CHANGING THE FUTURE OF BREAST RECONSTRUCTION: UNDERSTANDING SCAFFOLD TECHNOLOGY

Breast reconstruction has evolved considerably, with new techniques and technologies continuing to expand the options available to patients. In this episode, we sit down with Dr Michael Wagels to explore the use of scaffolds in breast reconstruction and the clinical trials investigating their role.

In breast reconstruction, a scaffold is a special mesh-like structure that helps support and shape a new breast after surgery. It acts like a framework, providing support for breast tissue or an implant and helping the breast maintain a natural shape. Some scaffolds are made from materials that gradually dissolve as the body’s own tissue grows around them, while others are designed to remain in place. Scaffolds can help surgeons achieve a more natural-looking result and may offer new options for women undergoing breast reconstruction following breast cancer surgery.

Dr Wagels explains how scaffolds can be used in reconstructive surgery, what the evidence tells us so far, and how ongoing research could help improve breast reconstruction in the future.

“As a plastic and reconstructive surgeon, I am involved in working with patients who are dealing with very complex problems. And really, it’s at the pointy end of a complex problem where one has to think outside the box, so to speak, and come up with innovative solutions, which then one hopes can actually create a bit of a paradigm shift across some of the ways that we currently do things in a breast context.”

“What that means is that, for a long time now, we’ve been using silicone breast prostheses, and they have been causing significant problems for a significant period of time. And there’s been a real reticence to move away from them logically because of their commercial viability, which is not a good reason to persist with something. So, I’ve been very interested in trying to change that using biofabrication-type techniques.”

Your presentation is focusing on the use of scaffolds in breast reconstruction. What are scaffolds and what role do they play in breast reconstruction?

“Scaffolds play a very important role in biofabrication, broadly speaking, so this might apply to any context. It’s not specifically in the context of the breast, and I also work in other body parts. I’ve run clinical trials of biofabricated solutions which employ scaffolding parts in the craniofacial skeleton and in low-bearing long bones, again where there’s some challenging problems that were presented clinically.”

“If we think about biofabrication and tissue engineering as a concept, what’s required are a few key elements to be able to create tissue out of seemingly nothing. One of those is to have some sort of supporting structure, and that’s the job of the scaffold.”

“The second is to have a cellular element that has some sort of regenerative potential. So, we need cells that can grow and turn over. We need blood supply to keep everything alive, which is where a lot of tissue engineering falls down, certainly when it gets scaled up.”

“And we also need the right mix of growth factors, and they may be growth promoters and growth inhibitors, just to keep the balance of the tissue regeneration right. So really the role of the scaffolding, which is referred to as the diamond concept of tissue engineering, the scaffold provides the mechanical support to help the tissues resist the natural forces that arise within the body, and also to help direct the growth of the regenerated tissue so that it assumes roughly the correct shape and the correct proportions that we’re after.”

And so, like many surgical innovations, the use of scaffolds has continued to evolve as more evidence becomes available. What have we learnt so far and what questions are researchers still working to answer in this space?

“What we’ve proven so far is the scaffolds, when we confine the use of them to materials that we know have a good track record for implantation, we know they’re safe and we know that they’re well tolerated.”

“When you confine the materials to things that are known to be safe and well tolerated, you’re dealing with a fairly narrow band of materials that are available in the vast world of material science, which is a whole specialty unto itself.”

“When we use them in the way that we use them for the breast, we know that they’re safe and well tolerated, which is good. The problem is when we try to scale up the use of the scaffold and of course we need to introduce a biological element, so we actually inject a patient’s own fat into the scaffold to then create the replacement volume that’s required for breast replacement.”

“When we try to scale up to large volumes, the kinds of volumes that might be required for breast reconstruction after mastectomy, for example, we find that the quality of the regenerated fat is just not as good, particularly in the central part of the scaffold. We’ve demonstrated that in animal studies, but we haven’t been that adventurous in human studies.”

“So, there’s a bit of work for us to do to understand how we can improve on the regeneration of the fat, certainly in the central part of the scaffold. That’s likely going to be, if we come back to the diamond concept, making improvements in each part of the diamond concept.”

“So, we probably need a better scaffold, one that’s going to provide a little bit more mechanical support than it currently does and provide support in a way that’s dynamic.

