Determination of tumor tissue mechanical properties, toward quantification of implication of tumor in whole bone resistance: a preliminary study

Benjamin Delpuech (1) , Stéphane Nicolle (1) , Cyrille Confavreux (2) , Lamia Bouazza (2) , Sandra Geraci (2) , Philippe E Clézardin (2) , David Mitton (1) , Hélène Follet (2)

1 LBMC UMR T9406 - Laboratoire de Biomécanique et Mécanique des Chocs
2 LYOS - Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases

Introduction Metastatic cancer affects the skeleton [1]. Bone metastases weaken bones, and physicians have to decide the emergency of a surgical intervention. Yet the tools at their disposal do not allow the accurate prediction of metastatic bone failure. Past studies showed that patient-specific finite element analysis (FEA) could contribute to improve this diagnosis. However, in those studies, bone metastases were not taken into account while experimental test showed that they could have an impact on whole bone resistance [2]. Therefore, our aim is to quantify bone tumor mechanical properties, in order to be able to determine the influence of tumor on the whole bone resistance, using FEA. Methods Two BALB/c nude mice were subcutaneously injected with human breast cancer cells (lytic lesions). Resulting tumors were cut into 10 samples and their shear modulus (G*) was assessed by small amplitude oscillatory shear tests between 0.1 to 10,000Hz. For further comparison, samples of muscles (2), skin (4) and fat (1) of the same mice were dissected and tested following the same protocol. Simultaneously, two different mice were intra-tibialy injected (right limb: tumor cells, left limb: phosphate buffered saline). After sacrifice and µCT imaging (10µm resolution), the tibias were compressed with a pre-cycling (30 cycles between -0.5N and -2N at 0.5Hz) and until failure in quasi-static test (displacement 0.03mm/s). Tibia base was embedded while a mold of the tibial plateau was performed to spread the loading. These tests allowed the characterization of stiffness and ultimate load of each limb. Results Rheological tests showed that tumor shear modulus was 90% higher than the one of fat and 50% higher than those of muscles and skin. On the other hand, the tibia tests in compression showed the tumoral limb has an ultimate load and a stiffness of respectively 33% and 25% lower than the contro-lateral limb. Discussion & Perspectives Our first results show that the tumor has a non-negligible shear modulus and is even greatly higher than the one of the other soft tissues tested. The results showed also that the tumor has an effect on both bone stiffness and strength. The next step is to replicate by FEA simulation the experimental tests in compression on tibia. The tibia model will be based on the µCT acquisition done prior to mechanical test. In addition to the mechanical properties of bone (grey scale) the mechanical properties of the tumor tissue (from rheological tests) will be and not taken into account in order to quantify the implication of tumor on whole bone strength. Acknowledgements This work is supported by LabEx PRIMES (ANR-11-LABX-0063). References [1] “Coleman RE. Cancer 1997,pp.1588–94.” [2] “Derikx et al. J of Biomechanics. 2015, pp.761-6”

Domaines: Biomécanique [physics.med-ph]

Benjamin Delpuech, Stéphane Nicolle, Cyrille Confavreux, Lamia Bouazza, Sandra Geraci, et al.. Determination of tumor tissue mechanical properties, toward quantification of implication of tumor in whole bone resistance: a preliminary study. 8th World Congress of Biomechanics, Jul 2018, Dublin, Ireland. ⟨hal-02086220⟩