Issue: December 2021
Source: Healio Interviews
Disclosures: Rodeo reports having stock options in Ortho RTI. Badylak, Farr, Fortier and Schlegel report no relevant financial disclosures.
December 16, 2021
10 min read
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Synthetics hold promise as soft tissue alternative

Issue: December 2021
Source: Healio Interviews
Disclosures: Rodeo reports having stock options in Ortho RTI. Badylak, Farr, Fortier and Schlegel report no relevant financial disclosures.
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Synthetic implants have been used in a variety of orthopedic procedures, initially replacing the parts of the skeletal system before being put into service to replace soft tissues, according to sources who spoke with Orthopedics Today.

Although generations of synthetic soft tissue implants have undergone research and development in the past 20 years, sources said more research is needed to improve on the outcomes of historical and current implants.

Lisa A. Fortier, DVM, PhD, DACVS
Lisa A. Fortier, DVM, PhD, DACVS, said 3D printing may improve synthetic soft tissue implants because it allows these to be custom-made specifically to fit the size and personal pathology of a patient. In addition, growth factors or cells can readily be added to 3D-printed soft tissue constructs to enhance repair.

Source: Platinum Performance Inc.

“There were carbon fiber grafts, for example, that were tried for anterior cruciate ligament replacement, and they had all sorts of problems. There were [polytetrafluoroethylene] PTFE grafts that have been tried for tendon, ligament and even meniscal replacement, and they are no longer on the market because they had such a miserable success rate,” Stephen F. Badylak, DVM, PhD, MD, of the department of surgery at the University of Pittsburgh, told Orthopedics Today.

Badylak said the primary reason for surgeons to use a synthetic soft tissue implant is to provide mechanical strength to the area of the body where the natural soft tissue has failed. When choosing a synthetic implant for orthopedic soft tissue applications, surgeons typically prefer a synthetic material that is degradable. According to Badylak, non-degradable materials often elicit a foreign body response that includes dense scar. To reduce this foreign body response in non-degradable synthetic materials, he said significant research has been conducted in the area of immunobiology biomaterials.

“In other words, we take a synthetic material that we know would elicit a less than desirable foreign body response, [and] attempt to coat it with a substance that can modify the way the immune system sees it and reacts to it, thus providing a better outcome for the patient,” Badylak said. “We preserve the advantage provided by a synthetic material but, hopefully, mitigate the scar tissue formation.”

Need for durability, elasticity

A concern with the use of degradable synthetic soft tissue implants is the risk of them rapidly losing mechanical strength and failing over time, Badylak said.

Stephen F. Badylak, DVM, PhD, MD
Stephen F. Badylak

“So, one favorable solution is a material that slowly degrades, is gradually replaced by host tissue with site-appropriate mechanical properties and eventually the original synthetic material is totally gone,” Badylak said.

Even if a synthetic material provides the strength and structure needed to replace the native tissue, he said most synthetic materials do not have the same amount of elasticity as the native tendons and ligaments.

“At the end of the day, none of [the synthetic implants] are a match for the native tissue,” Badylak said. “It is one of the reasons that this is still such an active area because there is nothing in the way of a synthetic soft tissue implant in orthopedics that comes close to matching the native tissue.”

Off-the-shelf solution

Despite the modest and variable results associated with orthopedic synthetic soft tissue implants, Scott A. Rodeo, MD, sports medicine surgeon, vice chair of orthopedic research and co-director of the Orthopedic Soft Tissue Research program at Hospital for Special Surgery, said they have the potential to provide an off-the-shelf solution for replacing lost tissue without having to use allograft, which has issues regarding cost, size and immune response.

Synthetic soft tissue implants also have a long shelf-life and provide faster implant availability to surgeons, according to Lisa A. Fortier, DVM, PhD, DACVS, editor in chief of the American Veterinary Medical Association and an Orthopedics Today Editorial Board Member. She said synthetic implants also reduce the risk of disease transmission found with the use of allograft tissue and reduce the risk of morbidity associated with autograft.

“Just having something off the shelf could avoid all of those issues,” Fortier told Orthopedics Today. “If it does integrate, it can mimic normal tissue and then [the patient] regains function.”

Although Badylak said synthetic soft tissue implants have the advantage of manufacturing reproducibility, Fortier said many synthetic soft tissue implants are manufactured in a few sizes, which may not work in areas where cartilage thickness differs between and within the joint.

