 dose and still enable healing in a large bone defect was searched.
The model could simulate fracture healing in a large bone defect when subjected to rhBMP-2, independently of the applied load. Also the expected non-union result in a large bone defect without applied rhBMP-2 was obtained. The model could not capture normal fracture healing in a small bone defect as well as bone remodelling.
It was found that a 50 % reduced rhBMP-2 dose could not induce healing in a large bone defect when applied separately but when applied together with load. Additionally, this combination of stimulation gave similar results compared to other combinations using higher rhBMP-2 doses.
To conclude, even though the model was able to replicate some of the healing events seen experimentally, it is in need of modifications to correct current deficiencies. Still, after some further development and validation, the model has the potential to be used in future studies of fracture healing when influenced by mechanical loading and rhBMP-2. The found possibility for a reduced dosage of rhBMP-2 when applied together with load has to be further investigated before any conclusions can be drawn.
Place, publisher, year, edition, pages
2014. , 91 p.
Computational modelling; Non-union bone fracture; Fracture healing; Growth factors; BMP-2; rhBMP-2; Mechanical loading; FEM
IdentifiersURN: urn:nbn:se:kth:diva-143536OAI: oai:DiVA.org:kth-143536DiVA: diva2:707469
Subject / course
Master of Science in Engineering - Medical Engineering
Giordano, Chiara, Doctoral student
Kleiven, Svein, Associate Prof./Sr. lecturer