Importance of Selecting the Right Scaffold – Lessons from the Three Little Pigs
The title of this scientifically-focused Monthly spin may take some people by surprise. How would a children’s story relate to selecting the appropriate scaffold for use in benchtop and medical devices? I propose that they are more related than you think. In the Three Little Pigs, construction of their dwelling required selecting the right framework, materials and construction to weather outside forces (a.k.a. sheer wind forces from the big bad wolf). It took them three attempts at building the optimum house, learning from each failure to improve on the final version. Even in a simple children’s story, there is learning from history, looking to improve performance and trying not to repeat the same mistakes. The concept of selecting the right scaffold, one of the most important aspects in medical device and benchtop testing development, is constantly overlooked. I would argue that having the right scaffold can be an important key to success.
I was first introduced to the world of biomaterials over 30 years ago when I started working in the field of Vascular Surgery Research. While that seems like a long time ago, man-made (synthetic) materials being evaluated and used for medical implants (i.e. polyester, polyurethane, Teflon) goes back over 80 years, with naturally-occurring materials (i.e. silk, cotton) dating back centuries. Medical device technology has progressed over this time, but one area that continues to stay consistent is the polymers used to make these devices and the resulting structures they are made into (i.e. knit, weave, nonwoven, extrusion). Many of these polymers have been shown to be durable when implanted and can be formed into the precise structure required for repair or replacement of the target area. One major issue that continues to persist is that textile materials comprising these devices do not fully heal in the body, potentially resulting in complications such as clot formation, infection and unregulated tissue growth that can ultimately lead to device failure or reduced functionality. Even today, highly-engineered medical devices continue to use these same textile materials from 80 years ago, which would be like the three little pigs continuing to build houses of straw or sticks and expecting a different outcome.
After many years of personally looking to change the biologic response at the material/body interface and seeing minimal gains, I realized that we needed to look at it from how the cells see the world. For example, if you get a splinter (or sliver depending on where you are from), your body immediately moves to isolate it because it is a foreign invader. This walling-off process is called fibrosis or scar formation. Many in the medical device community view this process as “healing”, but it is not true healing, only the body’s attempt to put this invader aside to deal with it later.
The body’s cells do not grow near or into current materials, leaving behind a thick collagen layer (seen in purple staining) as shown with artificial arteries (Figure 1). The current fiber diameters are orders of magnitude wider than the structure the cells normally grow on. Adding the immune response to the foreign invader further compounds the issue. Even with suboptimal results, many engineers, cell biologists and biomedical researchers still believe that when designing new devices, using current scaffolds will work good enough and that the scaffold is not important. Many different pharmaceutical companies are developing various cells to treat different diseases but one thing they have in common is that they have no effective way to deliver them into the body due to fibrosis. Like having a fancy sports car without an engine.
Changing this paradigm was the reason that BioSurfaces was established. We believe the scaffold that the cells interact with needs to be similar in size and structural dimensions (randomized orientation) to what these cells would
normally encounter (Figure 2). The structure that the cells normally grow onto, called the extracellular matrix (ECM), is comprised of small, randomly-oriented fibers. Current textiles, such as the woven polyester shown, are much larger than those comprising the ECM. In contrast, fibers comprising our Bio-Spun™ scaffolds are closer to size and structure to ECM. Comparing materials made from polyester that have different fiber size and construction (knitted textile versus Bio-Spun™) in preclinical studies (Figure 3) showed that textile fibers
generate a significant immune response whereas the Bio-Spun™ fibers allow the cells to infiltrate and heal the material.
Another study we conducted reaffirmed this hypothesis was when we evaluated different components of our Bio-Spun™ Cell Chamber. In the chamber, we use a porous polyester film to prevent immune attack on the cells on the inside of the chamber while letting the target agents to release from inside the chamber. We implanted the polyester film alone and the film coated with our Bio-Spun™ polyester scaffold in a preclinical study. Same polyester polymer but in different configurations. The body’s reaction to each was very different (Figure 4). The immune system reacted strongly to the polyester film whereas the same film within our Bio-Spun™ polyester fibers showed excellent tissue healing and no response to the film. While we are showing examples related to
polyester materials, Bio-Spun™ scaffolds comprised of other nondegradable polymers such as polyurethane or biodegradable polymers such as PDLGA, PLLA or PGA behave in the same fashion.
This does not mean that existing textiles have no place in new medical devices. On the contrary, there are properties that textiles provide that cannot currently be provided by existing electrospun materials such as high mechanical strength for areas such as bone anchors or suture stays. This is where combining the healing properties of our Bio-Spun™ scaffold with strength of current textiles can provide a scaffold with desirable properties. BioSurfaces continues to work with various partners and customers to provide such combination materials as needed.
Based on the data provided in this article, I hope that you have an appreciation that selecting a scaffold is important for various medical devices and benchtop diagnostic applications, something that the three little pigs learned a long time ago.
By: Matthew D. Phaneuf
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