气凝胶,世界上最轻的固体,可帮助骨骼更快地愈合
Aerogel, the world’s lightest solid, can help bones heal faster
2058字
2020-01-06 14:47
59阅读
火星译客

Cell Biology

细胞生物学

National Centre for Biological Sciences

国家生物科学中心

November 12, 2019 3 peer comments

2019年11月12日,3个同行评论

Regrowing bones is no easy task, but the you/tube.com/watch?v=AeJ9q45PfD0">world’s lightest solid might make it easier to achieve. Researchers have figured out a way to use hybrid aerogels, strong but ultralight materials, to prompt new bone tissue to grow and replace lost or damaged tissue.

骨骼再生并非易事,但You/tube.com/watch?v=AeJ9q45PfD0“>世界上最轻的固体可能会让它更容易实现。研究人员已经找到了一种使用混合气凝胶的方法,这种坚固但超轻的材料可以促进新的骨组织生长,并取代丢失或受损的组织。

Although bone cancer is a relatively rare disease (it accounts for less than 1% of all cancers), people who suffer from it often end up losing a lot of bone tissue and in extreme cases, undergo amputation. The cancerous tissue has to be cut out, taking with it a large chunk of nearby healthy tissue to make sure that the cancer does not spread. This effectively removes the cancer, but also leaves the patient with a lot less bone than they started out with.

虽然骨癌是一种相对罕见的疾病(它在所有癌症中所占比例不到1%),但患有骨癌的人最终往往会失去大量骨组织,在极端情况下,还会接受截肢手术。癌组织必须进行切除,同时带走附近的一大块健康组织,以确保癌症不会扩散。这有效地移除了癌症,但也让患者的骨骼比开始时少了很多。

It turns out that bone tissue just needs a little bit of encouragement to regenerate. 

其实,骨组织只需要一点点激励就可以再生。

A recent study has used hybrid aerogels to restore the lost tissue by prompting bone regeneration. Aerogels are basically a combination of solid and gas. Think Jell-O, but one where the water has been slowly dried out and replaced completely by air. This slow and careful removing of liquid is what allows the gel to retain its shape instead of shriveling into a hard lump. The pairing of solid and gas makes aerogels extremely light and very porous. These two qualities make them exceptionally suitable to use as scaffolds, which can be used as physical roadmaps for the developing bone to follow as it grows. 

最近的一项研究使用混合气凝胶通过促进骨骼再生来修复丢失的组织。气凝胶基本上是固体和气体的混合物。凝胶类似果冻,但在气凝胶中,水份已经慢慢蒸干,完全被空气所取代。这种缓慢而小心的液体去除使凝胶保持其形状,而不是萎缩成坚硬的块状。固体和气体的配对使得气凝胶非常轻,非常多孔。这两个特性使它们特别适合作为支架使用,这可以作为发育中的骨骼在生长过程中遵循的物理路线图。

Currently, the most common methods of bone regeneration either graft new bone on to the repair site or slowly pull two bits of bone further and further apart to allow new bone to grow in the gap. If you think that these methods sound painful, complicated, and expensive, you are right. 

目前,最常见的骨再生方法要么是将新骨移植到修复部位,要么是慢慢地将两块骨拉得越来越远,以便让新骨在缝隙中生长。如果你认为这些方法听起来痛苦、复杂和昂贵,那么你是对的。

A section of bone with osteosarcoma, a type of bone cancer.

 A section of bone with osteosarcoma, a type of bone cancer. This is one of the cases where lost tissue could be restored by prompting bone regeneration.

