2025 AIChE Annual Meeting

(275a) Leveraging 3D Tissue-Engineered Models for Skin Disease Research: Case Studies on Melanoma and Scleroderma

Authors

Lee Yen Feng, University College London
Anna-Dimitra Kataki, University College London
Yubing Hu, Imperial College London, South Kensington
Ali K. Yetisen, Imperial College London, South Kensington
Markella Ponticos, Center for Rheumatology and Connective Tissue Diseases, University College London, Royal Free Campus, London NW3 2PS, UK
Eirini Velliou, University College London
The rapid advancement of 3D tissue-engineered models has the potential to revolutionize the study of skin diseases by offering a more accurate and human-relevant platform compared to traditional 2D models and animal testing.[1-3] This abstract presents two complementary case studies that demonstrate the utility of 3D skin models in advancing our understanding of skin disease pathophysiology and validating innovative diagnostic technologies, namely: (i) a melanoma model for microneedle (MN)-based diagnostics and (ii) a scleroderma model for evaluating diseased skin fibroblast behavior on functionalized scaffolds. Both studies highlight the critical role of biomimetic models in enhancing disease modeling, therapeutic development, and diagnostic innovation for skin-related conditions.

For the first study, we developed a melanoma model that mimics in vivo skin conditions, focusing on its application for the validation of microneedles designed for interstitial fluid (ISF) sampling. Traditional animal models in cancer research face ethical and physiological limitations, and our 3D melanoma model offers a promising alternative.[4] The model is engineered to replicate key skin structures and allows for precise testing of microneedle penetration and biomarker extraction capabilities. Microneedles fabricated from alginate-coated poly(L-lactic acid) (PLLA) were optimized for both mechanical performance and ISF sampling.[5] The microneedles demonstrate exceptional mechanical resilience (yield point> 200N) and efficient sampling capabilities, extracting over 10 µL (>70% swelling capacity) within 5 minutes. Additionally, biocompatibility testing with human dermal fibroblasts and melanoma cells in a 3D model confirms their safety. These microneedles were successfully used to quantify the key melanoma biomarker S100B in the tumor microenvironment, providing unique insights into melanoma interstitial fluid composition.

In the second study, we explored the use of polyurethane (PU) scaffolds functionalized with various proteins to study the behavior of diseased primary fibroblasts in a 3D scleroderma model. Scleroderma, a fibrotic skin disease, is characterized by abnormal fibroblast activation and collagen deposition.[6] By using PU scaffolds functionalized with collagen I and III, we aimed to investigate the impact of protein coatings on fibroblast viability, metabolic activity, and fibrosis-related marker expression, with a particular focus on IL-6, a key marker of fibrosis.[7, 8] Preliminary results indicate that fibroblasts behave differently in response to functionalized scaffolds. This model promises to deepen our understanding of disease-specific cellular responses and provide insights into potential therapeutic interventions for scleroderma.

These two case studies demonstrate the versatility and potential of 3D tissue-engineered models in advancing skin disease research. Both melanoma and scleroderma involve complex cellular behaviours that traditional models often fail to replicate. The 3D models presented here not only provide a more accurate representation of the in vivo environment but also serve as valuable tools for testing and refining innovative diagnostic and therapeutic strategies. Specifically, the melanoma model offers a critical platform for validating microneedle biosensors, while the scleroderma model enables the investigation of cellular responses to functionalized scaffolds within a fibrotic context.

References

[1] Wishart, G.; Gupta, P.; Schettino, G.; Nisbet, A.; Velliou, E. 3d tissue models as tools for radiotherapy screening for pancreatic cancer. Br. J. Radiol. 2021, 94 (1120). DOI: 10.1259/bjr.20201397.

[2] Stanton, D. N.; Ganguli-Indra, G.; Indra, A. K.; Karande, P. Bioengineered Efficacy Models of Skin Disease: Advances in the Last 10 Years. Pharmaceutics 2022, 14 (2), 319. DOI: 10.3390/pharmaceutics14020319.

[3] Zhao, Z.; Chen, X.; Dowbaj, A. M.; Sljukic, A.; Bratlie, K.; Lin, L.; Fong, E. L. S.; Balachander, G. M.; Chen, Z.; Soragni, A.; et al. Organoids. Nature Reviews Methods Primers 2022, 2 (1), 94. DOI: 10.1038/s43586-022-00174-y.

[4] Totti, S.; Ng, K. W.; Dale, L.; Lian, G.; Chen, T.; Velliou, E. G. A novel versatile animal-free 3D tool for rapid low-cost assessment of immunodiagnostic microneedles. Sens. Actuators B Chem. 2019, 296, 126652. DOI: 10.1016/j.snb.2019.126652.

[5] Hu, Y.; Chatzilakou, E.; Pan, Z.; Traverso, G.; Yetisen, A. K. Microneedle Sensors for Point-of-Care Diagnostics. Advanced Science 2024, 11 (12), 2306560. DOI: 10.1002/advs.202306560.

[6] Gyftaki-Venieri, D. A.; Abraham, D. J.; Ponticos, M. Insights into myofibroblasts and their activation in scleroderma: opportunities for therapy? Curr. Opin. Rheumatol. 2018, 30 (6), 581-587. DOI: 10.1097/bor.0000000000000543.

[7] Ponticos, M.; Smith, B. D. Extracellular matrix synthesis in vascular disease: hypertension, and atherosclerosis. J. Biomed. Res. 2013, 28, 25 - 39. DOI: 10.7555/JBR.27.20130064.

[8] Kataki, A.-D.; Gupta, P. G.; Cheema, U.; Nisbet, A.; Wang, Y.; Kocher, H. M.; Pérez-Mancera, P. A.; Velliou, E. G. Mapping Tumor–Stroma–ECM Interactions in Spatially Advanced 3D Models of Pancreatic Cancer. ACS Applied Materials & Interfaces 2025, 17 (11), 16708-16724. DOI: 10.1021/acsami.5c02296.