“I just want to say one word to you. Just one word,” said the businessman Mr. McGuire to Dustin Hoffman’s character Benjamin in The Graduate, who had recently completed his college education. That word, of course, was “plastics” and it was offered to Benjamin as a sort of career advice: plastics are going to be big. At the time the film was released in 1967, it would have been hard to foresee just how right Mr. McGuire would be. Plastics are literally all around us. They are often within us, too, in the form of everything from dental polymers to PEEK spinal implants.
|Peter Gabriele is director, emerging technology at Secant Medical.|
When it comes to the medical applications of synthetic materials like plastics, we may have just scratched the surface says Peter Gabriele, director, emerging technology at Secant Medical (Perkasie, PA). (Side note: The company will be exhibiting at MD&M West in Anaheim, CA from February 12–14.) “The designer of the material has the opportunity to integrate what is known about cell biology and material interaction with components,” Gabriele says. That serves to either antagonize or improve the wound healing process, he explains. “The more we know about the mechanism of healing, the better we can get at designing polymers that can accommodate the wound healing process.”
At the MedTech Cardio conference in Minneapolis, Gabriele spoke on this subject in a presentation titled “Getting to the Holy Grail: Intelligent Design for Small Bore Vascular Scaffolds.” Gabriele explained that basic constructs in synthetic textile repair could be transformed into biodegradable tissue scaffolds. “The impact of coupling new biomaterials with precision textile engineering allows the tissue engineer the ability to control multiple functional tissue mechanical properties of the biodegradable with ‘rational’ scaffold design.” Gabriele speaks at length on this topic in the following Q&A.
MPMN: What is “rational” scaffold design?
Gabriele: Rational scaffold design is the concept of maintaining a homeostatic environment through deliberate engineering and modification of materials to meet the requirements of cell biology. If you know certain trophic agents, growth agents or agents of cell biology are capable of eliciting a certain response by the tissue or cell, you’re making a smart scaffold. You’re designing the scaffold to accommodate the healing process.
Put some critical thought into how that structure or chemistry accommodates cell activity: the cell activity is what is important. It’s not important to put a synthetic material in the body and hope that the body accommodates the cell material; we have to accommodate the cell activity. In doing that, we can’t disrupt it; we can’t disrupt what has been a part of the cell’s development.
In the past, wound healing has been separated from regenerative medicine and tissue engineering. Wound healing tended to be relegated to anything topical or dermal. However, when you implant a device into the body, the body must go through a healing process. This is no different than what occurs during a dermal event. The body undergoes hemostatic inflammation, proliferation and remodeling. When a scaffold is implanted, the body undergoes these processes as well. The scaffold has to be in the wound space and accommodate the homeostasis of the tissue.
|This graphic illustrates some of the potential applications for next-gen synthetic materials.|
MPMN: Why could it be the "holy grail" for cardiovascular disease?
Gabriele: The holy grail is to reconstruct a synthetic bioresorbable small bore (less than 6 mm in diameter) vessel. The challenge is to provide performance in a mechanically dynamic environment while simultaneously regenerating vascular tissue within a degradable scaffold. We want to be able to build the bridge while also driving over it.
The reason rational design will be an important factor in getting to the holy grail is that we will have to design vascular systems that are compliant from a human body engineering standpoint while providing an opportunity for the healing process to occur as the body regenerates its own vascular replacement. By integrating materials that allow as close to normal functioning as possible, the healing process may restore original functionality that is as close as possible to the native tissue.
MPMN: What are the potential applications of natural extracellular matrix (ECM) and PGS?
