Macaques are used in neuroscience for fundamental research understanding brain function, including cognition, vision and motor control research fields. This research can also aid in the development of medical treatments. Many neuroscientific studies involving macaques require surgical implantation of a “cranial implant”, consisting of a headpost and recording chamber, under general anaesthesia. Cranial implants are anchored to the skull by surgical screws and are required to stabilise the animal’s head during experiments, to minimise recording artefacts. Modern implants integrate well with the underlying bone due to the use of biocompatible materials. However, the implants often suffer from poor dermal integration and imperfect skin closure surrounding the exposed part of the implant. Imperfect skin closure can lead to infection of the skin and other soft tissues, which can spread to the bone leading to implant loss. This has implications for the welfare of the animals and can result in an early termination of the study if the implant is lost.
Why we funded it
This Strategic Grant aims to refine the use of macaque cranial implants by using recent advances in human percutaneous prosthesis to reduce infection and implant failure rates.
A review published by the Animal Procedures Committee assessing the lifetime experience of non-human primates used in neuroscience research identified skin infections relating to the cranial implant as one of the most reported adverse effects. Low-level skin infections around the cranial implant were reported in 67% of 61 macaques reported, of which 40% had adverse effects of complications. Data for the review was reported from users in UK and EU institutions. Improving the dermal integration of the implants will improve the welfare of approximately 12 animals per year at Newcastle University. If the refined cranial implant design was adopted by the majority of UK laboratories performing similar experiments it could benefit approximately 30 to 40 animals annually in the UK.
Advances in human percutaneous prosthesis have identified two approaches that improve dermal integration. The first approach is to add a porous flange that is in direct contact with the dermis, whereas the second approach alters the porosity of the implant surface itself. Both approaches allow incorporation of native tissue into the implant as the porosity allows cells and blood vessels to infiltrate parts of the implant. No direct comparison of the two methods has been performed, either in animal studies or human prosthesis. This project will determine the benefits of each approach in macaque cranial implant integration. Benefits will be quantified based on clinical observations (wound-picking, signs of infection, tissue samples), radiological and MR imaging of the skull and skin, microbiological assessment of wound margin samples, and post-mortem histological assessment. To ensure improvements can be adopted by external researchers, an instruction and software package will be developed to generate 3D computer implant models from which medical grade implants can be manufactured, either by computer aided design or 3D printing.
Ortiz-Rios M, Haag M, Balezeau F, Frey S, Thiele A, Murphy K, Schmid MC (2018). Improved methods for MRI-compatible implants in nonhuman primates. J Neurosci Methods [epub ahead of print] doi: 10.1016/j.jneumeth.2018.09.013
Principal investigatorProfessor Alex Thiele
Co-InvestigatorDr Andrew Jackson
Dr Demetris Soteropoulos
Dr Michael Schmid
Dr Christopher Petkov
Professor Stuart Baker