Biology subjects

Barone, D. G.

Publications and source records attributed to Barone, D. G..

4 recordsLinked to original sources

bioRxiv2023

Ultraconformable cuff implants for long-term bidirectional interfacing of peripheral nerves at sub-nerve resolutions

Implantable devices interfacing with peripheral nerves exhibit limited longevity and resolution. Poor nerve-electrode interface quality, invasive surgical placement and development of foreign body reaction combine to limit research and clinical application of these devices. Here, we develop cuff implants with an ultraconformable design that achieve high-quality and stable interfacing with nerves in chronic implantation scenarios. When implanted in sensorimotor nerves of the arm in awake rats for 21 days, the devices recorded nerve action potentials with fascicle-specific resolution and extracted from these the conduction velocity and direction of propagation. The ultraconformable cuffs exhibited high biocompatibility, producing lower levels of fibrotic scarring than clinically equivalent PDMS silicone cuffs. In addition to recording nerve activity, the devices were able to modulate nerve activity at sub-nerve resolution to produce a wide range of paw movements. The developed implantable devices represent a platform enabling new forms of fine nerve signal sensing and modulation, with applications in physiology research and closed-loop therapeutics.

neuroscience↗

bioRxiv2022

Regenerative capacity of neural tissue scales with changes in tissue mechanics post injury

Spinal cord injuries have devastating consequences for humans, as mammalian neurons of the central nervous system (CNS) cannot regenerate. In the peripheral nervous system (PNS), however, neurons may regenerate to restore lost function following injury. While mammalian CNS tissue softens after injury, how PNS tissue mechanics changes in response to mechanical trauma is currently poorly understood. Here we characterised mechanical rat nerve tissue properties before and after in vivo crush and transection injuries using atomic force microscopy-based indentation measurements. Unlike CNS tissue, PNS tissue significantly stiffened after both types of tissue damage, likely mainly due to an increase in collagen I levels. Schwann cells, which crucially support PNS regeneration, became more motile and proliferative on stiffer substrates in vitro, suggesting that changes in tissue stiffness may play a key role in facilitating or impeding nervous system regeneration.

neuroscience↗

bioRxiv2022

3D Bioelectronics with a Remodellable Matrix for Long-term Tissue Integration and Recording

Bioelectronics hold the key for understanding and treating disease. However, achieving stable, long-term interfaces between electronics and the body remains a challenge. Implantation of a bioelectronic device typically initiates a foreign body response, which can limit long-term recording and stimulation efficacy. Techniques from regenerative medicine have shown a high propensity for promoting integration of implants with surrounding tissue, but these implants lack the capabilities for the sophisticated recording and actuation afforded by electronics. Combining these two fields can achieve the best of both worlds. Here, we show the construction of a hybrid implant system for creating long-term interfaces with tissue. We create implants by combining a microelectrode array with a bioresorbable and remodellable gel. These implants are shown to produce a minimal foreign body response when placed into musculature, allowing us to record long-term electromyographic signals with high spatial resolution. This device platform drives the possibility for a new generation of implantable electronics for long-term interfacing.

bioengineering↗

bioRxiv2019

Mechanical matching of implant to host minimises foreign body reaction

Medical implants offer a unique and powerful therapeutic approach in many areas of medicine. However, their lifetime is often limited as they may cause a foreign body reaction (FBR) leading to their encapsulation by scar tissue1-4. Despite the importance of this process, how cells recognise implanted materials is still poorly understood5, 6. Here, we show how the mechanical mismatch between implants and host tissue leads to FBR. Fibroblasts and macrophages, which are both crucially involved in mediating FBR, became activated when cultured on materials just above the stiffness of healthy tissue. Coating stiff implants with a thin layer of hydrogel or silicone with a tissue-like elastic modulus ([~]20 kPa in subcutaneous and [~]2 kPa in peripheral nerve implants) or softer significantly reduced inflammation and fibrosis three months after implantation. Materials stiffer than the host tissue led to nuclear localisation of the mechanosensitive transcriptional regulator YAP in neighbouring cells in vivo, confirming mechanotransduction. The alleviation of FBR by soft coatings not exceeding the stiffness of the host tissue provides a strategy to achieve long-term implant stability without extensive modification of current implant manufacturing techniques, facilitating clinical translation.

bioengineering↗