The Advantages of Biodegradable TPUs in Medical Applications

Biodegradable thermoplastic polyurethanes (TPUs) are currently not widely used to repair human tissue, but Andre Martinez makes a reasoned case for taking them into consideration in certain applications. A senior scientist at DSM Biomedical, Martinez will explain the advantages of TPUs in such applications during a panel discussion on innovations in resins, surface modifications, and processing at the forthcoming MiniTec conference presented by the Society of Plastics Engineers (SPE). He graciously took time to share some insights with PlasticsToday ahead of the conference, part of Informa Markets Engineering West in Anaheim, CA, that includes co-locates Medical Design & Manufacturing (MD&M) West and Plastec West. The event comes to the Anaheim Convention Center on Feb. 6 to 8, 2024; MiniTec starts a day early, on Feb. 5, at the same location. 

I would like to begin by asking you to explain the difference between biodegradable and bioresorbable, terms that are sometimes used interchangeably. 

Andre Martinez: Let’s first limit both terms to their use in the medical field, so we’re not talking about materials that may be degradable by certain bacteria or fungi, or that degrade over long periods of time in a landfill aided by biological action.

Biodegradable materials can be broken down in the physiological environment into fragment components through some combination of the hydrolytic environment, enzymatic action, pH, or oxidation via immune response. In practical terms, we think of materials that can be substantially degraded in a clinically relevant amount of time — months to years, but not decades —  as being biodegradable.

Bioresorbable is an additional layer on that definition. To be resorbable, the breakdown products must be taken up by the body and integrated into cells or tissue or eliminated from the body. So, if I made a polyurethane with a polyester polyol, it would likely be biodegradable, but if the degradation products couldn’t be eliminated or used by the body, then it wouldn’t be resorbable.

To complicate matters, if I made a multi-block polyurethane using polyester and PDMS polyols, it might be biodegradable and partially bioresorbable.

One last layer of confusion: The terms resorbable and absorbable seem to be used interchangeably but you may be able to make a distinction based on whether the material can be fully integrated into the body or part of the material cannot and is eliminated. Just don’t ask me which is which!

I won’t, Andre. But let me ask you this: What are the clinical benefits of using a biodegradable material and, within that scenario, what are the advantages of TPUs over other polymers?

Andre Martinez: Biodegradables are preferred when there is a clinical benefit to having that medical device disappear at some point. Many of us have non-degradable plates, screws, and meshes in our bodies that enable or augment tissue repair, and they work great in many applications. But take the case of a child or adolescent. They are not done growing, so permanent structural implants can be a detriment to their development. Imagine repairing a bone void with a permanent material that integrates with the natural tissue but then that bone grows another couple of inches, potentially in conflict with the mechanical forces of the foreign permanent material.

Other benefits applicable to anyone are that a biodegradable material will not cause trouble years later by becoming displaced, causing infection or irritation, or failing in a variety of ways that may be related to unintended long-term degradation. Additionally, if any surgical revisions are required, permanent implants may need to be removed or worked around, thus, complicating procedures. If we can help it, we prefer to allow the body to regenerate its tissue fully, with no residual augmentation. The resulting tissue can then maintain itself through the continual renewal processes our bodies go through.

Other polymers are used currently in tissue repair applications. Polyesters such as PLA, PLGA, PGA, PCL, and their copolymers with hydrophilics are commonly studied for these applications in academia and some are employed in approved devices. TPUs can exist as a parallel option, and in some cases have advantages. In fact, biodegradable TPUs are often substantially composed of those same polyesters as polyols and so take on similar degradable characteristics.

Beyond that, the mechanical properties of TPUs can be tailored to be similar to — or vastly different from — degradable polyesters, which are generally very rigid. TPUs can be made to be very flexible, which can better enable the repair of soft tissue.

Take, for example, the application of wound repair. The scaffold that allows skin to grow into it should be able to flex with the tissue until it eventually is degraded and reabsorbed. Unlike common biodegradable polyesters, TPUs are generally elastomeric in the sense that they can be stretched and return to their initial dimension without permanent deformation. While other elastomeric biodegradable polymers are available, these are generally cross-linked and cannot be reprocessed once synthesized. TPUs achieve their elastomeric nature without cross linking, which allows device manufacturers a high degree of flexibility in producing parts from TPU pellets via melt or solution-based techniques.

How commonly used are biodegradable TPUs in clinical practice? 

Andre Martinez: It’s actually quite rare compared with the aforementioned polyesters for several reasons.

First, introducing new implantable materials is always a challenge in the medical field, and the tendency is to make devices using the most established materials to increase the probability of getting 510(k) approval from FDA. The biodegradable TPU devices that are on the market are using PCL, PLA, and hydrophilics like PEG as polyols for this reason, because we know they are biocompatible, function well, and can get approved.

Second, in many cases the aforementioned polyesters are more appropriate. The mechanical properties of PLA and PLGA lend themselves well to interfacing with hard tissue, such as in suture anchors, or as a component of a bioceramic for bone repair.

Third, there is a question of biocompatibility in some formulations. Most industrial TPUs are made using aromatic diisocyanates, which may generate carcinogenic products if they degrade, so they cannot be translated into biodegradable formulations. Aliphatic diisocyanates react at slower rates and may require catalysts to be used in the same manufacturing processes. This presents a challenge of choosing formulations and manufacturing techniques that yield biocompatible material while being efficient.

Finally, biodegradable TPUs compete with biologically derived materials for repair of soft tissue. These may be constituted of processed collagen for non-load-bearing applications, or autografts, allografts, or xenografts when load-bearing mechanical properties are needed. Where applicable, these natural materials are currently the best option for the patient.

However, using synthetic materials such as TPUs has the promise of being much cheaper, more efficient to produce, and with less concern of causing infection. The use of synthetics reduces the need for surgeries to harvest autografts, is not reliant on cadaver availability, and is kinder to animals. The expansion of biodegradable TPUs in tissue repair depends on demonstrating similar performance to natural materials in soft tissue applications to the point that their gap in performance is surpassed by the benefits of using synthetic materials. Several biodegradable TPU products are currently in commercial use for wound repair, tendon and ligament reconstruction, and meniscal repair, so we are headed in that direction.

What is DSM doing to advance this technology?

Andre Martinez: Academia has shown the potential for biodegradable TPUs in tissue repair. DSM Biomedical has the TPU manufacturing ability, industry knowledge, and quality framework needed to make these materials available to the industry. Additionally, our expertise in natural materials that may be used for similar applications is a synergy both in know-how and the ability to consider combination products.

In our wider medical-grade TPU business, our strategy has not been to sell finished devices. We act as a total solutions provider for our customers, tailoring materials specific to their needs and providing technical service at each stage of development. While we are at the preliminary stage of optimizing biodegradable TPU formulations for applications where we see the best value, we will look to partner with final device manufacturers to bring devices to market.

Martinez will discuss the use of biodegradable TPUs for tissue repair at the session titled, "Materials: Innovations in Resins, Surface Modifications, and Processing," on Feb. 5 at 8 a.m. It is part of the MiniTec conference track at the Anaheim Convention Center. The other speakers at that session are DSM colleague Jing Liu, who heads the US R&D Center, and Fred Birkel, engineer at Avient Corp. Ned LeMaster, application development engineer at Delrin, is scheduled to moderate.