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

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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.