The ExcellMater Project: Engineering the Future of Biomedicine with 3D Cell Cultures
Revolutionizing pharmaceutical research and biomedical applications through advanced biomaterials and three-dimensional cell culture systems
Introduction
What if the very tools scientists use to study diseases and test new drugs have been fundamentally flawed for decades? For years, biological research has relied heavily on two-dimensional (2D) cell cultures—cells grown in flat, single layers on plastic surfaces. While this approach has contributed valuable knowledge, it suffers from a critical limitation: it doesn't mimic how cells actually live and interact within the three-dimensional architecture of the human body. This discrepancy is now recognized as a major reason why promising drug candidates often fail when moved from laboratory testing to human clinical trials 1 .
Key Insight
Less than 5% of anticancer agents that show promise in conventional 2D models ultimately gain regulatory approval for human use 1 .
Enter three-dimensional (3D) cell culture systems—revolutionary technologies that allow cells to grow in all three dimensions, creating microenvironments that closely resemble living tissues. These advanced systems are poised to transform biomedical research, and at the forefront of this revolution is the ExcellMater project, an ambitious European Union-funded initiative that seeks to excel materials engineering for medical devices through international collaboration 3 . By developing sophisticated biomaterials and 3D culture systems, ExcellMater aims to bridge the gap between laboratory research and real-world clinical applications, potentially accelerating the development of more effective treatments and bringing us closer to the promise of truly personalized medicine.
Why 3D Cell Culture Matters: Beyond the Flat World
To appreciate the significance of projects like ExcellMater, it's essential to understand the critical differences between traditional 2D cell culture and emerging 3D systems.
The Limitations of Flat Biology
In a traditional 2D culture, cells are forced to adapt to an artificial, flat environment that poorly represents their natural surroundings in the body. This distortion affects multiple aspects of cell behavior:
- Morphology and Architecture: Cells in 2D cultures adopt flattened, stretched shapes unlike their natural forms 1
- Cell Signaling and Communication: The spatial organization of receptors and signaling molecules is disrupted
- Gene Expression and Function: Cells in 2D often show different patterns of gene expression compared to their in vivo counterparts 4
- Drug Responses: Compounds that appear effective in 2D cultures may fail in actual tissues due to these fundamental differences 1
The Third Dimension: Mimicking Living Tissues
In contrast, 3D cell culture systems allow cells to grow and interact in a three-dimensional space that closely resembles their natural microenvironment. This simple but profound shift enables:
- Natural Cell Morphology: Cells maintain their proper shape and organization 1
- Complex Cell Interactions: Cells can form proper connections with neighbors in all directions
- Physiological Gradients: Nutrients, oxygen, and signaling molecules distribute as they would in real tissues
- Authentic Drug Responses: Therapeutic compounds penetrate and interact with cells in a more realistic manner 4
Comparison of 2D vs 3D Cell Culture Systems
| Characteristic | 2D Culture | 3D Culture | Biological Significance |
|---|---|---|---|
| Cell Environment | Flat, rigid surface | Three-dimensional, flexible space | 3D allows natural cell shape and organization |
| Cell-Cell Interactions | Primarily lateral | Omnidirectional, more natural | Better mimics tissue architecture |
| Nutrient/Oxygen Gradients | Uniform distribution | Physiological gradients present | Creates metabolic heterogeneity like real tissues |
| Drug Resistance | Often artificially sensitive | More clinically relevant resistance | Better predicts treatment efficacy |
| Gene Expression | Often aberrant or altered | More physiologically normal | More accurate disease modeling |
| Lifespan | Typically less than 1 week | Can be maintained for several weeks | Allows longer-term studies |
Research Impact
The physiological relevance of 3D cultures extends to their ability to mimic the extracellular matrix (ECM)—the complex network of proteins and carbohydrates that provides structural and biochemical support to surrounding cells. In living tissues, the ECM is not merely a passive scaffold but an active participant in cellular behavior, influencing everything from cell differentiation to drug resistance 4 7 .
The ExcellMater Project: An International Collaboration for Biomedical Advancement
The ExcellMater project represents a coordinated effort to address the challenges in biomaterials development and 3D cell culture technology. Funded by the European Union's Horizon 2020 research and innovation programme, this initiative aims to increase the scientific and technological capacity of the Faculty of Technology and Metallurgy (FTM) at the University of Belgrade by facilitating knowledge exchange with leading international institutions 3 .
Goals and Mission
Excel in materials engineering for medical devices with focus on translational research, commercialization, and clinical applications.
Collaborative Structure
International consortium with complementary expertise from institutions across Europe.
Knowledge Exchange
Short-term staff visits, student exchanges, seminars, workshops, and summer schools.
Project Consortium Partners
University of Belgrade
SerbiaAalto University
FinlandUniversity of Eastern Piedmont
ItalyAO Research Institute Davos
SwitzerlandCross-Pollination Approach
This collaborative framework enables the cross-pollination of ideas and techniques essential for tackling the complex challenges at the intersection of materials science, cell biology, and clinical medicine.
A Closer Look at a Key Experiment: Developing Bioactive Nanofibers for Wound Healing
To illustrate the type of research enabled by the ExcellMater project, let's examine a specific experiment focused on developing advanced wound dressing materials using electrospun polycaprolactone (PCL) nanofibers functionalized with natural plant extracts.
Methodology: Step by Step
Polymer Solution Preparation
Researchers first dissolved medical-grade polycaprolactone (PCL)—a biodegradable polyester—in an appropriate solvent to create a polymer solution 6 .
