Schematic illustrating the components of a MARTEENI device. (A) Design of a functional MARTEENI device implanted within a nerve defect. The device includes a hydrogel wrapped with decellularized small intestine submucosa (SIS) and electrodes embedded within a polyimide substrate that is further connected to a printed circuit board (PCB) for electrical connectivity to the device. (B) Cross-sectional view of polyimide threads encapsulated within a non-templated hydrogel. (C) Cross-sectional view of polyimide threads encapsulated within a magnetically templated hydrogel with microchannels aligned in the same direction as the threads. (D) Schematic of the MARTEENI hydrogel templating process using magnetic alginate microparticles (MAMs).
Evaluation of magnetically templated hydrogel physical properties. (A) Quasistatic mechanical measurements demonstrate decreased instantaneous and steady-state moduli following magnetic templating at all GMHA concentrations (n=6). Green bar depicts mechanical stiffness range for fresh rat sciatic nerve tissue. Orthogonal projections of 10 mg/ml GMHA-Col templated hydrogels (B) after hydrogel fabrication, before MAM dissolution and (C) after MAM dissolution, demonstrating open channels at very low hydrogel stiffnesses. (D) MARTEENI device visualized with polyimide threads (green) surrounded by open microchannels backfilled with fluorescent dextran (red). Scale bar = 200 µm. 2-way ANOVA, * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001.Researchers at the University of Florida have developed a magnetically aligned hydrogel scaffold and polymer-based electrode improves the interface with nerve tissue [Kasper et al., Biomaterials 279 (2021) 121212, https://doi.org/10.1016/j.biomaterials.2021.121212].
Nerve damage can cause debilitating pain, loss of sensation, reduced movement and, in the worst cases, require amputation. While prosthetic limb technology has become significantly better over the last 20 years, providing amputees with some basic motor control, the nerve interface technology needed to provide more sensitive movement has not progressed as far. Research is currently focused on direct interfacing between prostheses and the nervous system via internal implanted neural inputs. However, typical electrode materials elicit an inflammatory, foreign-body response. To overcome these shortcomings, the team, led collaboratively by Christine E. Schmidt, Jack W. Judy, Carlos Rinaldi-Ramos and Kevin J. Otto, combined regenerative approaches – to encourage tissue regrowth and repair – with neural interface technologies that connect with prostheses.
“[Our approach aims to] provide amputees with greater control of their prosthetics by increasing the number of nerve cells interacting with the electrical sites, [giving] more control over the ability of amputees to feel their environment,” say Schmidt and first author Mary Kasper.
The researchers designed a magnetically aligned regenerative tissue-engineered electronic nerve interface (MARTEENI) based on polyimide threads, which act as microelectrodes interfacing with axons, encased within a hydrogel scaffold. Magnetic alginate microparticles create aligned, linear channels in the hydrogel that mimic the structure of natural tissue, promoting the proliferation of peripheral nerve cells and providing channels to direct the growth of axons in the vicinity of the electrodes. Unlike other interface materials, such as tungsten and silicon, the hydrogel matches much more closely the stiffness and structure of native neural tissue.
“We are able to change the stiffness of our scaffold by changing the concentration of the polymer and by introducing microarchitecture through magnetic particle templating,” explain Schmidt and Kasper. “By modulating the stiffness to the range of native nerve tissue with the introduction of microarchitecture, we can promote a higher density and greater depth of cells migrating into the resulting scaffold.”
Nerve-damaged rats implanted with prototype non-functional MARTEENI devices showed undisrupted tissue remodeling and nerve regeneration over 6-12 weeks. Although the implants did induce foreign-body responses, these are similar or less than those seen with traditional neural interfaces.
The approach is sufficiently promising, believe the researchers, to warrant the implantation of fully functional MARTEENI devices to test the efficacy of neural recovery over longer time periods and assess the ability to record electrophysiological information and provide stimulation.
“This work bridges the space between neural interfacing and tissue engineering,” Schmidt and Kasper point out. “Future work could include the incorporation of growth factors or drugs that could aid in mitigating foreign body response.”