Blood-Brain Barrier (BBB) Model Development
Protheragen specializes in building complex models of the blood-brain barrier (BBB) which take into account both the physiological and pathological conditions. This aids researchers in bridging the translational chasm experienced in preclinical studies. These models are crucial for determining the effectiveness, toxicity, and transport mechanisms of a drug, providing better predictions of how a human would respond.
Introduction to Blood-Brain Barrier (BBB) Models
The blood-brain barrier (BBB) is a highly selective, semi-permeable barrier differentiating between the blood and the extracellular fluid surrounding the brain, thus maintaining the homeostasis of the central nervous system (CNS). The complex structure of the BBB comprises pericytes, astrocytes, endothelial cells and basement membrane, which pose great obstacles to the delivery of therapeutic agents and the study of relevant neurological processes. For studying neurovascular interactions, drug transport across the BBB, drug permeability, and disease mechanisms, the models of the BBB serve as the essential tools.
Fig.1 In vitro models of the blood-brain barrier (BBB). (Ciofani, Gianni, et al., 2023)
Types of Blood-Brain Barrier (BBB) Models
The systems of the blood-brain barrier (BBB) models are divided into 2D and 3D systems. More economical 2D models use cell monolayers which are suitable for high-throughput screening since they are grown on flat surfaces, but lack any physiological accuracy. Simulating blood flow and integrating various cells and supportive structures into microfluidic chips, bioprinted structures, and organoids transforms them into more advanced 3D models which better mimic real conditions of the brain. These models are more effective when researching complex diseases and developing drugs.
| Model Types | 2D BBB Models | 3D BBB Models |
| Structure | Monolayer of cells on a flat surface. | Multi-cellular, layered structures. |
| Cell Complexity | Limited co-culture, typically endothelial cells with astrocytes/pericytes. | Advanced co-cultures including endothelial cells, pericytes, astrocytes, neurons, ECM components, and more. |
| Physiological Relevance | Lacks shear stress, 3D cell-cell interactions, and tissue-like architecture. | Mimics vascular shear stress, cell-matrix interactions, and in vivo-like morphology. |
| TEER Measurement | Standardized but static; may overestimate barrier integrity. | Dynamic, real-time monitoring possible. |
| Applications | High-throughput drug screening and basic permeability studies. | Disease modeling and personalized medicine. |
Our Services
At Protheragen, we offer tailored blood-brain barrier (BBB) model development services that may serve to fast track the development of therapeutics for rare neurological disorders. Our advanced in vitro systems provide an accurate preclinical research platform that assesses drug permeability, neurotoxic properties, and efficacy. With custom 2D or 3D BBB models, we aim to support our pharmaceutical partners in addressing the obstacles faced with central nervous system (CNS) drug development.
2D Blood-Brain Barrier (BBB) Model Development Services
Protheragen's standardized 2D BBB models utilize primary human brain microvascular endothelial cells (HBMECs) or immortalized cell lines (hCMEC/D3), cultured on collagen-coated Transwell inserts to form tight junction-restricted monolayers. The models are validated through TEER measurements and paracellular permeability assays. For enhanced physiological relevance, we offer co-culture systems with human astrocytes/pericytes to better mimic neurovascular unit interactions.
3D Blood-Brain Barrier (BBB) Model Development Services
Microfluidic BBB models use chip designs that replicate physiological shear stress and three-dimensional neurovascular architecture. These systems co-culture HBMECs with astrocytes and pericytes in perfusable microchannels, achieving TEER values exceeding 800 Ω·cm². This platform enables real-time analysis of barrier integrity and polarized drug transport, and is particularly useful for studying rare neurological diseases with a vascular component.
3D Bioprinted BBB Models
Our bioprinted BBB models employ extrusion-based printing of bioinks containing HBMECs, pericytes, and neural stem cells in spatially controlled ECM-mimicking hydrogels. The process creates luminal structures with 50-100μm resolution, permitting quantification of cell-specific barrier contributions through compartmentalized assays. These models demonstrate 40% higher P-gp activity than 2D systems and successfully model amyloid-beta trafficking in Alzheimer's research.
We generate iPSC-derived BBB organoids by stepwise differentiation of endothelial/neural progenitors in 3D Matrigel, forming self-organizing neurovascular units with functional tight junctions. The models incorporate patient-specific mutations for rare diseases, exhibiting in vivo-like perivascular macrophage interactions. RNA-seq validation confirms >80% transcriptomic alignment with human BBB tissue, making them ideal for personalized medicine approaches in neurological disorders.
The BBB models developed by Protheragen provide an experimental platform that complies with ethical and regulatory guidelines for reliable pharmacodynamic (PD), pharmacokinetic (PK) and toxicology studies. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Ciofani, Gianni, et al. "Roadmap on nanomedicine for the central nervous system." Journal of Physics: Materials 6.2 (2023): 022501.