具有骨肉瘤的一部分骨骼,属于骨癌的一种。这是通过促进骨再生可以修复丢失的组织的案例之一。

由Nephron提供。

It turns out that bone tissue just needs a little bit of encouragement to regenerate. Most of the time, simple mechanical pressure will do the trick. The fiddly bit is getting the new bone tissue to grow in the right direction and for the right amount of time. Stop it too early and the bone will be too weak to actually serve a purpose. Let it grow too much and it will end up as painful projections

事实证明,骨组织只需要一点点的激励就能再生。大多数情况下,简单的机械压力就能起到作用。最麻烦的是让新的骨组织朝着正确的方向生长,并持续合适的时间。过早地停止,骨头就会太弱,不能真正发挥作用。让它增长太多,它最终将形成疼痛的骨组织突出。

This balanced growth can be achieved by using a scaffold, which is where hybrid aerogels come in. A scaffold is a structure that is placed at the site of bone repair, where it guides the growing tissue along its destined path. A good scaffold is strong but not too stiff, lasts just long enough for fresh tissue to develop, and has a lot of pores for the growing bone to snake through. This last bit is what makes a scaffold very similar to real bone. Hybrid aerogels happen to be a magic material that hits all these notes.

这种平衡的增长可以通过使用支架来实现,这就是混合气凝胶的用武之地。支架是放置在骨修复部位的一种结构,它用以引导生长的组织沿着其预定的路径生长。一个好的支架是坚固的,但不会太硬,持续的时间刚好可以让新组织生长,并且有很多孔隙可以让成长中的骨骼蜿蜒穿过。这最后一点使支架非常类似于真正的骨头。混合气凝胶碰巧是一种神奇的材料,可以匹配所有这些要求。

There are a lot of different kinds of scaffolds to choose from, ranging from ceramic and metals to cellulose hydrogels. So what makes hybrid aerogels any better than other scaffolds? For one, they are half made of proteins (that’s the “hybrid” bit), which are eventually broken down by the body. The other half, silica, slowly melts away as orthosilicic acid, which is known to hasten wound healing. Their pore size can be controlled during the manufacturing process, making it easy to adapt them to different uses. They are also being tested as drug delivery systems, meaning that the material could be spiked with medicines or growth factors before using it as a scaffold.

有很多不同种类的支架可供选择,从陶瓷、金属到纤维素水凝胶,不一而足。那么,是什么让混合气凝胶比其他支架更好呢?首先,它们有一半是由蛋白质(“杂交”部分)组成的,这些蛋白质最终会被身体分解。另一半是二氧化硅,以原硅酸的形式慢慢融解,众所周知,原硅酸可以加速伤口愈合。它们的孔径可以在制造过程中控制,使其很容易适应不同的用途。它们还在作为药物输送系统进行测试,这意味着在将材料用作支架之前,可以在材料中添加药物或生长因子。

Earlier this year, three research labs based out of Iran, Germany, and Austria got together and decided to fuse a very strong protein with a very light and porous aerogel. The very strong protein is silk fibroin, the stuff found in silkworm cocoons and used to make fancy fabrics. It makes the aerogel strong and just stiff enough to use for bone growth. With the raw materials ready, the scientists started with Phase I: make the hybrid aerogel. Throw a source of silica, silk fibroin, some acid and a touch of detergent into a pot. Bake for an hour and voilà! You have yourself a silica-silk fibroin hybrid aerogel. 

今年早些时候,来自伊朗、德国和奥地利的三个研究实验室聚集在一起,决定将一种非常强大的蛋白质与一种非常轻和多孔的气凝胶融合在一起。这个非常强的蛋白质是丝素蛋白,这是一种在蚕茧中发现的物质,用于制作奇特的织物。它使气凝胶变得坚固,硬度刚好可以用来生长骨骼。准备好原材料后,科学家们开始了第一阶段:制造混合气凝胶。往反应器中倒入一定量的二氧化硅、丝素、一些酸和一点洗涤剂。烘烤一个小时,瞧!你可以得到一种硅胶-丝素混合气凝胶。

Aerogelflower_filtered.jpg?auto=compress%2Cformat

 Hybrid aerogels are strong but ultralight materials. Here, the flower is protected from the fire by the insulating properties of the aerogel.

混合气凝胶是一种坚固但超轻的材料。如上图,气凝胶的隔热特性可以保护花朵免受火焰的侵袭。

Of course, the researchers faced their fair share of hurdles along the way. The first material they made was too hydrophobic (it repelled water, not good for a body that is 70% water), the second one was too stiff and dry, and the third one would have just sat around in the body forever without degrading. Finally, the fourth one hit the mark and they made the perfect hybrid aerogel – hydrophilic (water-loving), not too stiff, and adequately biodegradable.

