Neural Engineering

The Neural Engineering Research Group develops advanced 3D in vitro tissue and organ-on-chip models designed to capture the structural and functional complexity of human tissues. Our work combines biomaterials engineering, microfabrication, and multicellular biology to create physiologically relevant platforms for studying tissue development, function, and disease.

At the core of our research is the creation of engineered microenvironments using natural and synthetic hydrogels, including collagen, Matrigel, fibrin-based matrices, PEGDA, and polyacrylamide. These materials are structured to enable precise spatial organization of cells, allowing controlled reconstruction of tissue architecture within microfluidic systems.

A defining focus of the group is the incorporation of peripheral innervation into engineered tissues. We have established a robust 3D human peripheral sensory nerve model based on iPSC-derived sensory neurons and Schwann cells, with quantitative readouts of axonal organization, oriented growth, myelination, and protein expression. This platform is used to investigate mechanisms regulating nerve development, including structural guidance, direct cell–cell interactions, and paracrine signalling.

Building on this nerve model, we develop integrated multisystem platforms, including:

Neurovascular models, examining coordinated neural and endothelial network growth and their functional interdependence.
Neuro-immune models, combining sensory neurons with innate immune cells (e.g. macrophages, dendritic cells) to study bidirectional interactions between inflammation, nerve growth, and neural activity.

To support these systems, we have developed a novel polymer-based templating technology that enables rapid formation of cell-lined microchannels within 3D hydrogels. Initially designed for nerve repair–inspired architectures, this approach has been extended to generate endothelialized, perfusable microvascular networks. Current applications include blood–brain barrier modelling, with strong potential for adaptation to other vascularized and innervated tissues.

In parallel, the group develops a range of functional tissue-specific in vitro models that serve as modular platforms for subsequent integration of neural, vascular, and immune components. All models incorporate patient material, often culturing these cells as organoids to expanding these cell sources for use within the models. These include:

Human engineered skin equivalents, incorporating epidermal and dermal compartments, with ongoing development of improved sensory innervation and perfusable vascular structures.
Perfusable tubular intestinal models with epithelial, stromal, and sensory neuronal components, used to study barrier function and multicellular regulation.
Perfusable tubular oviduct models (ERC Starting Grant), designed to investigate reproductive function and tissue responses to infection, including Chlamydia, with planned immune integration.

Complementing platform development, the group places strong emphasis on advanced functional readouts and imaging. We operate a dedicated multiphoton microscopy system optimized for 3D organ-on-chip models, incorporating second and third harmonic generation (SHG/THG) to enable label-free monitoring of tissue architecture, extracellular matrix organization, and dynamic cellular interactions.

Overall, our research provides versatile, modular human-relevant in vitro systems that are well suited for collaborative projects focused on tissue–tissue interactions, neurobiology, inflammation, vascular biology, infection, and translational model development. We are particularly interested in contributing enabling technologies, complex 3D platforms, and integrated innervated and vascularized tissue models to interdisciplinary consortia.

Selected publications

Kim, M. Ślęczkowska, B. Nobre, and P. Wieringa. 2025. “Study Models for Chlamydia Trachomatis Infection of the Female Reproductive Tract,” 1–21.
Malheiro, M. Thon, A. Filipa Lourenço, A. Seijas Gamardo, A. Chandrakar, S. Gibbs, P. Wieringa, and L. Moroni. “A Humanized In Vitro Model of Innervated Skin for Transdermal Analgesic Testing.” Macromolecular Bioscience. 2023; 23 (1): 1–11.
Malheiro, A. Seijas-Gamardo, A. Harichandan, C. Mota,P. Wieringa, L. Moroni. Development of an in vitro biomimetic peripheral neurovascular platform. ACS Applied Materials & Interfaces. 2022; vol 14, No. 28.
Malheiro, A. Harichandan, J. Bernardi, A. Seijas-Gamardo, G.F. Konings, P.G.A. Volders, A. Romano, C. Mota, P. Wieringa, L. Moroni. 10.1088/1758-5090/ac36bf "3D culture platform of human iPSCs- derived nociceptors for peripheral nerve modeling and tissue innervation." Biofabrication. 2022; 14(1).