Lymphatic channel sheet of polydimethylsiloxane for preventing secondary lymphedema in the rat upper limb model

Abstract

Secondary lymphedema is a severe complication of cancer treatment, but there is no effective curative method yet. Lymph node dissection and radiation therapy for cancer treatment may lead to secondary lymphedema, which is a chronic disease induced by malfunction of lymphatic flow. The lymphatic channel sheet (LCS) is an artificial micro‐fluidic structure that was fabricated with polydimethylsiloxane to maintain lymphatic flow and induce lymphangiogenesis. The structure has two‐dimensional multichannels that increase the probability of lymphangiogenesis and allow for relatively easy application. We verified the efficacy of the lymphatic channel sheet through macroscopic and microscopic observation in small animal models, which underwent brachial lymph node dissection and irradiation. The lymphatic channel sheet enabled the successful transport of lymphatic fluid from the distal to the proximal area in place of the removed brachial lymph nodes. It prevented swelling and abnormal lymphatic drainage during the follow‐up period. Lymphangiogenesis was also identified inside the channel by histological analysis after 8 weeks. According to these experimental results, we attest to the roles of the lymphatic channel sheet as a lymphatic pathway and scaffold in the rat upper limb model of secondary lymphedema. The lymphatic channel sheet maintained lymphatic flow after lymph node dissection and irradiation in an environment where lymph flow is cut off. It also relieved symptoms of secondary lymphedema by providing a lymph‐friendly space and inducing lymphangiogenesis.

Static and dynamic analysis of in-vivo imaging for early-detection of lymphedema via near-infrared fluorescence indocyanine green lymphangiography

“…The system was then able to obtain high-accuracy images with high spatial resolution. We tested the spatial resolution and the signal-to-noise ratio (SNR) of this modality using a lymphatic channel sheet (LCS) which is a bio-implantable artificial lymph vessel containing 250-μm microfluidic channels [ 22 ]. The signal-to-noise ratio was 14.8 decibels for background and 10.7 decibels for near-channel area in the resulting NIRF-ICG images obtained with this process (Figure S4A).…”

“…In our present study using lymphedema animal models, the in vivo signal characteristics of lymphatic contraction in lymphedema were observed using the dynamic analysis properties of NIRF-ICG lymphangiography and the results were compared with those obtained via the static analysis that is usually used in clinical practice [ [21][22][23] ]. We induced the lymphatic disruption in the proximal area of in a limb of the animal models (dissection limbs), and the development of lymphedema in the limbs was evaluated using the volume differences with control limbs.…”

In Vivo Dynamic and Static Analysis of Lymphatic Dysfunction in Lymphedema Using Near-Infrared Fluorescence Indocyanine Green Lymphangiography

“…We tested the spatial resolution and the signal-to-noise ratio of this modality using a lymphatic channel sheet, which is a bioimplantable artificial LVs containing 250-μm microfluidic channels. 23 The signal-to-noise ratio was 14.8 decibels for the background and 10.7 decibels for the near-channel area in the resulting NIRF-ICG images obtained with this process (Figure S4A). In spatial resolution analysis, the diameter of the channels in the images (271 μm, 254 μm), which was calculated from the full width at half maximum values of the peaks, was almost identical to the actual diameter (250 μm; Figure S4B).…”

“…In our present study using animal models with lymphatic obstruction, the in vivo signal characteristics of lymphatic contraction in lymphedema were observed using the dynamic analysis properties of NIRF-ICG lymphangiography, and the results were compared with those obtained via the static analysis that is usually used in clinical practice. [22][23][24] We induced the lymphatic disruption in the proximal area of a limb of the animal models (dissection limbs), and the development of lymphedema in the limbs was evaluated using the volume differences with control (normal) limbs. In the NIRF-ICG lymphangiography experiments, static analysis for lymphatic drainage patterns and lymph fluid leakage was conducted in the dissection limbs in comparison to the control limbs.…”

Development of a rat model of lymphedema and the implantation of a collagen-based medical device for therapeutic intervention

“…Microcomputed tomography (microCT) imaging was used to precisely evaluate volumetric changes of lymphedematous and contralateral healthy limb, and lymphoscintigraphy to explore lymph drainage. The 20 Gy irradiation dose was adopted in a forelimb lymphedema study with a two-month follow-up ( 25 ). The hind limb location of the rat model is economically and technically reproducible, thus enabling the investigation of surgical treatments to combat chronic lymphedema.…”