当然,研究人员在这一过程中也面临着相当一部分的难关。他们制造的第一种材料太疏水(它排斥水,对70%由水组成的人体不亲和),第二种材料太硬太干,第三种材料会永远留在身体里而不会降解。最后,第四个达到了目标,他们制造出了完美的气凝胶-亲水性(亲水)混合材料,不会太僵硬,而且具有足够的可生物降解性。

Having made the material, they now moved to Phase II: check if the hybrid aerogels are in any way harmful to human cells. The scaffold was put through a series of tests and deemed to be perfectly safe to use with human cells. In fact, the cells seemed to really like the material. When the hybrid aerogel was placed in a dish containing bone cells, they readily grew on its surface, depositing the proteins and minerals required for bone growth along the way. 

完成材料的制作后,他们现在进入第二阶段:检查混合气凝胶是否以任何方式对人体细胞有害。这种支架经过了一系列测试,被认为与人类细胞一起使用是完全安全的。事实上,这些细胞似乎真的很喜欢这种材料。当混合气凝胶被放入装有骨细胞的培养皿中时,它们很容易在其表面生长,沿途沉积骨生长所需的蛋白质和矿物质。

The aerogel was not just allowing new bone to grow, but also making it grow faster than normal. 

这种气凝胶不仅可以让新骨生长,还能让它比正常情况下生长得更快。

On to Phase III: implant the hybrid aerogel in mice and check if it stimulates bone regeneration. The researchers made small bone injuries in two groups of mice and implanted the hybrid aerogel in one of them. After 25 days, they saw that the mice with the implants showed faster and better healing than the mice without implants. The aerogel was not just allowing new bone to grow, but also making it grow faster than normal. 

继续到第三阶段:将混合气凝胶植入小鼠体内,检查它是否刺激骨再生。研究人员在两组老鼠身上造成了轻微的骨骼损伤,并在其中一组老鼠身上植入了混合气凝胶。25天后,他们发现有植入物的老鼠比没有植入物的老鼠愈合得更快、更好。这种气凝胶不仅可以让新的骨骼生长,而且还能让它比正常情况下生长得更快。

This ability of the hybrid aerogel to speed up bone regeneration places it on the forefront of new therapeutic technologies. Imagine having bone fractures healing in a span of days, as opposed to weeks. Or being able to tell a bone cancer patient that, “Yes, you have to cut out a section of their leg but it can be easily grown back, no worries.” Hybrid aerogels are possibly the biomaterial that could make such conversations a reality. 

这种混合气凝胶加速骨骼再生的能力使其走在了新治疗技术的前沿。想象一下,骨折在几天内愈合,而不是几周。或者能够告诉骨癌患者,“是的,你必须切除他们的腿的一部分,但它可以很容易地长出来,不用担心。”混合气凝胶可能是使这种对话成为现实的生物材料。

Peer Commentary

同行评论

We ask other scientists from our Consortium to respond to articles with commentary from their expert perspective.

我们要求我们联盟的其他科学家从他们的专家角度对文章进行评论。

emily%20deibert.jpg?auto=compress%2Cformat&crop=faces&fit=crop&fm=jpg&h=60&q=75&w=60

Astronomy and Astrophysics

天文学和天体物理学

University of Toronto

多伦多大学

This is so interesting. The technology sounds very promising! It’s also really interesting to hear about the varied applications of the hybrid aerogels, including for patients with bone cancer. What I’m wondering  about is the cost of using hybrid aerogels to speed up bone regeneration compared to the cost of bone grafts or other more traditional methods. It sounds like the benefits of the hybrid aerogel method are (1) that it’s much faster, and (2) that it’s less painful and complicated, but is it comparable in price as well? Great article!

这太有趣了。这项技术听起来很有前途!听到混合气凝胶的各种应用,包括对骨癌患者的应用,也是非常有趣的。我想知道的是,与骨移植或其他更传统的方法相比,使用混合气凝胶来加速骨再生的成本是多少。听起来,混合气凝胶方法的好处是(1)速度更快,(2)痛苦和复杂更少,但它的价格也具有可比性吗?很棒的文章!

