[Paper Review] Magnetic matrix actuation for programming tissues

 

 

 

* 인터뷰 내용이 흥미로워서 찾아본 논문 

• Mechanically programming anisotropy in engineered muscle with actuating extracellular matrices
• https://www.cell.com/device/fulltext/S2666-9986(23)00175-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2666998623001758%3Fshowall%3Dtrue
• https://www.sciencedirect.com/science/article/pii/S2666998623001497

 

 

 

* 추가로 찾아본 해당 연구실 연구들 

https://ramanlab.mit.edu/publications/

 

Leveraging microtopography to pattern multi-oriented muscle actuators (2024)

https://www.biorxiv.org/content/10.1101/2024.07.31.606059v1

 

Biofabrication of Living Actuators (2024)

https://www.annualreviews.org/content/journals/10.1146/annurev-bioeng-110122-013805

 

Will microfluidics enable functionally integrated biohybrid robots? (2022)

https://www.pnas.org/doi/10.1073/pnas.2200741119

 

Engineered neuromuscular actuators for medicine, meat, and machines (2021)

https://link.springer.com/article/10.1557/s43577-021-00122-3

 

Biofabrication (2021, Book) 

https://mitpress.mit.edu/9780262542968/biofabrication/

 

Biohybrid actuators for robotics: A review of devices actuated by living cells (2017)

https://www.science.org/doi/10.1126/scirobotics.aaq0495

 

 

 

https://www.sciencedirect.com/science/article/pii/S2666998623001758

 

 

 

Magnetic matrix actuation for programming tissues 

 Professor Ritu Raman is a mechanical engineer at the Massachusetts Institute of Technology, where her work focuses on the development of soft robots using biological materials. The following discussion focuses on her group’s recent work published in Device and presents a magnetically actuated extracellular matrix that can be used to program morphological and functional anisotropy in tissues such as skeletal muscles. Importantly, this work highlights the potential to control a wide range of hydrogel chemistries for modulating complex multicellular tissues using magnetic forces.

 

 

 

Introduction

When Ritu Raman says that she’s flexing her muscles, she doesn’t (necessarily) mean what you might think. As an assistant professor of mechanical engineering at the Massachusetts Institute of Technology (MIT), she’s taken a keen focus on making muscle tissue respond to external stimulus in a predictable way, just like you would an actuator in a traditional robotics group. Ritu uses biological materials and engineering tools to build living neuromuscular tissues that, in addition to being key to developing biohybrid robots, offer a unique platform for studying how muscle actuation plays into the biology of disease, healing, and aging. In this backstory, we have discussed her recent work published in this issue of Device, entitled ‘‘Mechanically programming anisotropy in engineered muscle with actuating extracellular matrices.’’

 In this report, she and her colleagues present a device that addresses the fundamental limitations precluding our ability to control mechanical forces within multicellular systems. Her group developed a magnetically actuated extracellular matrix that mechanically stimulates cells within tissues with high spatiotemporal (시공간) control and tunable forces. As an impactful proof-of-concept demonstration, she shows that actuating hydrogels can control the directionality of fiber formation within engineered skeletal muscle. By mechanically programming anisotropy in muscle, it was possible to dynamically control the direction and synchrony of tissue-wide contraction, which has important implications for applications ranging from regenerative medicine to biohybrid robotics.

 

 

 

How do you think that your approach is different?

 We work at the mesoscale by creating millimeter- to centimeter-scale tissues. This ends up being a useful tool because you can capture the interaction between multiple motor units. The idea is to capture force generation behaviors on the tissue level that are not captured by the state-of-the-art in organoids or organ-on-a-chip devices where you’re looking at a few muscle fibers, a single nerve, or a single neuromuscular junction.

// 기존 scale에서는 포착할 수 없었던 interaction · behavior 를 capture 가능

 

 What sets us apart in the medical domain and in robotics is the great need for mesoscale (중규모의) resolution in understanding of biology. When you’re starting to think about how an injury in one region of the tissue might impact intercellular communication in another, mesoscale gives us a big advantage.

 

 There are very few labs working on biohybrid robotics at present, and I think we have sorted ourselves into different tissues of interest. My group works on mammalian skeletal muscle-powered robotics, and I believe we help lead that field.

 

 

 

It’s amazing that your tissues are working on the millimeter to centimeter scale. Can you describe the challenges when you are trying to build such a big tissue, especially at the centimeter scale?

 One of the big challenges associated with making tissues at the centimeter-length scale is that you need a lot of cells and reproducible manufacturing tools. It’s hard once you have cells embedded in a 3D construct to monitor them in the same way that you would be able to do in a 2D platform, so knowing exactly what goes into each tissue is very important.

 

 It’s important to note that our tissues are not vascularized yet. Most of our muscle tissues are thus on the order of half a millimeter to a millimeter in width - making thicker muscles would require integrating functional blood vessels for active nutrient transport.

// 큰 규모로 키울 경우, 내부에 산소와 양분 공급이 어려움 -> 괴사 (따라서 관이 필요한 것) 

 

 One big challenge in our work that you might not expect is that most research tools and instrumentation aren’t ideal for recording pictures and videos of actuating millimeter-scale tissues with high resolution and high frame rates. One of the biggest challenges we face on a week-to-week basis is just how we can take a good picture or a good video to showcase our work in a convincing and engaging way from a publication standpoint.

 

 

 

How did you fabricate the magnetic actuator that you used in your work?

 First, we realized that we could not buy something off the shelf that met our needs, so we had to build an actuating extracellular matrix in house. We made magnetic microparticles by mixing iron microparticles with biocompatible silicone and then created a sandwich: one layer of fibrin, one layer of magnetic microparticles, and another layer of fibrin.

 We then fabricated a linear actuator that would sit under a cell culture plate and move a permanent magnet back and forth under the gel. Depending on how fast you move the magnet, the strength of the magnet, the distribution of microparticles, and the angle of actuation, you can get the gel to move in a variety of different patterns. This is what we call MagMA. // 마그마라고 명명한 이유! 

+ anisotropy - 비등방성 - 방향에 따라 물체의 물리적 성질이 다름

 

 We made the gel actuate like it would during exercise if there was a muscle tissue sitting on it. We then tested whether this movement would have any impact on muscle. I thought maybe dynamic mechanical stimulation would make the muscle fibers stronger, but this did not seem to be true. (연구자의 구체적인 생각이나 실험 당시의 상황, 가정들도 엿볼 수 있어서 신기하다.) Instead, the big difference was in alignment. Muscles grown on actuating MagMA were highly aligned and demonstrated coordinated twitch in response to light stimulation.

 

 

 

What is your vision for the next 10 or 15 years? Let’s say there is a hypothetical world in which your experiments and science go exactly as you’d expect. How would that work for you?

 My goal for the next 10 to 15 years is to deploy biological robotics outside of a Petri dish and in a real-world environment. This a very new field, and we’ve been focusing on fundamental proof-of-concept demonstrations, but the next step is proving robustness and translational potential. So, if I had unlimited resources, I would love to make a robot that can function not just in my lab but also in my office and beyond!

 

 

 

+ 추후 읽을 논문 

- https://www.sciencedirect.com/science/article/pii/S2666998623001497