Bioactive Incorporation
An extract from Achillea millefolium (yarrow plant), known for its anti-inflammatory and antioxidant properties, was incorporated into the polymer solution 6 .
Electrospinning Process
The solution was loaded into a syringe and subjected to high voltage, creating an electrically charged jet that solidified into ultra-thin nanofibers collected on a grounded plate 6 .
Material Characterization
The resulting nanofibrous mats were analyzed for their morphology, mechanical properties, chemical composition, and bioactivity 6 .
Biological Testing
The materials were sterilized and tested for their ability to support cell growth and function using human skin cells in 3D culture conditions.
Results and Analysis
The experiment yielded promising results across multiple parameters:
| Parameter | Standard PCL Nanofibers | PCL + Yarrow Extract Nanofibers | Significance |
|---|---|---|---|
| Fiber Diameter | 250-300 nm | 280-330 nm | Maintained nanofibrous structure |
| Antioxidant Activity | Minimal | Significant increase | Provides cellular protection |
| Antibacterial Efficacy | None | Against common wound pathogens | Reduces infection risk |
| Mechanical Properties | Baseline | Improved strength and flexibility | Better durability for clinical use |
| Cell Compatibility | Good | Enhanced cell attachment and growth | Promotes tissue regeneration |
Experimental Insight
The incorporation of yarrow extract not only introduced beneficial bioactive properties but surprisingly also enhanced the mechanical characteristics of the material—an unexpected advantage that underscores the value of such exploratory research 6 .
This experiment exemplifies the ExcellMater approach: starting with fundamental materials engineering, enhancing functionality with natural bioactive compounds, and rigorously testing the resulting products in biologically relevant 3D culture systems to develop solutions with genuine clinical potential.
The Scientist's Toolkit: Essential Materials for Advanced 3D Cell Culture
The development of sophisticated 3D culture systems relies on a diverse array of specialized materials and technologies. Here are some key components in the research toolkit:
| Material/Technology | Function | Examples/Applications |
|---|---|---|
| Natural Polymers | Provide biologically recognized scaffolding | Collagen, alginate, fibrin - used for hydrogel formation |
| Synthetic Polymers | Offer tunable mechanical and chemical properties | Polycaprolactone (PCL), polylactic acid (PLA) - used for electrospun scaffolds |
| Bioactive Additives | Enhance biological functionality | Plant extracts (yarrow), growth factors, antimicrobial agents |
| Electrospinning Systems | Create nanofibrous scaffolds that mimic natural ECM | Production of wound dressing materials, tissue engineering scaffolds |
| Bioreactors | Provide dynamic culture conditions with controlled parameters | Perfusion systems for nutrient/waste exchange, mechanical stimulation devices |
| Stem Cells | Offer self-renewal and differentiation potential | Adipose-derived stem cells (ASCs), pluripotent stem cells for tissue modeling |
3D Culture Technology Adoption
Growing adoption of 3D culture technologies in biomedical research over the past decade
Broader Implications and Future Directions
The work pioneered by initiatives like ExcellMater extends far beyond the laboratory, with potentially transformative implications for multiple areas of medicine and healthcare.
Advancing Disease Modeling and Drug Development
One of the most immediate applications of improved 3D culture systems is in the realm of drug discovery and development. By providing more physiologically relevant models, these systems can:
- Improve Predictive Accuracy: Better identify promising drug candidates earlier in the development process 1
- Reduce Animal Testing: Provide superior human-relevant data that may complement or reduce reliance on animal models 4
- Uncover Resistance Mechanisms: Model the complex microenvironmental factors that contribute to treatment resistance in conditions like cancer 7
Personalized Medicine and Regenerative Applications
Perhaps even more exciting is the potential for these technologies to enable truly personalized medical approaches. Researchers can use patient-derived cells to create personalized disease models and identify the most effective treatments for each individual 2 .
Furthermore, 3D cultures hold tremendous promise for tissue engineering and regenerative medicine. By replicating the natural tissue environment and providing a scaffold for cell growth, 3D cultures pave the way for regenerating damaged tissues, offering hope for treating burns, organ failure, and musculoskeletal injuries 2 .
Impact of 3D Culture Systems on Drug Development Pipeline
Comparison of drug development success rates using traditional 2D vs advanced 3D culture systems
Conclusion: Building a Three-Dimensional Future in Biomedicine
The ExcellMater project represents more than just an isolated scientific initiative—it embodies a broader shift in how we approach biological research and medical innovation. By recognizing that cells exist not as flat, isolated entities but within complex three-dimensional communities, and by developing the materials science and engineering capabilities to recreate these environments in the laboratory, researchers are closing the gap between experimental models and living systems.
International Collaboration
Through its focus on international collaboration, knowledge exchange, and capacity building, the project not only advances specific biomaterials and technologies but also cultivates the scientific expertise necessary to sustain this progress into the future.
Future Potential
As 3D culture systems continue to evolve—incorporating ever-more sophisticated biomaterials, multiple cell types, and dynamic culture conditions—they promise to accelerate the development of novel therapeutic strategies.
The transition from 2D to 3D in cell culture represents more than just adding a dimension—it marks a fundamental evolution in our ability to understand and manipulate biological systems for human benefit. With initiatives like ExcellMater leading the way, the future of biomedicine looks increasingly three-dimensional, with the potential to transform how we study disease, develop drugs, and ultimately treat patients.