Peek behind the paper: building macro tissues from the nanoscale

In this feature, Jason Wong (University of Manchester; Manchester, UK) peeks behind his review paper evaluating the current and future applications and challenges concerning nanomedicine in reconstructive surgery.

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Nov 20, 2019
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Please could you introduce yourself and your institution?

I am a senior clinical lecturer and academic consultant in plastic and reconstructive surgery in the Division of Cell Matrix Biology and Regenerative Medicine at the University of Manchester and Manchester University Foundation Trust (both Manchester, UK). I am the deputy director for the Tissue Engineering and Regenerative Medicine Masters programme at the University, and a King James IV Professor for the Royal College of Surgeons Edinburgh.

What prompted you to conduct this review?

I was compelled to contribute to this exciting compendium on the future directions of transplantation and regenerative surgery following an invitation from a leading academic plastic surgeon. We are at a very exciting time within my research group – and wider in our division at the University of Manchester. Several principal investigators are working on technologies at the cellular and subcellular levels that could impact on the future of plastic and reconstructive surgeries. This review paper provided a great opportunity to tie together all our research interests and pursuits, as there will be translational opportunities in the various topic areas in the future.         

What are some of the challenges associated with current tissue engineering technologies; how have these been limited by scalability, integration and vascularity?

Communication and education around tissue engineering between scientists and into the clinical arena is limited. Lots of incredible science is being performed in silos without true integration between material scientists, engineers, biologists, regulators and clinicians. As a result, engineered designs may not always be fit for requirement, due to surgery moving forward, new cures being identified or simply because end users are not convinced of a products’ superiority over conventional options. This is a challenge often overlooked by scientists; the engineering of new tissues needs to continue evolving, mimicking biology and potentially surpassing evolutional constraints. To make this feasible, we must be able to replace the elements that are essential for all living tissues – i.e. their immune-privileged cells and matrices that are supplied with means of nutritional and waste exchange.

        …the engineering of new tissues needs to continue evolving, mimicking biology and potentially surpassing evolutional constraints.”

Over the last decade, many technologies to enable this have been developed on a small scale. As a result, they were able to overcome challenges associated with nutritional diffusion. However, as we move towards clinically relevant tissues of human scale, engineering the blood supply and connecting that blood supply to the host will be the major obstacle to ensuring translation and clinical adoption of these technologies.

How has nanomedicine helped foster the development of biomimetic materials and what benefits may these offer, for example, for regenerative devices or drug delivery?

There are many properties of materials at the nanoscale that influence the behavior of cells in interesting ways. Some of these were expected, such as fibrous architecture providing a more collagen-like integration. Others were not predicted, for example the potent antimicrobial properties that nanoparticles have been demonstrated to exert. With this vast array of biological effects, nanoscale engineering allows us to better ‘tune’ existing technologies and improve the efficacy of these devices and therapies.

How may recent advances in nanomedicine progress tissue, nerve and vascular engineering, and ultimately advance reconstructive surgery?

The art of transferring tissues from one part of the body to another, for the purpose of replacing damaged or missing parts, has been mastered by many a reconstructive surgeon. However, an individual’s biology and physiology still make predicting their healing difficult and poorer than it could be. Scarring, loss of sensation or tissue necrosis due to inadequate blood supply remain the most common issues faced by reconstructive surgeons.

         …nanoscale engineering allows us to better ‘tune’ existing technologies and improve the efficacy of these devices and therapies.”

Manipulating these at the nanoscale provides a realistic option for us to improve patients’ outcomes. Simple advances – such as producing tissues with prefabricated channels or pores that allow them to vascularize quickly, biomimetic coatings on implants, or grooves in nerve conduits to make regeneration occur more quickly – demonstrate how nanomedicine will impact on the next generation of devices for reconstructive surgery.

How may nanomedicine advancements allow for the repurposing of older technologies and a ‘therapeutic revolution’?

Many older technologies work to some degree – as proven by vast preclinical studies. However, engineering limitations during these products’ development mean that they often fail to break through to clinics. Nanomedicine may potentially allow for the repurposing of these technologies by tuning their functionality at the nanoscale. For example, by binding drugs or therapies to nanoparticles, the pharmacodynamics of the former may be dramatically changed, as will the contact time and/or biodegradability of the compound. Alterations in these can make formerly toxic substances therapeutic. This also allows for a far less wasteful and costly process as you are building a technology from existing foundations rather than starting from scratch.

How do you see the future of nanomedicine and biomimicry in reconstructive surgery and tissue engineering evolving?

There is already a growing presence of nanotechnology in reconstructive surgery, but it is probably regarded as a bit of a fad for now as no one really understands what it means. Only over the last decade has the concept of super-microsurgery really begun permeating mainstream practice. Surgeons tend to believe what they can see; the concept of nanomedicine in surgical terms will inevitably require some getting used to.

        Demonstrating the true biological benefits of nanomedicine will be crucial to its mainstream adoption.”

Demonstrating the true biological benefits of nanomedicine will be crucial to its mainstream adoption. Tissues that look, feel and move just like normal tissues at the macro level, but have been engineered at the nanoscale level, will probably take some time to impact on patient care. Focusing, at least initially, on wound healing applications, we will see the earliest adoption of nanomedicine in next generation dressings and implant coatings. Full tissue replacements are probably not as far away as we think, but the initial impact of reconstructive nanomedicine applications will be in disease modeling and advanced assays. It’s going to take a bit of convincing of clinicians that there are gains to be had with nanomedicine, but hopefully our review will help demystify the broad range of emerging technologies and convince other surgeons of its value in the future of reconstructive surgery.

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