Biology subjects

Villemure, I.

Publications and source records attributed to Villemure, I..

3 recordsLinked to original sources

bioRxiv2026

3D-Printed Scaffolds for Local Chemotherapeutic Delivery in Resected Spine Metastases

Spinal metastases often occur secondary to breast, lung and prostate cancer and lead to instability, pain and poor quality of life. Standard care for spine metastases includes a multidisciplinary approach with surgery playing a major role in tumor resection, stabilization and decompression. Surgical resection with adjuvant is an effective treatment, yet it is often accompanied by tumor recurrence from residual disease. Furthermore, acrylic cements applied to defect sites provide stability, but they do not promote bone repair and can become destabilized during recurrence events. Developing new tools to stabilize defect sites, promote bone repair and locally deliver therapeutics may circumvent these limitations. We have previously developed mechanically competent 3D printed lactide/mineral scaffolds conducive to bone repair in vivo. We have also developed 3D printed nanoporous scaffolds conducive to both bone repair and chemotherapeutic delivery. Here, we set out to assess doxorubicin and cisplatin uptake and release rates and efficacy of drug delivery in 2D and custom physiological 3D cultures of two human cancer cell lines associated with metastases, MDA-MB-231 (human breast) and C42B (human prostate). Composite scaffolds had a compressive modulus close to trabecular bone, and could sustainably and effectively release doxorubicin and cisplatin as measured against both breast and prostate cell lines in 2D and 3D custom physiological metastases models. As a proof-of-concept, doxorubicin loaded composite scaffolds were implanted into rat caudal vertebrae following MDA-MB-231 xenograft resection. Following 6 weeks of implantation, no adverse events were noted and microCT analysis revealed boney integration of the construct. Taken together, these data indicate that our composite scaffolds may be an appropriate alternate therapy to stabilize bone defects, promote bone repair and effectively inhibit cancer recurrence post-tumor resection. Future work will test composite scaffolds using in vivo bone metastases models.

bioengineering↗

bioRxiv2023

Zoledronate reduces microdamage accumulation in cortical bone of ovariectomized rats

As a daily physiological mechanism in bone, microdamage accumulation dissipates energy and helps to prevent fractures. However, excessive damage accumulation might bring adverse effects to bone mechanical properties, which is especially problematic among the osteoporotic and osteopenic patients treated by bisphosphonates. Some pre-clinical studies in the literature applied forelimb loading models to produce well-controlled microdamage in cortical bone. Ovariectomized animals were also extensively studied to assimilate human conditions of estrogen-related bone loss. In the present study, we combined both experimental models to investigate microdamage accumulation in the context of osteopenia and zoledronate treatment. Three-month-old normal and ovariectomized rats treated by saline or zoledronate underwent controlled compressive loading on their right forelimb to create in vivo microdamage, which was then quantified by barium sulfate contrast-enhanced micro-CT imaging. Weekly in vivo micro-CT scans were taken to evaluate bone (re)modeling and to capture microstructural changes over time. After sacrifice, three-point-bending tests were performed to assess bone mechanical properties. Results show that the zoledronate treatment can reduce cortical microdamage accumulation in ovariectomized rats, which might be explained by the enhancement of several bone structural properties such as ultimate force, yield force, cortical bone area and volume. The rats showed increased bone formation volume and surface after the generation of microdamage, especially for the normal and the ovariectomized groups. Woven bone formation was also observed in loaded ulnae, which was most significant in ovariectomized rats. Although all the rats showed strong correlations between periosteal bone formation and microdamage accumulation, the correlation levels were lower for the zoledronate-treated groups, potentially because of their lower levels of microdamage. The present study provides insights to further investigations of pharmaceutical treatments for osteoporosis and osteopenia. The same experimental concept can be applied in future studies on microdamage and drug testing.

bioengineering↗

bioRxiv2021

Air leaks: stapling affects porcine lungs biomechanics

During thoracic operations, surgical staplers resect cancerous tumors and seal the spared lung. However, post-operative air leaks are undesirable clinical consequences: staple legs wound lung tissue. Subsequent to this trauma, air leaks from lung tissue into the pleural space. This affects the lungs physiology and patients recovery. The objective is to biomechanically and visually characterize porcine lung tissue with and without staples in order to gain knowledge on air leakage following pulmonary resection. Therefore, a syringe pump filled with air inflates and deflates eleven porcine lungs cyclically without exceeding 10 cmH2O of pressure. Cameras capture stereo-images of the deformed lung surface at regular intervals while a microcontroller simultaneously records the alveolar pressure and the volume of air pumped. The raw images are then used to compute tri-dimensional displacements and strains with the Digital Image Correlation method (DIC). Air bubbles originated at staple holes of inner row from exposed porcine lung tissue due to torn pleural on costal surface. Compared during inflation, left upper or lower lobe resections have similar compliance (slope of the pressure vs volume curve), which are 9% lower than healthy lung compliance. However, lower lobes statistically burst at lower pressures than upper lobes (p-value<0.046) in ex vivo conditions confirming previous clinical in vivo studies. In parallel, the lung deformed mostly in the vicinity of staple holes and presented maximum shear strain near the observed leak location. To conclude, a novel technique DIC provided concrete evidence of the post-operative air leaks biomechanics. Further studies could investigate causal relationships between the mechanical parameters and the development of an air leak.

physiology↗