Researchers have developed a novel method for creating microscopic, hollow tubes that can be integrated into bioengineered tissues to function as primitive blood vessels. This breakthrough, led by a team at Binghamton University, addresses one of the most significant hurdles in tissue engineering: supplying oxygen and nutrients to complex, three-dimensional cell structures. By improving the internal plumbing of these artificial tissues, the new technique could enable the development of larger, more functional, and more realistic organ models for research and clinical applications.
The core problem in growing tissues in the lab is that cells, like those in our own bodies, require a constant blood supply to survive. Without a vascular system, engineered tissues are limited in size and complexity, often developing necrotic, or dead, regions at their core. This new approach utilizes a specialized nanomanufacturing process to build a network of microtubes within a hydrogel matrix, effectively creating a circulatory system that enhances the distribution of essential nutrients throughout the entire structure, paving the way for more sophisticated and viable engineered organs.
The Challenge of Sustaining Engineered Tissues
For decades, biomedical scientists have pursued the goal of creating living human tissue in the laboratory. These bioengineered tissues serve as crucial tools for drug testing, disease modeling, and eventually, therapeutic implants. However, scaling these tissues up from simple, thin layers of cells to complex, three-dimensional structures mimicking a real organ has been a persistent challenge. The primary obstacle is vascularization—the process of growing a network of blood vessels.
In the human body, a vast and hierarchical network of arteries, veins, and capillaries delivers oxygen and nutrients while removing waste products from every cell. Replicating this intricate system is beyond the capabilities of current technology. While 3D printing can create larger vessel-like structures, recreating the fine, microscopic capillaries that permeate deep tissue has been difficult. Without this microvasculature, cells deep within an engineered construct are starved of sustenance and quickly die off, limiting the functional size of the tissue. This limitation has significantly slowed progress in creating viable, lab-grown organs like kidneys, livers, or hearts for transplantation or research.
A Novel Microfabrication Technique
To overcome this limitation, researchers at Binghamton University’s Thomas J. Watson College of Engineering and Applied Science developed a sophisticated method for building an artificial vascular system from the ground up. The team, led by Assistant Professors Ying Wang and Yingge Zhou, focused on creating precisely sized microtubes that could be dispersed throughout a tissue scaffold.
Electrospinning and Material Selection
The manufacturing process begins with electrospinning, a technique that uses a strong electric field to draw ultra-fine fibers from a liquid polymer solution. This method allows for the creation of structures on a microscopic scale, far smaller than what is possible with conventional 3D printing. The researchers chose two common, inert biomedical compounds for their microtubes: polyethylene oxide (PEO) and polystyrene (PS).
The process involves creating a solid fiber with a core made of one material and a shell made of the other. “The microtube is between 1 to 10 microns,” stated Zhou. For comparison, a human hair is typically 70–100 microns thick. Once the solid fibers are formed through electrospinning, the team dissolves the inner core, leaving behind a hollow, seamless tube. These long tubes are then broken down into shorter segments using ultrasonic vibrations, allowing them to be evenly distributed within the tissue medium.
Constructing an Artificial Vascular Network
Once fabricated, the microscopic tubes are integrated into a composite hydrogel. Hydrogels are water-based gels that provide a supportive, three-dimensional environment for cells to grow in, mimicking the natural extracellular matrix of living tissue. By embedding the microtubes into this gel, the researchers effectively create a pre-fabricated vascular network within the scaffold before cells are even introduced.
This method represents a significant departure from other approaches that rely on encouraging cells to self-assemble into vascular structures, a process that can be slow and unreliable. The Binghamton team’s technique ensures that a primitive circulatory system is in place from the very beginning, ready to transport fluid throughout the engineered tissue. This proactive approach ensures that as the tissue grows and becomes denser, the foundational plumbing is already established to support its metabolic needs.
Experimental Results and Validation
To test the effectiveness of their artificial vascular system, the research team conducted experiments using fluorescent microbeads to track fluid flow through the engineered tissues. By comparing tissues grown in hydrogels containing the microtubes to those without, they could visualize and measure how well fluids were distributed. The results, published in the journal Biomedical Materials, demonstrated a clear improvement in the tissues containing the microtubes.
The network of hollow channels successfully transported the microbeads throughout the tissue structure, indicating that they could effectively function as a primitive circulatory system. This enhanced distribution ensures that a greater volume of cells receives the necessary oxygen and nutrients to remain viable and functional. The presence of the microtubes prevented the formation of necrotic cores, enabling the tissues to remain healthier and potentially grow to a larger size than previously possible.
Future Directions in Organ Engineering
The successful demonstration of this technology opens several promising avenues for future research. The team plans to investigate how modifying the dimensions and shapes of the microtubes could affect vascular outcomes. By tuning these properties, it may be possible to create vascular networks tailored to the specific needs of different types of engineered tissues. For example, the dense, complex vasculature of a liver would have different requirements than the specialized vessels of the brain.
Organ-Specific Applications
One of the most exciting potential applications is in the development of organ-specific microvasculature. The researchers aim to model the blood-brain barrier, a highly selective membrane that separates the circulatory system from brain tissue. Creating an accurate model of this barrier is essential for developing new treatments for brain tumors and neurodegenerative diseases like Alzheimer’s or Parkinson’s. A functional, vascularized brain tissue model would allow scientists to test how different drugs cross the barrier and affect brain cells in a controlled, realistic environment.
Ultimately, the goal is to move beyond single-tissue models and toward more complex, multi-organ systems. “If we perfect this technology, we can assemble not only a single organ but multiple organs as a living system based on human cells,” Wang explained. Such a “human-on-a-chip” system would revolutionize preclinical drug trials and provide unprecedented insights into how different organ systems interact, all without the need for animal or human testing. This research marks a critical step toward bringing the physiological relevance of engineered tissues closer to that of the human body itself.