The need for advanced materials in emerging technologies such as tissue engineering has prompted increased research to produce novel biodegradable polymers elastic in nature and mechanically compliant with the host tissue. We have developed a soft biodegradable elastomeric platform biomaterial created from citric acid, maleic anhydride, and 1,8-octanediol, poly(octamethylene maleate (anhydride) citrate) (POMaC), which is able to closely mimic the mechanical properties of a wide range of soft biological tissues. POMaC features a dual crosslinking mechanism, which allows for the option of the crosslinking POMaC using UV irradiation and/or polycondensation to fit the needs of the intended application. The material properties, degradation profiles, and functionalities of POMaC thermoset networks can all be tuned through the monomer ratios and the dual crosslinking mechanism. POMaC polymers displayed an initial modulus between 0.03 and 1.54 MPa, and elongation at break between 48% and 534% strain. In vitro and in vivo evaluation using cell culture and subcutaneous implantation, respectively, confirmed cell and tissue biocompatibility. POMaC biodegradable polymers can also be combined with MEMS technology to fabricate soft and elastic 3D microchanneled scaffolds for tissue engineering applications. The introduction of POMaC will expand the choices of available biodegradable polymeric elastomers. The dual crosslinking mechanism for biodegradable elastomer design should contribute to biomaterials science.

In this letter, we developed an integrated neural probe prototype for optogenetic stimulation by microscale light-emitting diode (μLED) and simultaneous recording of neural activities with microelectrodes on a single-polyimide platform. Optogenetics stimulates in vivo neural circuits with high-cellular specificity achieved by genetic targeting and precise temporal resolution by interaction of light-gated ion channels with optical beam. In our newly developed optrode probe, during optogenetic stimulation of neurons, continuous sensing of neuronal activities in vicinity of the activation site can provide feedback to stimulation or examine local responses in signal pathways. In the device, focusing the light from the μLED was achieved with an integrated photo-polymerized lens. The efficacy of the optrode for cortical stimulation and recording was tested on mice visual cortex neurons expressing channelrhodopsin-2. Stimulation intensity and frequency-dependent spiking activities of visual cortex were recorded. Our device has shown advantages over fiber-coupled laser-based optrode in terms of closed-loop integration, single-implant compactness and lower electrical power requirements, which would be clinically applicable for future prosthetic applications in personalized medicine.

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Biomimetic scaffolds that replicate the native architecture and mechanical properties of target tissues have been recently shown to be a very promising strategy to guide cellular growth and facilitate tissue regeneration. In this study, porous, soft, and elastic crosslinked urethane-doped polyester (CUPE) tissue engineered nerve guides were fabricated with multiple longitudinally oriented channels and an external non-porous sheath to mimic the native endoneurial microtubular and epineurium structure, respectively. The fabrication technique described herein is highly adaptable and allows for fine control over the resulting nerve guide architecture in terms of channel number, channel diameter, porosity, and mechanical properties. Biomimetic multichanneled CUPE guides were fabricated with various channel numbers and displayed an ultimate peak stress of 1.38 ± 0.22 MPa with a corresponding elongation at break of 122.76 ± 42.17 %, which were comparable to that of native nerve tissue. The CUPE nerve guides were also evaluated in vivo for the repair of a 1 cm rat sciatic nerve defect. Although histological evaluations revealed collapse of the inner structure from CUPE TENGs, the CUPE nerve guides displayed fiber populations and densities comparable with nerve autograft controls after 8 weeks of implantation. These studies are the first report of a CUPE-based biomimetic multichanneled nerve guide and warrant future studies towards optimization of the channel geometry for use in neural tissue engineering.

In this work, we have developed an integrated flexible implantable probe on a polyimide-film substrate for sensing neurotransmitters. The flexibility of the probe helps to prevent scar forming in tissues aiming for long-term in vivo monitoring. A micro Ag/AgCl reference electrode was integrated in the same probe with the Au/Cr or Pt/Cr working electrodes providing measurements without the need of a separate reference probe. Several electrode configurations have been considered and designed for implantation at various locations in the central nervous system. The prototype device for proof of principle was an enzyme-based electrochemical L-glutamate sensor using L-glutamate oxidase. A comparison between Au and Pt thin films was conducted by cyclic voltammetry to evaluate their performance as working electrodes. The L-glutamate oxidase was deposited on the working electrodes followed by a meta-Phenylenediamine electropolymerization process to improve the selectivity. The self-referencing technique was also utilized to enhance both the limit of detection and selectivity. The assembled sensors were calibrated and tested at various concentrations of L-glutamate with and without the presence of interfering molecules. The results showed good sensitivity and selectivity. In vivo animal tests were conducted to show the capability of detecting changes of electrochemical signals responding to graded peripheral somatosensory stimuli.