Improving biological integration of osseous and dermal tissues in macaque cranial implants

改善猕猴颅骨植入物中骨组织和真皮组织的生物整合

• 批准号: NC/P000940/1
• 负责人: Alexander Thiele
• 金额: $ 27.34万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NC%2FP000940%2F1
• 关键词: Improving; biological; integration; osseous; dermal

Non-human primates (NHPs) are an indispensable model in neuroscience research. Their brains are sufficiently similar to our own that they can provide important insights into how the human brain works, which can help to develop a variety of medical treatments. Unlike research with humans, it is possible to use invasive techniques in NHPs, to understand how neurons are organized, how they communicate, and which brain chemicals mediate their communication. Many of the studies employing NHPs require surgical implantation of a headpost and a recording chamber under general anaesthesia. These 'cranial implants' are required to keep the animals' heads motionless during experiments in order to obtain functional magnetic resonance imaging (fMRI) data or electrophysiological recordings. The implants are anchored to the skull by means of surgical screws, and the skin is closed around them. The implants generally integrate well with the underlying bone, due to the use of modern biocompatible materials. However, they often suffer from imperfect skin closure around the part of the implant that is exposed. Imperfect skin closure often results in infection of the skin and other soft tissue, which can lead to skin retraction and extension of the wound margin. Animals may need their wounds regularly cleaned once infected, and where infections prove difficult to clear, they may infect the bone and lead to implant loss. Consequently, there is an urgent need to refine the designs of cranial implants in order to reduce the health risks to the animals, and significantly improve animal welfare. These developments should be centred on improving the integration of soft tissue and skin with the implant, in order to prevent and reduce implant infection and its associated complications. We will use recent developments in human clinical studies (and animal preclinical studies) that have improved soft tissue integration in prostheses that have similar requirements to cranial implants, i.e. they need to be anchored to the bone, but protrude through the skin. By adding specific porous materials and/or changing the shape of those parts of the implant that are in direct contact with the skin, skin cells more effectively anchor to the implant, which improves wound healing. The success of these approaches has been outstanding, but they have yet to be applied to the use of primate cranial implants. By adding porous materials to existing implant designs for NHPs, our aim is to substantially improve the integration of the skin with the implant, thereby reducing inflammation and infection rates, and improving animal welfare. Importantly, our approach employs novel techniques for implant production (3-D printing), which can now produce implants using the most biocompatible materials (e.g. zirconium ceramics, hydroxyapatite), which are tailored to each individual animal. This printing technology is also now widely available, ensuring that neuroscience laboratories worldwide will be able to produce similar implants for their own animals. To ensure this, we will develop an instruction and software package (a 'workflow'), that is open source, and easy and cheap to implement by different laboratories, so they can generate their own 3-D printing model, starting with a 3-D MRI model of the animal skull and a basic outline sketch of an implant of the desired shape. We predict that our project will reduce infection rates, reduce discomfort associated with infected implants, reduce instances of implant failure, and significantly improve animal welfare. It will also potentially lead to some reductions in the numbers of animals used, by increasing the quality and quantity of scientific data obtained, as fewer animals will be necessary to obtain a scientific objective.

非人灵长类动物是神经科学研究中不可或缺的模型。它们的大脑与我们的大脑非常相似，可以为人类大脑如何工作提供重要的见解，这有助于开发各种医学治疗方法。与人类研究不同，在NHP中使用侵入性技术是可能的，可以了解神经元是如何组织的，它们如何交流，以及哪些大脑化学物质介导它们的交流。许多使用NHP的研究需要在全身麻醉下手术植入头柱和记录室。这些“颅骨植入物”需要在实验期间保持动物的头部不动，以便获得功能性磁共振成像（fMRI）数据或电生理记录。植入物通过外科螺钉固定在颅骨上，并将其周围的皮肤封闭。由于使用了现代生物相容性材料，植入物通常与底层骨结合良好。然而，他们经常遭受植入物暴露部分周围的皮肤闭合不完美。不完美的皮肤闭合通常导致皮肤和其他软组织的感染，这可导致皮肤回缩和伤口边缘的延伸。一旦感染，动物可能需要定期清洗伤口，如果感染难以清除，它们可能会感染骨骼并导致植入物丢失。因此，迫切需要改进颅骨植入物的设计，以减少对动物的健康风险，并显着提高动物福利。这些发展应集中在改善软组织和皮肤与植入物的整合，以预防和减少植入物感染及其相关并发症。我们将使用人类临床研究（和动物临床前研究）中的最新进展，这些进展改善了假体中的软组织整合，这些假体与颅骨植入物具有相似的要求，即它们需要锚定到骨骼上，但突出皮肤。通过添加特定的多孔材料和/或改变与皮肤直接接触的植入物的那些部分的形状，皮肤细胞更有效地锚到植入物，这改善了伤口愈合。这些方法的成功是突出的，但它们尚未应用于灵长类动物颅骨植入物的使用。通过将多孔材料添加到现有的NHP植入物设计中，我们的目标是大幅改善皮肤与植入物的整合，从而降低炎症和感染率，并改善动物福利。重要的是，我们的方法采用了新的植入物生产技术（3D打印），现在可以使用最具生物相容性的材料（例如锆陶瓷，羟基磷灰石）生产植入物，这些材料是为每只动物量身定制的。这种打印技术现在也被广泛使用，确保世界各地的神经科学实验室能够为自己的动物生产类似的植入物。为了确保这一点，我们将开发一个指令和软件包（“工作流程”），这是开源的，并且容易和便宜地由不同的实验室实施，因此他们可以生成自己的3D打印模型，从动物头骨的3D MRI模型和所需形状的植入物的基本轮廓草图开始。我们预测，我们的项目将降低感染率，减少与感染植入物相关的不适，减少植入物失败的情况，并显着改善动物福利。它还可能通过提高所获得的科学数据的质量和数量，减少使用的动物数量，因为实现科学目标所需的动物数量将减少。