Gabriele: Cardiovascular will be the predominant application of PGS, poly (glycerol-sebacate), due to its elastomeric characteristics (the heart is a mechanically dynamic tissue). PGS also has the potential in orthopedics, soft tissue repair and any replacement of the scaffolding structure where an elastomeric activity or behavior of material has to be temporarily provided to the healing condition. At Secant Medical we’ve already engaged in these emerging technologies and are actively conducting materials research through synthesis and analysis to address current industry needs in biomaterials development.
|Peter Gabriele summarizes his thoughts on the use of synthetic materials for cardiovascular applications.|
There is a limited selection of elastomeric bioresorbable materials available to engineering design. PGS has the closest simulation to the human tissue modulus. It can be designed to simulate the engineering radial compliance requirements of human tissue as well as the matrix design of the ECM. One of the advantages of PGS is that its degradation products are metabolites. Metabolites don’t antagonize the healing process as much as other synthetic biodegradables where acids are formed and a significant amount of biological activity must be expended to clean up the wound space. One of the benefits of having metabolite breakdown products is that by not flooding the wound space with acidic materials, a more normal ECM can be developed—one that is more balanced in elastic and collagen behavior. While the scaffold is being deconstructed by the human body, it’s not interfering with cell processes.
MPMN: I've heard a lot about bioresorbable implants and about their potential use in stents. What are your thoughts on that as well as other potential applications of bioresorbable materials.
Gabriele: The traction of bioresorbable materials in stents is that it allows for the restoration of original tissue functioning. In rigid stents or those that do not break down, the artery is left patent but cannot regain its original pulsatile activity. By allowing the artery to remain patent and at the same time slowly degrading the stent, the original function of the tissue can hopefully be restored.
In general, when you find a bioresorbable material that can be engineered into other applications, it becomes exciting, because you have new solutions to old problems. The history of bioresorbables started with resorbable sutures. Those materials were only available because they had a history of use in the human body. They migrated into something other than the suture and into structural components. The consequence of their degradation and the role they play in the wound space is only recently being understood. Part of this is because there’s been very little profiling of the dynamics of the biochemistry of wounds. There’s a shift in PH and there’s a shift in composition of enzymes during the healing process. It’s not a static event; it’s an event that must be managed. The body manages it very well, but if you’re not aware of what the body has to accommodate, then the wound doesn’t heal normally. By understanding bioresorbable chemistry and the interaction with the human body, we have a better chance of getting to that homeostatic state.
To achieve true tissue regeneration, we have to create materials that balance themselves with the body’s natural functions. By making a broader audience aware of the depth of the bioengineering that goes into creating these materials, we are on our way to a much safer development of implant materials for the future.
MPMN: Which synthetic materials do you think have the most promise for orthopedic applications?
Gabriele: This is difficult question to answer, because one of the things that we’re learning about tissue regeneration is that the local environment of the tissue plays an incredible role in the healing process. There is not one shoe that fits all material. To think that one material will be the solution for all applications is a bit naïve.
MPMN: Is there anything I didn't ask about in the above four questions that would be of special interest to medical device engineers who work with implants?
“Keep in mind that the history of bioresorbable implant devices is still quite young.”
Gabriele: One of the messages I want to emphasize is that we must be more mechanistically oriented in the design of products, which takes us back to the concept of rational design. There are not only the events that occur as a result of polymer degradation in the strict sense of the chemistry of the polymer, but there is also chemistry of the wound and chemistry of the healing site that has to be understood. It’s only when these two understandings converge that we can begin to make more sense out of what is needed. The only way to do that is to understand the mechanism of the chemical breakdown, healing and interaction of engineering materials with the human body, as well as processing them and making sure that we don’t introduce some stray contaminant that becomes antagonistic and disrupts the healing process.
The future rests on the concept of biodesign. When something is biodesigned, it addresses a criteria of everything from materials interaction with the body, compliance laws, and engineering limitations with respect to human physiology. It’s a pretty hot topic right now.
Keep in mind that the history of bioresorbable implant devices is still quite young. We’re still learning a lot about tissue engineering, tissue regeneration, materials science and materials interaction with the body. With progress that’s been made, we’ll be able to start designing materials for the future. Key to this is the idea of metabolic breakdown products: creating bioresorbable materials where the body can handle the breakdown products safely as opposed to being contaminants.
- Five Mistakes That Can Derail Your Product Development Effort - Webcast
- How to Manage Risk Throughout Medical Device Product Development Cycle and Beyond - Webcast
- Common Mistakes to Avoid During Medical Device Product Development - Webcast
- BIOMED Boston - Event
- MD&M West - Event
- Build (or Fix) Your Quality Management System - Webcast