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Bioengineered "Living Electrodes" for Neuromodulation


Engineered axonal tracts for synaptic-based interface and modulation of neural circuitry



D. Kacy Cullen, James Harris, John Wolf, H. Isaac Chen, Douglas Smith, Mijail Serruya


Brain-machine interface (BMI) and neuromodulation devices provide means to record and stimulate the nervous system to treat neurological deficits and/or provide a communication platform with peripheral devices/ prosthetics.  However, these approaches are limited in that electrical stimulation is non-specific and because conventional electrodes are rigid and non-organic, there is an inflammatory foreign body response that diminishes the quality of the recording and stimulation over time.


Due to the limitations in existing approaches, the inventors developed the first living, biologically-based electrodes to provide a biocompatible and stable interface to probe and modulate the nervous system. The ‘living electrodes” are miniature hair-like hydrogel cylinders containing neuronal population(s) on one or both ends spanned by long axonal tracts within the interior lumen.


Upon microinjection, the axonal segment penetrates the brain to a prescribed depth for synaptic integration with local host neurons, with the neuronal cell body segment remaining on the brain surface where functional information is gathered and/or inputted.  The hydrogel encasement chaperones delivery into the brain but is gradually reabsorbed to leave only living axonal tracts within the brain, thus attenuating a chronic foreign body response. To date, the inventors have constructed axon-based living electrodes using a range of neuronal subtypes, including dopaminergic, GABAergic, and glutamatergic, each with differential capacity to stimulate and/or modulate neural circuitry based on the specificity uniquely afforded by synaptic integration.


Although living electrodes naturally integrate into the native neuronal network, they are ultimately computer controlled by optical, electrical, magnetic, or chemical means accessible using planar microarrays on the brain surface. As such, the living electrodes act as a natural, biological intermediary between an individual’s nervous system and superficial device(s). The neurological device market in 2016 achieved sales of $6,373 million with neurostimulation devices grossing $3,466 million growing at 5.2% per year from 2009-2016 (Global Data).





• Biologically-based neuromodulation in Parkinson’s disease patients

• Synaptic/neurotransmitter based inhibition to silence hyperexcitable circuits in epilepsy

• Chronic BMI applications by providing synaptic-based input from tactile sensors on advanced prosthetic limbs directly to sensory brain regions.


Stage of Development

• Optimized and validated micro-tissue engineering fabrication process

• Living electrode implantation survival, synaptic integration with host neurons, and electrophysiological activity demonstrated in rats

• Current in vivo efforts in rats focus on assessing efficacy for targeted, synaptic based modulation of neural circuitry

• Validation of techniques with a biomass suitable for clinical trials



• Unparalleled specificity, spatial density, and long-term fidelity in neural stimulation

• “Biohybrid” interface is a new paradigm for controlled modulation of neural activity to treat disease and injury

• Improve lives of patients with Parkinson’s disease, epilepsy, spinal cord inury, loss-of-limb, and complete paralysis.


Desired partnerships

• License

• Co-development

• Partnership with PENN startup company


Reference Media

Adewole et al., bioRxiv (2018)

doi: https://doi.org/10.1101/333526

Dhobale et al., J Neural Eng (2018)

doi: 10.1088/1741-2552/aac96d.

Serruya et al., Advanced Functional Materials (2018)

doi: 10.1002/adfm.201701183

Struzyna & Adewole et al., J Vis Exp (2017)

doi: 10.3791/55609

Adewole et al., Crit Rev Biomed Eng (2016)

doi: 10.1615/CritRevBiomedEng.2016017198

Harris et al., J Neurl Eng (2016)

doi: 10.1088/1741-2560/13/1/016019

Struzyna et al., Tissue Eng Part A (2015)

doi: 10.1089/ten.TEA.2014.0557



Intellectual Property

PCT/US2017/027705: filed 4/14/17


Download PDF



Docket #16-7712 


Cross Reference: Tissue Engineered Astrocyte Scaffolds for Neural Regeneration (Docket # 14-7154)

Patent Information:
Medical Devices
For Information, Contact:
Neal Lemon
Associate Director, PSOM Licensing Group
University of Pennsylvania
Daniel Kacy Cullen
James Harris
John Wolf
H. Isaac Chen
Douglas Smith
Mijail Serruya