Lymphatic uptake of biotherapeutics through a 3D hybrid discrete-continuum vessel network in the skin tissue

Han, Dingding; Li, Chenji; Araimdeh, Soroush; Sree, Vivek D.; Rahimi, Ehsan; Tepole, Adrián Buganza; Ardekani, Arezoo M.

doi:10.1016/j.jconrel.2022.12.045

Cited by 8 publications

(17 citation statements)

References 60 publications

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“…A comprehensive model for the extravascular transport of fluid and drug solutes and the transvascular exchange in the tissue is described for both the continuum medium over the length scale of O (1 cm) and the discrete vessels over the length of O (100 µm) in this Section [11,13].…”

Section: Transport Equationsmentioning

confidence: 99%

“…In our previous works [11][12][13], the convective transport of drug solutes is driven by the interstitial fluid pressure (IFP) into the lymphatic system, which plays an important role in drug absorption through SC injection. The mechanical process of the injection and its effect on pressure build-up and relaxation are essential to understand the fluid flow and drug clearance at the injection site [12,14].…”

Section: Introductionmentioning

confidence: 99%

“…The mechanical process of the injection and its effect on pressure build-up and relaxation are essential to understand the fluid flow and drug clearance at the injection site [12,14]. The diffusion across the discrete heterogeneous lymphatic vessel network significantly affects the lymphatic uptake [13]. However, the computation cost is expensive for a multi-scale problem with both a heterogeneous explicit vessel network and the constitutive equations included, where the vessels of radius O (10 µm) are embedded in a domain of size O (1 cm).…”

Section: Introductionmentioning

confidence: 99%

“…Our previous studies numerically investigate the contribution of large interstitial pressure to drug absorption during and after the injection [11,12]. A hybrid discrete-continuum vessel network model is developed to describe the diffusion and convection of drug solutes across the vessel wall [13]. Although the poroelastic model can simulate the deformation of the soft subcutaneous tissue, the computation is expensive after coupling with transport equations and instability issues may occur [12].…”

Section: Introductionmentioning

confidence: 99%

“…For lymphatic vessels, LECs are loosely connected and have a primary valve structure to ensure the one-directional fluid flows from the interstitial space into the lymphatics. In our previous work [13], three different transport conditions are used to investigate solute transport across the lymphatic vessel membrane, including the Kedem-Katchalsky model. In [26,27], an integral form of the modified Kedem-Katchalsky formulation is used to study dermal clearance through the blood and lymphatic vessels.…”

Section: Introductionmentioning

confidence: 99%

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Solute Transport across the Lymphatic Vasculature in a Soft Skin Tissue

Han

Huang

Rahimi

et al. 2023

Biology

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Convective transport of drug solutes in biological tissues is regulated by the interstitial fluid pressure, which plays a crucial role in drug absorption into the lymphatic system through the subcutaneous (SC) injection. In this paper, an approximate continuum poroelasticity model is developed to simulate the pressure evolution in the soft porous tissue during an SC injection. This poroelastic model mimics the deformation of the tissue by introducing the time variation of the interstitial fluid pressure. The advantage of this method lies in its computational time efficiency and simplicity, and it can accurately model the relaxation of pressure. The interstitial fluid pressure obtained using the proposed model is validated against both the analytical and the numerical solution of the poroelastic tissue model. The decreasing elasticity elongates the relaxation time of pressure, and the sensitivity of pressure relaxation to elasticity decreases with the hydraulic permeability, while the increasing porosity and permeability due to deformation alleviate the high pressure. An improved Kedem–Katchalsky model is developed to study solute transport across the lymphatic vessel network, including convection and diffusion in the multi-layered poroelastic tissue with a hybrid discrete-continuum vessel network embedded inside. At last, the effect of different structures of the lymphatic vessel network, such as fractal trees and Voronoi structure, on the lymphatic uptake is investigated. In this paper, we provide a novel and time-efficient computational model for solute transport across the lymphatic vasculature connecting the microscopic properties of the lymphatic vessel membrane to the macroscopic drug absorption.

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Section: Transport Equationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Solute Transport across the Lymphatic Vasculature in a Soft Skin Tissue

Han

Huang

Rahimi

et al. 2023

Biology

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Computational fluid dynamic modeling of the lymphatic system: a review of existing models and future directions

Jayathungage Don,

Safaei,

Maso Talou

et al. 2023

Biomech Model Mechanobiol

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Historically, research into the lymphatic system has been overlooked due to both a lack of knowledge and limited recognition of its importance. In the last decade however, lymphatic research has gained substantial momentum and has included the development of a variety of computational models to aid understanding of this complex system. This article reviews existing computational fluid dynamic models of the lymphatics covering each structural component including the initial lymphatics, pre-collecting and collecting vessels, and lymph nodes. This is followed by a summary of limitations and gaps in existing computational models and reasons that development in this field has been hindered to date. Over the next decade, efforts to further characterize lymphatic anatomy and physiology are anticipated to provide key data to further inform and validate lymphatic fluid dynamic models. Development of more comprehensive multiscale- and multi-physics computational models has the potential to significantly enhance the understanding of lymphatic function in both health and disease.

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