Publications

[14] Modeling Drug Transport and Absorption in Subcutaneous Injection of Monoclonal Antibodies: Impact of Tissue Deformation, Devices, and Physiology M de Lucio, Y Leng, H Wang, P Vlachos, H Gomez. Int. Journal of Pharmaceutics (submmited for publication), 2024.

The pharmaceutical industry has experienced a remarkable increase in the use of subcutaneous injection of monoclonal antibodies (mAbs), attributed mainly to its advantages in reducing healthcare-related costs and enhancing patient compliance. Despite this growth, there is a limited understanding of how tissue mechanics, physiological parameters, and different injection devices and techniques influence the transport and absorption of the drug. In this work, we propose a high-fidelity computational model to study drug transport and absorption during and after subcutaneous injection of mAbs. Our numerical model includes large-deformation mechanics, fluid flow, drug transport, and blood and lymphatic uptake. Through this computational framework, we analyze the tissue material responses, plume dynamics, and drug absorption. We analyze different devices, injection techniques, and physiological parameters such as BMI, flow rate, and injection depth. Finally, we compare our numerical results against the experimental data from the literature.

[13] A MPET2-mPBPK model for subcutaneous injection of biotherapeutics with different molecule sizes: from local scale to whole-body scale. H Wang, M de Lucio, T Hu, Y Leng, H Gomez. Journal of Controlled Release (submmited for publication), 2023.

We propose the MPET2-mPBPK model to address this issue. This multiscale model couples the MPET2 model, which describes subcutaneous injection at the local tissue scale from a biomechanical view, with a post-injection absorption model at injection site and a minimal physiologically-based pharmacokinetic (mPBPK) model at whole-body scale. Utilizing the principles of tissue biomechanics and fluid dynamics, the local MPET2 model provides solutions that account for tissue deformation and drug absorption in local blood vessels and initial lymphatic vessels during injection. Additionally, we introduce a model accounting for the molecular size effect on the  absorption by blood vessels, and a nonlinear model accounting for the absorption in lymphatic vessels. 

[12] Poro-hyperelastic Characterization and Modeling of Subcutaneous Tissue Under Confined Compression. J Barsimantov, J Payne, M de Lucio, M Hakim, H Gomez, L Solorio, A Buganza. Annals of Biomedical Engineering, 2023.

Porcine subcutaneous samples and gelatin hydrogels from the belly region were tested in a custom confined compression chamber at physiological conditions and physiological strain rates in 5% strain steps with 2600 seconds of stress relaxation between loading steps. Force-time data were used in an inverse finite element approach to obtain material parameters. Tissues and gels were modeled as porous neo-Hookean materials with properties specified via shear modulus, effective solid volume fraction, initial hydraulic permeability, permeability exponent, and normalized moduli for six different time scales of relaxation. The constitutive model was implemented into an isogeometric analysis (IGA) framework to study needle injection

[11] Stabilized isogeometric formulation of the multi-network poroelasticity and transport model (MPET2) for subcutaneous injection of monoclonal antibodies. H Wang, T Hu, Y Leng, M de Lucio, H Gomez. Computer Methods in Applied Mechanics and Engineering, 2023.

The MPET 2 model couples the multi-network poroelastic theory (MPET) with solute transport equations and provides predictions of the material deformation, fluid dynamics, and solute transport in different compartments of a deformable multiple-porosity medium. MPET 2 offers a comprehensive framework for understanding complex porous media across multiple disciplines. Despite the wide range of applications of the model, its numerical discretization has received little attention. Here we propose a stabilized formulation of the MPET 2 model.

[10] Computational modeling of the effect of skin pinch and stretch on subcutaneous injection of monoclonal antibodies using autoinjector devices. M de Lucio, H Wang, Y Leng, AM Ardekani, PP Vlachos, G Shi, H Gomez. Biomechanics and Modeling in Mechanobiology, 2023

Subcutaneous injection of monoclonal antibodies (mAbs) has experienced unprecedented growth in the pharmaceutical industry due to its benefits in patient compliance and cost-effectiveness. However, the impact of different injection techniques and autoinjector devices on the drug’s transport and uptake is poorly understood. Here, we develop a biphasic large-deformation chemomechanical model that accounts for the components of the extracellular matrix that govern solid deformation and fluid flow within the subcutaneous tissue: interstitial fluid, collagen fibers and negatively charged proteoglycan aggregates. We use this model to build a high-fidelity representation of a virtual patient performing a subcutaneous injection of mAbs.

[8] Modeling large-volume subcutaneous injection of monoclonal antibodies with anisotropic porohyperelastic models and data-driven tissue layer geometries. M de Lucio, Y Leng, A Hans, I Bilionis, AM Ardekani, PP Vlachos, H Gomez. Journal of the Mechanical Behavior of Biomedical Materials.

Subcutaneous injection of therapeutic monoclonal antibodies (mAbs) has become one of the fastest-growing fields in the pharmaceutical industry. The transport and mechanical processes behind large volume injections are poorly understood. Here, we leverage a large-deformation poroelastic model to study high-dose, high-speed subcutaneous injection. We account for the anisotropy of subcutaneous tissue using of a fibril-reinforced porohyperelastic model. We also incorporate the multi-layer structure of the skin tissue, generating data-driven geometrical models of the tissue layers using histological data. We analyze the impact of handheld autoinjectors on the injection dynamics for different patient forces.

[5] Isogeometric analysis of subcutaneous injection of monoclonal antibodies. M de Lucio, M Bures, AM Ardekani, PP Vlachos, H Gomez. Computer Methods in Applied Mechanics and Engineering 373, 113550

Subcutaneous injection for self-administration of biotherapeutics, such as monoclonal antibodies, has emerged as a fast-growing field in the pharmaceutical industry. Effective drug delivery in the subcutaneous tissue critically depends on the coupled mechanical and transport processes occurring in the tissue during and after the injection. The details of these processes, however, remain poorly understood; and this explains the growing interest in computational approaches. Notably, there are very few computational studies on subcutaneous injection into three-dimensional porous media that account for tissue deformability. Here, we leverage a poroelastic model to analyze the response of subcutaneous tissue under the flow of a pressurized fluid.

[4] On the importance of tunica intima in the aging aorta: a three-layered in silico model for computing wall stresses in abdominal aortic aneurysms. M de Lucio, Marcos Fernandez García, Jacobo Diaz García, Luis E. Romera Rodríguez, Francisco Álvarez Marcos. Computer Methods in Biomechanics and Biomedical Engineering 24 (5), 467-484

Layer-specific experimental data for human aortic tissue suggest that, in aged arteries and arteries with non-atherosclerotic intimal thickening, the innermost layer of the aorta increases significantly its stiffness and thickness, becoming load-bearing. However, there are very few computational studies of abdominal aortic aneurysms (AAAs) that take into account the mechanical contribution of the three layers that comprise the aneurysmal tissue. In this paper, a three-layered finite element model is proposed from the simplest uniaxial stress state to geometrically parametrized models of AAAs with different asymmetry values.