Naturally-derived proteins, such as collagen, elastin, fibroin, and gelatin (denatured collagen) hold a remarkable promise for tissue engineering and regenerative medicine. Gelatin methacryloyl (GelMA), synthesized from the methacryloyl modification of gelatin, mimicking the structure of extracellular matrix, has widely been used as a universal multi-responsive scaffold for a broad spectrum of applications, spanning from cell therapy to bioprinting and organoid development. Despite the widespread applications of GelMA, coupled stiffness and porosity has inhibited its applications in 3D cellular engineering wherein a stiff scaffold with large pores is demanded (e.g.,
Peripheral nerve interfaces (PNIs) record and/or modulate neural activity of nerves, which are responsible for conducting sensory-motor information to and from the central nervous system, and for regulating the activity of inner organs. PNIs are used both in neuroscience research and in therapeutical applications such as precise closed-loop control of neuroprosthetic limbs, treatment of neuropathic pain and restoration of vital functions (e.g. breathing and bladder management). Implantable interfaces represent an attractive solution to directly access peripheral nerves and provide enhanced selectivity both in recording and in stimulation, compared to their non-invasive counterparts. Nevertheless, the long-term functionality of implantable PNIs is limited by tissue damage, which occurs at the implant-tissue interface, and is thus highly dependent on material properties, biocompatibility and implant design. Current research focuses on the development of mechanically compliant PNIs, which adapt to the anatomy and dynamic movements of nerves in the body thereby limiting foreign body response. In this paper, we review recent progress in the development of flexible and implantable PNIs, highlighting promising solutions related to materials selection and their associated fabrication methods, and integrated functions. We report on the variety of available interface designs (intraneural, extraneural and regenerative) and different modulation techniques (electrical, optical, chemical) emphasizing the main challenges associated with integrating such systems on compliant substrates.
Activation of nociceptor sensory neurons by noxious stimuli both triggers pain and increases capillary permeability and blood flow to produce neurogenic inflammation 1 , 2 , but whether nociceptors also interact with the immune system remains poorly understood. Here we report a neurotechnology for selective epineural optogenetic neuromodulation of nociceptors and demonstrate that nociceptor activation drives both protective pain behavior and inflammation. The wireless optoelectronic system consists of sub-millimeter-scale light-emitting diodes embedded in a soft, circumneural sciatic nerve implant, powered and driven by a miniaturized head-mounted control unit. Photostimulation of axons in freely moving mice that express channelrhodopsin only in nociceptors resulted in behaviors characteristic of pain, reflecting orthodromic input to the spinal cord. It also led to immune reactions in the skin in the absence of inflammation and potentiation of established inflammation, a consequence of the antidromic activation of nociceptor peripheral terminals. These results reveal a link between nociceptors and immune cells, which may have implications for the treatment of inflammation.
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