“Material science has to find a better product for us to use. We need to improve the vascularisation of the scaffold, and there are ways that we’re exploring how to do that.”

“For example, we are looking at various extracellular matrix factors. These are things that live outside the cells or between the cells that are known to promote the growth of new blood vessels.”

“And we’re looking specifically for factors that we can introduce to the scaffold. So, the scaffold becomes a delivery for that particular therapeutic agent. And while we’re doing that, we’re also particularly interested in being contributors to survival of the disease and offering opportunities to deliver therapeutics that have a survival benefit.”

“That’s chemotherapeutic agents, essentially, that could be incorporated into the breast scaffold. That’s years away, but we recognise that the scaffold in its current guise is not perfect and it’s not going to fulfil all of what we need a device like that to do.”

Why are clinical trials so important in this space?

“For the same reason they’re important in any space. It’s really a progression of knowledge. And I’m pleased to hear you use the plural clinical trials because a single clinical trial, certainly at phase one, doesn’t really prove anything other than safety and tolerability, and we know it’s safe.”

“As I mentioned, from the clinical trials we’ve done to date, we don’t really know how efficacious it is. And so, we need to move to phase two and phase three trials. These trials are essential because it’s unethical to administer a treatment to a patient that’s unproven, and there are mechanisms in place to prevent that from happening.”

“For example, we can’t support the free market availability of the device, certainly not in Australia, until it is listed on the Australian Register of Therapeutic Goods. And a certain amount of evidence needs to be generated to demonstrate not just safety, or intolerability, but efficacy in order for that to happen.”

“Australia is a very safe place to be having medical devices implanted. It’s also a very safe place for us to be generating the evidence to support that. And so the trials we’ve been involved in today have been sponsored clinical trials, and I think the commercial sponsors recognise the quality of the trials and the evidence that they generate in Australia in contradiction to elsewhere in the world.”

What factors do surgeons and patients need to consider when deciding if scaffolds are an option, and how important is that shared decision making?

“Scaffolds are not currently an option other than in the context of the clinical trial. And so in order for a patient who’s interested, and we have a lot of experience with this because once we sort of announced that the trial was happening, it really captured people’s imagination because these are women who have lived for a very long period of time with their silicone prostheses and have come to experience all of the problems associated.”

“There is a genuine need and a want for an alternative that can create a certain level of desperation which needs to be kind of kept in check. As part of the trial process, there really is a very involved dialogue between the investigator and the patient with the declaration of all conflicts associated.”

“In a sense, trial patients get very well looked after, and there’s a certain measure of safety in being involved in a clinical trial, certainly in this part of the world as I mentioned earlier. So, I think that dialogue is pretty strong.”

“The, the unfortunate thing, as I mentioned, is that because it captures people’s imagination, this idea of a bioresorbable implant and replacing a tissue defect with something that is inherently the patient’s own tissue with a very low surgical morbidity can lend itself to being misused in some respects.”

“And that’s why we have to put the brakes on, and make sure we progress through all the levels of evidence that are required, so we understand fully how the device works, and what its limitations are because there will be limitations and there’ll be circumstances where it’s not actually the right device for a given patient.”

“However, as I mentioned, it’s entirely what it is; it is likely, and the evidence is certainly suggesting that this is a much safer option than what’s currently available on the market.”

When you think about scaffold technology continuing to evolve over the next 5-10 years, what makes you most excited about the future in this area?

“It’s a really interesting question because what’s achievable in five to 10 years is very much in the realm of what I was thinking about 5 or 10 years ago. Do you know what I mean? So, for me, thinking about the next 5 to 10 years is terrifically boring because it’s stuff that I feel like we’ve already negotiated and as a scientist, we’re always thinking several steps ahead.”

“But I would very much like to see silicon prostheses intended for permanent implantation removed from the market within 10 years, certainly. And that’s not to say that we should replace all of them with scaffold devices necessarily.”

“More than that, what I’d really like is for society at large to stop obsessing about the volume of the female breast and accept people just as they are. And that’s relevant in the breast augmentation space.”

“It’s actually a very complex thing because that’s not to say that any woman should be denied breast augmentation because there are many, many different indications for it.

“But I’d love to see a society that just doesn’t really see a need for cosmetic breast augmentation anymore. And I’d probably like that more than anything to do with the scaffold.”