Historically, many potential therapies have failed during the clinical trial phase, often due to unexpected complexities or their inefficacy in practical clinical settings. Advancements in tissue engineering and scaffold development are reducing this translational gap. Moreover, tissue engineering allows research on rare and uncharacterized conditions for which extensive clinical trials may not be feasible.
Optimal oxygen exchange at the cellular level is essential to enable reproducible, scalable production of biological tissues. This article explores the role of oxygen management in tissue engineering and scaffold development and highlights how real-time oxygen monitoring enhances the production of tissues in a controlled, standardized way.
Monitoring cellular activities and the microenvironment
One of the fundamental challenges in tissue engineering is continuously measuring cellular activities, tissue assembly, and functional integration while monitoring the microenvironment within 3D scaffolds, which are generally opaque and thick structures.
Traditionally, measuring cellular activities within scaffolds—such as cell proliferation, differentiation, and interactions—requires invasive techniques like cell harvesting. Once harvested, scientists can analyze molecular functions with the help of specific markers or probes that track changes in gene expression, protein synthesis, and signaling pathways.
Imaging techniques, such as coherence tomography, provide a non-invasive way to visualize cellular and extracellular components within the tissues, however, it has been shown in literature that it falls short of assessing the integrated functionality of these fabricated tissues. For example, neural circuits such as “mini” brains can morphologically look intact and fully differentiated but not capable of firing, acting in synchrony or oscillation. Metabolic and electrical sensors are able to detect these key functional attributes.
Microfluidic devices manage the movement of fluids within controlled environments to mimic physiological conditions like blood flow. This precise control over nutrient delivery and waste removal is essential for supporting the growth and sustainability of tissue cultures, enabling the development of tissues that more closely mimic those found in the body. These devices can also be integrated with biosensors to monitor various parameters of the cell culture environment in real time.
Additionally, biosensors can be embedded directly within the tissues to measure biological and chemical processes. Researchers can then continuously monitor essential parameters of integrated function such as pH and oxygen levels without disrupting scaffold integrity, which is crucial for the industrialization of cell biology.
The importance of oxygen management in tissue engineering
Oxygen gradients within scaffolds must be sufficient to ensure cells survive and perform their essential biological functions. However, this can be problematic in thicker or denser scaffolds, where oxygen diffusion can be restricted, leading to hypoxia (a lack of sufficient oxygen) in the core areas. While hypoxia may promote certain beneficial processes, such as stem cell differentiation and the formation of new blood vessels, it can also induce cellular stress and cell death if prolonged, undermining the viability of engineered tissues.
Too much oxygen, or hyperoxia, can also risk tissue engineering outcomes. Excessive oxygen can cause cells to overproduce reactive oxygen species, which can damage proteins, lipids, and DNA. This disruption in cellular functions can lead to premature cell aging or death. High oxygen levels can also inhibit some cellular processes and disrupt the balance of growth factors and cytokines, altering the developmental signals that cells receive within the scaffold.
Designing scaffolds that promote adequate oxygen penetration without compromising structural integrity or biological function requires innovative approaches, such as incorporating microchannels or using highly porous materials. Understanding the specific oxygen needs of different cell types and developing protocols to maintain these conditions are also crucial for the successful development of tissue-engineered products.
Integrating real-time oxygen monitoring systems offers a promising new solution to some of the challenges of oxygen management in tissue engineering and scaffold development. These label free, non-perturbing biosensors enable continuous detection and adjustment of oxygen levels within the scaffold, thus ensuring and providing a window for the acquisition and maintenance of appropriate tissue functionality in these long-term culture model systems
Real-time monitoring of oxygen levels
Real-time oxygen surveillance allows for the immediate detection of hypoxic or hyperoxic conditions within the scaffold. This feedback can be used to adjust culture conditions, such as increasing or reducing oxygen supply or modifying flow rates in bioreactor systems to ensure even distribution throughout the scaffold.
Continuous data on oxygen and nutrient gradients can also inform iterative improvements in scaffold design. Engineers can adjust porosity, the dimensions of the individual pores within the material, and the distribution of these features based on real-time feedback. This helps optimize the system's physical structure to support better diffusion and cellular viability.
Monitoring systems can be coupled with controlled delivery systems to regulate the supply of oxygen and nutrients based on the detected needs. This could involve adjusting the concentrations of specific nutrients or modulating oxygen levels to mimic physiological conditions that promote desired cellular activities or differentiation patterns.
Integrating these diverse monitoring systems within tissue engineering requires careful consideration to ensure that they do not interfere with the integrity and functionality of the tissues. These systems must be highly biocompatible to prevent any adverse biological responses. They must also be capable of providing high spatial and temporal resolution to effectively capture the dynamic nature of tissue environments. Data analysis tools are also needed to decode the complex interactions between cellular activities and environmental factors, which is key to developing more effective tissue engineering strategies.
Advancements in medical research and clinical applications
Creating viable, functional 3D tissues can benefit medical research, improve discovery and development of pharmaceutical candidates, and increase therapeutic applications of tissue engineering. By effectively managing the oxygen supply within biological tissues, researchers can address some of the most persistent challenges in the field, including issues related to the scalability and reproducibility of tissue constructs. Consistent oxygen conditions ensure that engineered tissues batches remain uniform, which is essential for more precise and predictable responses to pharmaceutical interventions.
Improved oxygen management techniques, including real-time oxygen monitoring, can also help mimic physiological conditions more accurately, leading to the development of tissue models that respond to treatments in ways that are similar to natural tissues. This advancement is crucial to enhancing drug development processes and personalized medicine strategies.
Understanding and controlling oxygen distribution and exchange at various tissue levels remains a critical yet underdeveloped area in tissue engineering. Continued research and deeper insights into this aspect will enhance the viability of engineered tissues and broaden their applications in medical science, ultimately leading to more effective treatments and innovations in patient care.
