Healing Tissues via Programmable DNA Nanotechnology

生长因子是细胞产生和释放的强大生物蛋白质。它们在指导我们的细胞如何从一个卵细胞生长到大约30万亿个细胞的过程中发挥着关键作用，这些细胞以协调的方式排列起来，创造出一个人。它们的影响在我们的生活中也会持续；如果组织受损，比如骨折或皮肤上的伤口，生长因子会协调我们的组织愈合。由于这种强大的影响，生长因子是非常有吸引力的物质，用作促进组织修复的治疗药物。虽然有几种药物在世界各地的临床上使用，但由于疗效不佳和生产成本较高，它们的有效性、安全性和影响都远未达到最佳。因此，为了真正实现它们作为治疗药物的潜力，我们需要新的策略来彻底改变我们在临床上使用生长因子的方式。在这项提案中，我们将结合材料科学、纳米技术和生物学的各个方面，开发一种将生长因子用作疗法的变革性方法。我们的方法依赖于设计新型的纳米技术支持的材料，这种材料可以积极地从体内获取生长因子，然后用作治愈组织的疗法。这一策略将消除生产昂贵蛋白质的需要，极大地降低治疗成本。此外，它还将使以前批准的疗法适应组织修复的新领域，加快新疗法的开发，同时将生产成本降至最低。我们将展示我们的新方法修复临界大小的骨缺损的能力--即太大而不能自然愈合的骨缺损。这些数据构成了证明翻译到临床的合理性的关键组成部分，使这项提议有助于将这项令人振奋的新技术带到床边。

Growth factors are powerful biological proteins that cells produce and release. They have a key role in instructing our cells how to grow from one cell as an egg into approximately 30 trillion cells that are arranged in a coordinated fashion to create a person. Their influence also continues throughout our lives; if tissues are damaged such as a broken bone or wound on our skin, growth factors coordinate how our tissue heal. Because of this powerful influence, growth factors are highly attractive substances to use as therapeutics to promote tissue repair. While several are used in clinics around the world, their efficacy, safety, and impact are all far from being optimal due to sub-optimal efficacy and a high cost of production. Therefore, in order to truly realise their potential as therapeutics, we need new strategies that revolutionise how we use growth factors clinically. In this proposal, we will combine aspects of materials science, nanotechnology, and biology to develop a transformational approach to using growth factors as therapeutics. Our approach relies on designing novel nanotechnology-enabled materials that actively harvest growth factors from within the body to then use as therapeutics to heal tissues. This strategy will eliminate the need to produce expensive proteins, dramatically reducing the cost of treatment. Furthermore, it will enable the adaptation of previously approved therapeutics to new areas in tissue repair, speeding up the development of new treatments while also minimising production expenses. We will demonstrate the ability of our new approach to heal critical size bone defects - that is, bone defects that are too large to naturally heal on their own. This data forms a key component of justifying the translation to the clinic, making this proposal instrumental in bringing this exhilarating new technology to the bedside.