2170_2.png?auto=compress%2Cformat&crop=faces&fit=crop&fm=jpg&h=60&q=75&w=60

Hi Emily, thanks for the commentary! You’re right to consider the cost - currently, even at the small scale of lab preparations, silica aerogels  are more pricey than existing treatments. Making aerogels for other  purposes, like insulation for satellites, is actually something that has been worked out and optimised. Making them for biological purposes is  what brings in the cost. I suppose if the technique gains enough  traction there will be groups working on scaling up production in a cost-effective manner. This is already being done for cellulose-based  hybrid aerogels because cellulose is a cheaper and easier biopolymer to work with than silk fibroin. For silk fibroin, I think they still need  more experiments to properly assess whether the technique is suitable for the market or not. Hopefully we’ll see some follow-up studies soon. 

嗨,Emily,谢谢你的评论!你考虑成本是正确的-目前,即使是在实验室准备的小规模试验,二氧化硅气凝胶也比现有的治疗方法更昂贵。制造气凝胶用于其他目的,比如卫星的绝缘,实际上是已经设计出来并优化的东西。制造它们用于生物目的是带来成本的原因。我想,如果这项技术获得足够的吸引力,将会有一些小组致力于以具有成本效益的方式扩大生产。这已经被用于纤维素为基础的混合气凝胶,因为纤维素是一种比丝素更便宜、更容易使用的生物聚合物。对于丝素,我认为他们还需要更多的实验来正确评估这项技术是否适合市场。我们有望很快能看到一些后续的研究。

2142_2.png?auto=compress%2Cformat&crop=faces&fit=crop&fm=jpg&h=60&q=75&w=60

I am always excited to learn about ways that scientists from all around the world collaborate together to make a difference. I am super impressed that the use of this aerogel still allows for the bone to grow back with comparable density to the non-implanted animals (Fig 7, I think it was?). I do wonder, why/how did they decide to use the protein from the silkworm, specifically? is it typical in this field? 

我总是很兴奋能了解到来自世界各地的科学家如何合作做出改变。令我印象深刻的是,使用这种气凝胶仍然允许骨骼以与未进行植入的动物骨骼相当的密度重新生长(图7,我认为是?)。我确实想知道,他们为什么/如何决定特别使用家蚕中的蛋白质?这是这个领域的典型吗?

2170_2.png?auto=compress%2Cformat&crop=faces&fit=crop&fm=jpg&h=60&q=75&w=60

Hi Grace, thanks for the commentary! From what I read it looks like they were testing out silk fibroin for other experiments with tensile strength and from there, decided to test it with aerogels. Unfortunately I didn’t get a response from the authors when I asked them this, so I can only guess.

嗨,Grace,谢谢你的评论!据我所知,他们似乎正在测试丝素蛋白用于其他抗张强度的实验,并决定从那时开始用气凝胶进行测试。不幸的是,当我问作者这个问题时,他们没有回答,所以这只是我的猜测。

The field more commonly uses collagen or starch as the biopolymer component, so silk fibroin is definitely an unusual candidate.

该领域通常使用胶原或淀粉作为生物聚合物成分,因此丝素蛋白绝对是一个不同寻常的候选者。

1739_2.png?auto=compress%2Cformat&crop=faces&fit=crop&fm=jpg&h=60&q=75&w=60

Great article Sruthi! I am a huge fan of aerogels-- mainly because of their super cool materials properties. Did you know that silica aerogels are blue for the same reason that the sky is?! Rayleigh scattering! (I would advise someone not to hold it in their bare hand as in the photo, however. These materials --silica only ones, are typically extremely hydrophilic, so they will suck up moisture from your hands and make them cloudy.) It’s cool to see them used for a different applications other than collecting space dust!

