Giuseppe Falvo D'Urso Labate

Mathematical modeling of intraperitoneal drug delivery: simulation of drug distribution in a single tumor nodule

Abstract The intraperitoneal (IP) administration of chemotherapy is an alternative treatment for peritoneal carcinomatosis, allowing for higher intratumor concentrations of the cytotoxic agent compared to intravenous administration. Nevertheless, drug penetration depths are still limited to a few millimeters. It is thus necessary to better understand the limiting factors behind this poor penetration in order to improve IP chemotherapy delivery. By developing a three-dimensional computational fluid dynamics (CFD) model for drug penetration in a tumor nodule, we investigated the impact of a number of key parameters on the drug transport and penetration depth during IP chemotherapy. Overall, smaller tumors showed better penetration than larger ones, which could be attributed to the lower IFP in smaller tumors. Furthermore, the model demonstrated large improvements in penetration depth by subjecting the tumor nodules to vascular normalization therapy, and illustrated the importance of the drug that is used for therapy. Explicitly modeling the necrotic core had a limited effect on the simulated penetration. Similarly, the penetration depth remained virtually constant when the Darcy permeability of the tissue changed. Our findings illustrate that the developed parametrical CFD model is a powerful tool providing more insight in the drug transport and penetration during IP chemotherapy.

Bone structural similarity score: a multiparametric tool to match properties of biomimetic bone substitutes with their target tissues

Background One of the hardest tasks in developing or selecting grafts for bone substitution surgery or tissue engineering is to match the structural and mechanical properties of tissue at the recipient site, because of the large variability of tissue properties with anatomical site, sex, age and health conditions of the patient undergoing implantation. We investigated the feasibility of defining a quantitative bone structural similarity score based on differences in the structural properties of synthetic grafts and bone tissue. Methods Two biocompatible hydroxyapatite porous scaffolds with different nominal pore sizes were compared with trabecular bone tissues from equine humerus and femur. Images of samples’ structures were acquired by high-resolution micro-computed tomography and analyzed to estimate porosity, pore size distribution and interconnectivity, specific surface area, connectivity density and degree of anisotropy. Youngs modulus and stress at break were measured by compression tests. Structural similarity distances between sample pairs were defined based on scaled and weighted differences of the measured properties. Their feasibility was investigated for scoring structural similarity between considered scaffolds or bone tissues. Results Manhattan distances and Quadrance generally showed sound and consistent similarities between sample pairs, more clearly than simple statistical comparison and with discriminating capacity similar to image-based scores to assess progression of pathologies affecting bone structure. Conclusions The results suggest that a quantitative and objective bone structural similarity score may be defined to help biomaterials scientists fabricate, and surgeons select, the graft or scaffold best mimicking the structure of a given bone tissue.

Development of a Device-Assisted Nerve-Regeneration Procedure in Disruptive Lesions of the Brachial Plexus

Background We describe the development of a new surgical procedure to be used in the treatment of disruptive brachial plexus (BP) lesions. It is centered on an artificial device designed to assist nerve regeneration by providing a confined and protected environment. Nerve fibers can repair inside the device, while the adverse massive scar‐tissue formation is limited to the outside of the device. Methods Steps in the development of the procedure were (1) definition of the rationale, (2) design of the device, (3) choice of an in vivo translational model, (4)refinement of the surgical procedure, and (5) performance of an in vivo pilot study as a proof of concept. An interdisciplinary team from several laboratories was involved in this work over a period of 6 years. Results Results showed the absence of significant scar tissue in the regenerate and the presence of myelinated fibers aligned proximodistally between the stumps. This surgical approach can be seen not only as a definitive treatment but also as an early examination and stabilization before some different surgery will be later performed. It may also be used as additional protection for traditional surgery like end‐to‐end coaptation. Conclusions We conclude that the availability of a suitable device‐assisted early treatment, even if not to be considered definitive, could help in addressing the BP lesions at an earlier stage and this may improve the final outcome. Our evidence justifies further experimentation on this approach.