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Next-Gen Cell Therapy Device (Monthly Spin-Off #5)


Bio-Spun™ Cell Chamber –

Using the Body’s Normal Functions to Deliver a Targeted Therapy


Overview

Chronic disease is a broad term that is used to describe a condition that typically lasts for more than one year and requires ongoing medical attention (1). Diabetes, liver disease, Crohn’s disease, Alzheimer’s and Parkinson’s disease are examples of chronic diseases that often require long-term treatment to manage daily symptoms that affect the patient’s quality of life and often cause complications that can shorten their life expectancy. According to the Centers of Disease Control and the World Health Organization, chronic diseases are the leading cause of death in the United States and are the major cause of premature death around the world (2).


One of the main issues that comes with managing a patient with a chronic disease is that their treatment relies heavily on their compliance for the proposed treatment itself. Patient compliance can be affected by many factors such as

treatment complexity, psychosocial factors (beliefs, motivation, attitude), patient-prescriber relationship, health literacy, inability to take time off from work, patient knowledge, physical difficulties, tobacco or alcohol intake and/or forgetfulness (3). For example, some diseases such as Crohn’s disease and diabetes require subcutaneous injections for drug delivery which are often administered by the patients themselves. Self-injections rely heavily on patient compliance which can be reduced if the patient has a negative experience while administering the drug and could potentially impact their treatment outcome (4). For treatment of this disease as well as other chronic diseases, the goal is to maintain a consistent therapeutic level of the drug in the body as compared to having spikes in the dosing, which is not good for the patient (Figure 1). A device that would significantly reduce the need for patient compliance, provide a steady therapeutic treatment over an extended period of time and can be implanted and removed in a minimally-invasive fashion would be an important tool in the treatment of chronic disease.


Development of the Bio-Spun™ Cell Chamber


BioSurfaces recognized that a void existed in the ability to help patients remain compliant with their respective treatment. We hypothesized that our Bio-Spun™ materials could be used as a vehicle to deliver cells into the body, serve to protect them from the body’s immune response and permit the device to be removed if necessary. The Bio-Spun™ Cell Chamber which is made using our proprietary electrospinning technology, is comprised of very small fibers that look like the body’s natural scaffold used to grow cells known as the extracellular matrix (Figure 2). The chamber was designed to hold living cells that release therapeutic proteins or antibodies over an extended period of time, using the body’s normal functions to provide an environment that they can thrive in. The Bio-Spun™ Cell Chamber is composed of 3 layers (Figure 3). The inner layer is made of Bio-Spun™ material that provides ideal growth conditions for the encapsulated cells, the outer layer (also made of Bio-Spun™ material) prevents fibrosis and promotes the ingrowth of living tissue. Finally, a porous membrane between the two Bio-Spun™ layers allows for inflow of nutrients and outflow of therapeutic proteins produced by the cells while preventing the immune cells from entering the chamber and the encapsulated cells from leaving the chamber.


The Bio-Spun™ Cell Chamber can be constructed into 3 sizes depending on the end use (Figure 4A). For drug delivery testing in a rat’s brain, the Bio-Spun™ Cell Chamber was made into a 1.5cm diameter tubular construct (pictured on the left side of Figure 4A). For preclinical assessment, the dimensions are 1.5cm x 2.5cm (picture in the middle of figure 4A and figure 4B). Finally, the right side of figure 4A shows the Bio-Spun™ Cell Chamber size for clinical trials in humans which is 5cm x 8cm. All three sizes are made using the same method and are composed of the same materials.

Benchtop Development


To test how cells perform while inside the Bio-Spun™ Cell Chamber, we selected ARPE-19 cells that were modified to express a gene that allows produce of an enzyme that has a luminescent signal (Figure 5A) as well as a target drug that can be monitored using a benchtop test. This type of cells gives the scientist a visual representation of how the cells are doing in terms of viability. The higher their luminescence intensity, the higher the cell number, with luminescence being proportional to the cell number (Figure 5B).

This study showed that the Bio-Spun™ Cell Chamber could be successfully loaded with cells, with cells remaining alive within the chamber.



Preclinical Assessment


The next step was to evaluate a cell-loaded Bio-Spun™ cell chamber in a preclinical model. ARPE-19 cells used in the benchtop studies were loaded into Bio-Spun™ Cell Chambers. These chambers were then implanted into a subcutaneous nude mouse model. After implantation, the Bio-Spun™ Cell Chambers showed significant tissue integration with capillary formation and minimal fibrosis within 30 days (Figure 6A). Drug concentration in the mouse’s blood with Bio-Spun™ Cell Chamber implants, which was measured for over 120 days, had persistent drug release over time (Figure 6B).


Ongoing Development


Many successful in-house studies have been done on the Bio-Spun™ Cell Chamber to ensure the quality of the implant. More importantly, the Bio-Spun™ Cell Chamber has also been validated by other customers who have purchased the implant for their own applications that focus on liver disease, drug delivery and treating diabetes. Experiments that have been done by other companies show that the success of the Bio-Spun™ Cell Chamber is not dependent on the scientist handling the device or the types of cells that are loaded into the device. This is based on results showing different cell types maintaining viability and biotherapeutic production.


Next-Generation of Bio-Spun™ Cell Chamber


Next generation Bio-Spun™ Cell Chambers are already under development by the BioSurfaces team. This includes adding a resealable port to the Bio-Spun™ Cell Chamber to eliminate the need for equipment to seal the chambers after cell loading. This makes it easier for the scientist to load cells without the need to seal the top since the port will reseal on its own. Another iteration of the device has focused on increasing surface area inside the chamber to give the encapsulated cells more room to expand. This will be important because the greater the number of cells encapsulated inside the chamber, the more a targeted therapeutic can be released. BioSurfaces will continue to work internally as well as with customers on the development of this technology, with the goal of seeing this technology advance to helping patients treat their respective disease.


Written By:

Rayan Kassab

Director of Device Development




References

1 https://www.cdc.gov/chronicdisease/about/index.htm

2 https://cmcd.sph.umich.edu/about/about-chronic-disease/

3 https://careexcellence.org/blog/patient-compliance/

4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696292/




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