很棒的文章,Sruthi!我是气凝胶的铁杆粉丝--主要是因为它们具有超酷的材料特性。你知道硅气凝胶是蓝色的原因和天空是一样的吗?!瑞利散射!(然而,我建议某人不要像照片中那样赤手空拳地拿着它。这些材料--仅含二氧化硅的材料--通常都非常亲水,所以它们会吸走你手上的水分,使它们变得浑浊。)看到他们被用于不同的用途,而不是收集太空灰尘,这真是太酷了!

Bone regeneration is also a big problem- not just for bone cancer. When you break a bone as a kid, no problem- you’re bones are growing anyways and healing them is easy, but as an ad/ult it’s more difficult. Yet, even though bone stops growing when you’re an ad/ult, it still is in a constant state of flux- constantly being created and replaced. Doctors often use metal (titanium) plates to repair broken bones, but there are disadvantages to this. The metal absorbs more force than bone, so the bone around it ends up responding and weakening around the metal, which can lead to more issues (especially with hip replacements). Ideally, we would want a material that can trick our body into thinking it is bone and have the cells create and replace new bone. Whether this aerogel composite did that or not is still undetermined, but I imagine the material properties are a lot more similar to bone than metals are!

骨再生本身也是一个大问题--不仅仅是因为骨癌。当你还是个孩子的时候折断了一根骨头,没有问题--你的骨头无论如何都在生长,愈合它们是很容易的,但作为一个成年人,这就更难了。然而,即使骨骼在你成为成人时停止生长,它仍然处于不断变化的状态-不断地被创造和替换。医生经常使用金属(钛)板来修复骨折,但这样做也有缺点。金属比骨骼吸收更多的力,所以它周围的骨骼最终会做出反应,在金属周围变弱,这可能会导致更多的问题(特别是髋关节置换)。理想情况下,我们希望有一种可以欺骗我们的身体,认为它本身就是骨骼的材料,并让细胞产生和替换新的骨骼。这种气凝胶复合材料是否做到了这一点还没有确定,但我想这种材料的特性比金属更类似于骨骼!

Bone is an amazing material. It’s hierarchically structured, which means there is order on every length scale: nano-, micro-, macro-! It’s ~30% organic and 70% mineral, and the organic part is extremely important for its structure and material properties. I think the use of both a silica aerogel and silk protein is a creative way to achieve similar material properties to bone.

骨骼是一种令人惊叹的材料。它是有层次结构的,这意味着在每个长度尺度上都有秩序:纳米、微观、宏观!其有机含量约为30%,矿物质含量约为70%,其中有机部分对其结构和材料性能起着极其重要的作用。我认为,同时使用硅气凝胶和丝蛋白是一种创造性的方式,可以获得与骨骼相似的材料特性。

Aside:  I would argue that the paper didn’t examine the healing properties enough on a cellular level… they looked at whether it was harmful via blood analyses and for “regeneration” - but this was using bone density measurements, which could easily mistake silica for bone. I would want to see the bone cells grow into the material!

PS:我会在意这篇论文没有在细胞水平的上对愈合特性进行足够的检查...他们通过血液分析和“再生”来研究它是否有害-但这是使用骨密度测量,这种测量方法很容易将二氧化硅误认为骨骼。我希望看到骨细胞长入材料中!

2170_2.png?auto=compress%2Cformat&crop=faces&fit=crop&fm=jpg&h=60&q=75&w=60

Thanks so much for the commentary, Chelsea! I agree, there was definitely a lot left wanting in terms of the cellular experiments. I think the closest thing they did was to conduct in vitro tests where they seeded bone cells on the scaffold and saw the cells growing all over the material. They don’t explicitly say whether the cells went in through the pores or not, but given that the porosity of the aerogel is one of their main selling points, I’m assuming they must have checked it. Hopefully we’ll see more cool stuff in the future.

非常感谢你的解说,Chelsea!我同意,就细胞实验而言,肯定还有很多需要改进的地方。我认为他们做的最接近的事情是进行体外试验,他们在支架上种植骨细胞,然后看到细胞在材料上生长。他们没有明确说明细胞是否通过孔隙进入,但考虑到气凝胶的孔隙率是他们的主要卖点之一,我猜他们一定是检查过了。希望我们在未来能看到更多很酷的东西。

0 条评论
评论不能为空