“That can be a disadvantage vs. if you are going to do an autograft, you can sometimes pick from an area that you know is more homologous in tissue thickness and tissue mechanics,” she said.

Economic impact

Use of synthetic soft tissue implants may have a positive economic impact, as well.

Theodore F. Schlegel, MD
Theodore F. Schlegel

Theodore F. Schlegel, MD, senior vice president, clinical excellence, American Orthopedic Partners, said that although using a scaffold to preserve the native tissue in a large or massive rotator cuff tear may be costly, it is less costly than performing a reverse total shoulder arthroplasty if the tendon does not heal through traditional treatment methods.

“Scaffolds have often had a bad rap because they can be expensive, but if you are using them in the correct way ... economically, it makes a lot of sense because the implant has the potential to enhance healing and to preserve the patient’s own native tissue, which should be the goal, if at all possible,” Schlegel, associate professor emeritus in the department of orthopedics at the University of Colorado School of Medicine, told Orthopedics Today.

Synthetic soft tissue implants may have an economic value by restoring patient function and decreasing pain and morbidity, Fortier said.

“If you can resurface a big toe or a thumb or an ankle and get that patient off of nonsteroidals and physical therapy, you improve their life, not only through decreased morbidity, but also by freeing them from the time and expenses associated with supportive therapies,” she said.

However, even if synthetic soft tissue implants provide an economic advantage, Rodeo said many insurance companies see these as experimental due to the mixed and modest outcomes reported with these options.

Scott A. Rodeo, MD
Scott A. Rodeo

“If you could demonstrate that [synthetic soft tissue implants have] potential, especially in young patients, in replacing lost tissue and thus preventing ongoing issues and delaying things like knee replacement, then it can be economically advantageous,” Rodeo, who is an Orthopedics Today Editorial Board Member, said. “The challenge lies in identifying materials that are effective enough to be cost-effective.”

Hybrid soft tissue implants

With the amount of activity underway in the research into and use of synthetic soft tissue implants in orthopedics, sources who spoke with Orthopedics Today said they believe these types of implants will be around for the long-term. However, sources also said that the research in this area may be more focused on implants that combine synthetics with biologics than on synthetics alone.

“The hybrid devices are a good compromise for the people who want the mechanical advantages of the synthetic materials and the biologic advantages of the biologic materials,” Badylak said.

Although biologic materials take advantage of the naturally occurring processes that are present in building tissues during development and in repairing tissues while avoiding the undesirable immune response, biologic materials lack the mechanical properties that synthetic materials have, he said.

“It is a clear distinction between the two and that is why I think the hybrid [materials] are probably going to be receiving increasing attention in the coming years,” Badylak said.

More research needed

Rodeo said more research is needed to provide better understanding of the biology of the materials used in hybrid soft tissue implants, including how the cells interact with the synthetic material, whether the cells proliferate and how the cells can be stimulated to produce new matrix and new proteins.

“Another big area would be how can we implant these synthetic materials with exogenous cells. Could we take some stem cell or progenitor cell population outside the body and apply that to these materials and then apply the material?” Rodeo told Orthopedics Today. “That has exciting potential because we put these materials in the body [and] we rely on the body’s own host cells to infiltrate the material. There is a lot we do not know about the cell types that infiltrate the material, how those cells interact with the material. Those are important areas.”

It is also important to understand more about the biomechanics of synthetic and hybrid soft tissue implants, such as the material properties and strength at implantation, as well as over time, Rodeo said.

“Many of these materials are ideally resorbable over time and while they are replaced by new tissue as they resorb, they lose strength. If they are going to lose strength, you need that load to be transferred to newly forming tissues,” Rodeo said. “We need to know more about the biomechanical characteristics of these materials: their material properties, their strength, their stiffness and how they lose strength and stiffness over time as they resorb.”

Similar to the current synthetic soft tissue implants, Badylak said that future research into hybrid soft tissue implants will also have to show that these are cost-effective.

“That data only comes with time,” Badylak said. “It is a hurdle in today’s reimbursement world, but you can overcome it if you are persistent enough and have enough money to get through the clinical studies.”

Tissue engineering

Researchers are also focusing on tissue-engineered structures that would allow cells within a synthetic material to produce new tissue, according to Schlegel.

“What we are ultimately striving for is to create a new soft tissue implant that could provide mechanical strength of the synthetic structure and then be able to infuse it with proteins, growth factors or a number of proprietary chemicals that could create a positive healing environment while still having the same stiffness of the tendon or the tissue that you are trying to heal,” Schlegel said.

