The Business of Biofabrication

A dynamic that is of interest to all of us is the ability to accelerate the integration and adoption of bioprinting into our healthcare workflows. We’ve seen with companies like Dimension Inx, or Cerhum who are making progress in the industry. They have been using chemistries that have come before and been approved by the FDA. This is important again because we are taking a stepwise approach to build off known innovation. In the case of bioprinting, we are adding in the ability to pattern these chemistries so that there is a micro or macro architectural benefit to a therapy that is provided. I’m taking advantage here as well to broaden the definition of bioprinting from solely printing cells and biomaterials together, to a classification to also include printing biomaterials without cells yet these materials play a rejuvenate role. 

To think about this further let’s look at 2 cases where the microarchitecture is playing role then expand on 2 areas where the macro architectures is playing a role.

Micro Architectures

A strategy in 3D printing for production that has become quite known, is the ability for engineers to take advantage of different lattice structures for a different part performance. A hexagonal infill can make a part have a different stiffness from a straight lattice infill. The number of geometrical variances on infill is a big area of study and will only to continue to grow in complexity as the ease of creating part specific patterns grow. On the same line, an 80% infill can have a different variance of weight vs strength performance than a 20% infill. These design options of 3D printing are adding a lot of value to applications in aerospace, aeronautics, and automotive where weight has a big effect on performance. So parts are not only lighter, yet potentially stronger too with the right infill geometry. 

As we think about how this plays a role in bioprinting, there are two very clear value add areas where microarchitecture comes to mind:

1. Cell migration and growth infill

The ability to be able to space lattice or infill geometries in certain ways can lead to different cell migration and growth infill patterns. This is an interesting one that I believe became most clearly seen with Dimension Inx. Traditionally speaking and even still quite popularly today, surgeons take bone cement for example, or paste and try to shape it into areas where bone potentially needs to grow. Consider once this is placed, it’s a solid block that the cells need to remodel and grow into. This for example is a common practice in CMF surgeries where surgeons will take hydroxyapatite and apply where needed whether through injection or within an implant to help promote bone regrowth. In contrast, Dimension Inx for example has understood that by making 3D printed lattice sheets, cell can have an easier path to grow on and increase the rate of bone regeneration. This idea can also similarly be seen in knee and hip joint implants that use 3D printed titanium. They print implants with lattice configurations, each company with its own special design, that provide areas for bone to grow into the implant securing it in place. In both of these cases Dimension Inx and joint implants, neither has patient specificity. There is no mass customization play. Yet, a ton of value is added because of the increase regeneration rate. The bottom line here is there is no other way to make the lattice geometries other than using 3D printing. The beautiful thing here is that the lattice design takes into consideration cellular behavior and creates a predicated path for them to grow into, migrate, and ultimately help the patients further.

2. Controlled degradation rates.

As we’ve seen, lattice geometries can play a role in part geometry in strength and cellular infiltration. Another area where the internal lattice geometry can play a role is in degradation rate. In many instances, as bioengineers, we are interested in restoring the body to its natural state or form and ultimately allow the body to continue to take on healing after it has been helped along. For example, in stiches! A simple example, think of a skin suture. It usefully keeps two sides of the skin next to each so they can work to fuse together again, rather than having to develop scar tissue in between. The technology of today allows surgeons though to repair and know the suture will dissolve away inside the body as well. Stiches have been one of the best tools surgeons can use to repair skin, organs, ligaments, vessels, and more. For example, surgeons can fuse a vessel they would like to redirect flow with. Using the suture, the cells will then rebound given the new connection and the suture will overtime dissolve away depending on how the degradation rate designed in the material.

Now given that knowledge in sutures, with 3D printing the degradation rate which is dependent on surface area can be taken a step further. Exposed areas degrade given their interaction with oxygen and water molecules. Point being, a lattice cube will degrade faster than a solid cube given there is so much more surface area exposed on a lattice than on a cube. This allows bioengineers to think about designing macrostructures with degradation control given their microarchitecture. Infills with less surface area will degrade slower, while those with more surface area will degrade faster. This can play a role by having certain areas of a part degrade faster than others. For example, imagine you know that a more damaged portion of the muscle needs greater support and greater infill than another area that is less damaged and needs less support. So, one can design a big custom mesh with different areas of infills to help the patients best.

