Decellularized Dermis ECM-Based Melanoma-on-a-Chip Model with Integrated Lymphatic and Vascular Networks for High-Throughput Drug Testing

ACS Applied Bio Materials, vol. 9, pp. 2971–2979

Abstract

High Resolution Image Download MS PowerPoint Slide Developing effective treatments for malignant melanoma remains a complex challenge, requiring models that accurately replicate the tumor microenvironment to study metastasis and drug response. Whereas in vitro models have become essential tools due to their tunability and controllability, systems incorporating both biomimetic extracellular matrices (ECM) and vascular components are more complex and therefore remain challenging. In this study, we present an in vitro melanoma model comprising a dermal decellularized ECM (dECM) together with both blood and lymphatic vessels, cultured within a commercial microfluidic platform that enables high-throughput testing. Our system features a triculture melanoma spheroid embedded within a dermis dECM hydrogel and flanked by vascular structures, effectively recreating key aspects of the melanoma microenvironment, as confirmed by immunostaining for canonical markers and morphological resemblance. Proof-of-concept drug testing demonstrates the model’s suitability for high-throughput drug screening, as validated by cytotoxicity assays. The complexity and biomimetic nature of this model provides a robust platform for studying melanoma progression, tumor-vascular interactions, and therapeutic responses, ultimately offering a promising alternative for in vitro melanoma research and drug development.

Authors 7

1. Paula Vázquez-Aristizabal

   CIC biomaGUNE · Biogipuzkoa Health Research Institute · Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine

   Affiliation as printed

   Basque Research and Technology Alliance (BRTA)

   Biogipuzkoa Health Research Institute

   Biomedical Research Networking Center in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN)

   CIC biomaGUNE

   Stem Cells & Aging Group

2. Inazio Arriola-Alvarez

   Biogipuzkoa Health Research Institute

   Affiliation as printed

   Biogipuzkoa Health Research Institute

   Stem Cells & Aging Group

3. Malou Henriksen‐Lacey

   CIC biomaGUNE · Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine

   Affiliation as printed

   Basque Research and Technology Alliance (BRTA)

   Biomedical Research Networking Center in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN)

   CIC biomaGUNE

4. Sonia Alonso‐Martín

   Instituto de Salud Carlos III · Biomedical Research Networking Center on Neurodegenerative Diseases · Biogipuzkoa Health Research Institute

   Affiliation as printed

   Biogipuzkoa Health Research Institute

   CIBERNED, ISCIII (CIBER, Carlos III Institute, Spanish Ministry of Sciences and Innovation)

   Stem Cells & Aging Group

5. Lenie van den Broek Aachen Mimetas BV

   Mimetas (Netherlands)

   Affiliation as printed

   Mimetas BV, De Limes 7, 2342DH Oegstgeest, The Netherlands

6. Luis M. Liz‐Marzán corresponding

   Ikerbasque · CIC biomaGUNE · Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine · Universidade de Vigo

   Affiliation as printed

   Basque Research and Technology Alliance (BRTA)

   Biomedical Research Networking Center in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN)

   CIC biomaGUNE

   Cinbio, Universidade de Vigo

   Ikerbasque Basque Foundation for Science

7. Ander Izeta corresponding

   Biogipuzkoa Health Research Institute · Donostiako Unibertsitate Ospitalea · Universidad de Navarra

   Affiliation as printed

   Advanced Therapies Unit

   Biogipuzkoa Health Research Institute

   Donostia University Hospital

   School of Engineering

   Stem Cells & Aging Group

   Tecnun-University of Navarra