Graphic showing 10-point imporvement in pain scores among patients treated with synthetic meniscal implants

At Colorado State University, Schlegel and colleagues are researching an “instructive scaffold” that creates a mechanical environment that allows cells to grow, replicate and create new cells and tissues that can be customized for any environment.

“We can actually now [3D] print collagen, which is a natural constituent of a native tendon, and we can mix and control that with some other biomaterial,” Schlegel said. “Maybe we can get some of the structural strength, but then also include a natural compound or constituent to the tendon in a way that would create strength and, at the same time, induce a cellular response.”

Despite still being studied in a laboratory setting, Schlegel said he is optimistic about this area of research.

“I would say I am optimistic that this will become an emerging field and will allow a solution to a lot of the problems we have today,” Schlegel said.

Use of 3D printing

Another way synthetic soft tissue implants may be improved is through the use of 3D printing, which can lead to custom-made implants for patients, according to Fortier.

“3D printing has been happening for a long time and today you can weave in growth factors, tissue-specific cells or mesenchymal stem cells; basically, whatever you want to combine,” Fortier said. “The more complicated it becomes, the harder it will be to gain regulatory approval, but the biggest advantage of 3D printing would be the ability to custom-make the tissue to the exact size and shape needed for an individual patient, not in just generic small, medium, large, extra-large sizes.”

When looking at specific soft tissues, Fortier said instrumentation and integration of cartilage and bone with host tissue can be one of the trickiest problems in osteochondral areas. She also said the biggest hurdle in using synthetic soft tissue implants in the meniscus is replicating the native attachment for a full meniscus.

“We are doing OK with replacing part of [the meniscus], but the integration of any implant with the host tissue is still lagging,” Fortier said. “For the full meniscus, the attachment to the tibial surface is problematic, particularly in the back of the joint.”

Synthetic, durable replacement

One synthetic implant currently under review by the FDA that would replace the full meniscus is the NUsurface medial meniscus implant (Active Implants LLC), according to Jack Farr II, MD, professor of orthopedic surgery at Indiana University School of Medicine, OrthoIndy and OrthoIndy Hospital. Results presented at the American Orthopaedic Society for Sports Medicine and Arthroscopy Association of North America Combined Meeting showed patients treated in a 2-year randomized controlled trial with the synthetic meniscal implant experienced superior improvement vs. non-surgical controls in the KOOS pain and KOOS overall scores.

Jack Farr II, MD
Jack Farr II

“The NUsurface [has] been in Europe for 9 or 10 years and some of those devices are still functioning,” Farr told Orthopedics Today. “So, that is getting a synthetic meniscus to the point of meniscus transplant durability.”

As researchers come close to identifying a synthetic soft tissue implant that works, Farr said it is important for current and future products to have intermediate- and long-term post-market studies.

“We do have multiple products in the pipelines, many of them appear promising and we just need to be objective and follow them in the intermediate- and longer-term to see where they fit,” Farr said.

Understand the basic science

When implementing synthetic soft tissue implants into practice, Schlegel said surgeons should understand the basic science and application of the implant, how the technology works, its limitations and consider whether a patient would benefit more from an implant or scaffold. Having a better understanding of synthetic soft tissue implants and their applications may help decrease failures, which Farr said may not always be due to the implant itself, but be caused by the environment or incorrect surgical indication.

“You have to know and follow proper indications, and place it into an environment that will give it an opportunity to succeed. You do not want to have the ‘writing on the wall’ before you start,” Farr said.

Fortier said surgeons should be vigilant in watching for rejection or signs of it and be careful extrapolating a synthetic soft tissue implant from one joint to another.

“Something that might work in the knee might not work in the ankle and vice versa or might not work in the toe,” she said.

Even having a positive outlook regarding the future of synthetic soft tissue implants in orthopedic surgery, it is important for surgeons to look at the history of these products and find the commonalities in failure modes and how to prevent them in the future, according to Farr. As new synthetic products continue to be studied and released, he said surgeons should review the pre-clinical and clinical literature, the FDA indications for the product, the durability, as well as failure mechanisms and the salvage for a failure.

“This is not over. Synthetics are not done; biologics are not done. There are still improvements. There are still new products ... in the pipeline for synthetics,” Farr said. “Researchers and companies alike are both still pursuing synthetics and biologics hand-in-hand and some companies are pursuing both. ... [W]e are in the early innings of this long ballgame.”

Click here to read the Point/Counter to this Cover Story.