Macro Architectures

With the above in mind, let’s explore the macro. We think of being able to 3D bioprint parts that have a patient specific fit or form. A few examples, to name a few, a 3D printed jaw, a custom specific joint implant, or patient specific airway stent. These are all examples where regardless of the microarchitecture, the outside form of the part being patient specific, could help improve the patient overall well-being. It’s interesting because in today’s world, the microarchitecture benefit has greatly out surpassed the macro architecture value. The specific reason is tremendous value has been achieved using unique lattice-based geometries for increasing the bone ingrowth rates on total knee or hip replacements, all while using standard sizes.

The important thing to consider is that no patient data is needed for the microarchitecture to be produced. These implant structures with latticed based geometries are produced using metal 3D printers and are produced in a range of standard sizes. When patient data is involved, it needs to travel from the patient to a medical device manufacture. And this is actually one of the biggest pieces of unbuilt infrastructure that is needed to further make patient specific implants a continuous reality. The standardization of the highways of this information would lead to a greater ability to be able to seamless deliver a patient matched implant.

Apart from that challenge, the value derived comes from the macro in the forms below.

1. Aesthetic Form

It’s no question that there is a function in an implant, the strength it has to undergo, the infill ratio it has to have, or the part’s tolerance. Yet, certain implants also have to have a specific, unique form. One of the easiest areas to see this would be in facial reconstructive surgery. Where symmetry and size play a tremendous role in the overall well being of a patient. For example, the same size ear on one to another, the size of a nose, or the integrity of the chin. All these have aspect ratios that play an aesthetic role on a patient’s self-appearance and, therefore, have a profound emotional consequence. A recent great example of this is in Cerhum most recent paper. They demonstrate how using specific 3D printing, facial surgery can be planned before hand and applied to the patient to achieve specific outcomes. This is in contrast to a surgeon needing to use cartilage or other materials to reconstruct or shape a patients while operating. Such technology allows for facial surgery to transform from more of an art to a science. This example is in bone alone, yet the application has the potential to be achieved in cartilage and vascular reconstruction as well. The use case would not be as beneficial in soft tissue, as internal organs, since theoretically soft organs can come in a host of different predetermined sizes to achieve a specific biologic performance outcomes, just as joint implants.

2. Spatial Form

To continue, spatial fillings can also have a tremendous effect on the performance of the part. This is the idea where the fit or the make of the part can have a direct effect on the functional performance of that implant. This is already seen in many custom facial titanium implants today. For example, a custom-tailored titanium implant for the jaw that fits snug into the defect is important to have the correct forces transfer in the jaw. Likewise, having the right cranial plate to create the right amount of cranial pressure is key to have the right fit. So spatial fit that specifically custom to the patient can have a direct role on the patient’s performance outcome.  This is common on cancer bone resections, where the tumor needs to be resected away and natural bone will also be resected away. These bone tumors can happen really in any bone in the body and titanium implants will be designed to fit in the exact match the way the bone was resected. While advanced chemistries that enable regeneration have yet to see this domain of value, one the clearest examples of today is from 3D Systems who is printing cranial plates with Evonik’s Peek material. And we can be certain that bioprinting will take advantage of macroarchitectural fit in the future.

Conclusion

The value that 3D bioprinting, particularly 3D printing with acellular advanced chemistries, using value add methods like micro- and macro- architectures are beginning to create real world value for today’s patients. By building off of these architectural design methods for implants we can focus on areas where innovation really counts, like novel chemistries and further understanding of cellular inclusion in the implants. We will continue to see these advance chemistries find their way further and further into our healthcare workflows and with great reason given their significant additional value. On a future article, we can explore what are some of these advanced chemistries and how each is presenting an opportunity for innovation.