Here, we report on the first systematic long-term study of fibroblast therapy in a mouse model for recessive dystrophic epidermolysis bullosa (RDEB), a severe skin-blistering disorder caused by loss-of-function of collagen VII. Intradermal injection of wild-type (WT) fibroblasts in >50 mice increased the collagen VII content at the dermal–epidermal junction 3.5- to 4.7-fold. Although the active biosynthesis lasted <28 days, collagen VII remained stable and dramatically improved skin integrity and resistance to mechanical forces for at least 100 days, as measured with a digital 3D-skin sensor for shear forces. Experiments using species-specific antibodies, collagen VII–deficient fibroblasts, gene expression analyses, and cytokine arrays demonstrated that the injected fibroblasts are the major source of newly deposited collagen VII. Apart from transitory mild inflammation, no adverse effects were observed. The cells remained within an area ≤10 mm of the injection site, and did not proliferate, form tumors, or cause fibrosis. Instead, they became gradually apoptotic within 28 days. These data on partial restoration of collagen VII in the skin demonstrate the excellent ratio of clinical effects to biological parameters, support suitability of fibroblast-based therapy approaches for RDEB, and, as a preclinical test, pave way to human clinical trials.

Optogenetic hearing restoration in rodents by LED-based multichannel optical cochlear implants provides improved spectral selectivity.

This study reports the realization of an optical cochlear implant (oCI) with optimized thermomechanical properties for optogenetic experiments. The oCI probe comprises 144 miniaturized light-emitting diodes (μLEDs) distributed along a bendable, 1.5-cm-long, 350-μm-wide and 26-μm-thick probe shaft, individually controlled via a n × p matrix interconnection. In contrast to our earlier approach based on polyimide (PI) and epoxy resin with different thermal expansion coefficients, the μLEDs and interconnecting wires are now embedded into a triple-layer stack of a single, biocompatible, and highly transparent epoxy material. The new material combination results in a pronounced reduction of thermomechanical bending in comparison with the material pair of the earlier approach. We developed a spin-coating process enabling epoxy resin layers down to 5 μm at thickness variations of less than 7% across the entire carrier wafer. We observed that the cross-linking of epoxy resin layers strongly depends on the spin-coating parameters which were found to be correlated to a potential separation of epoxy resin components of different densities. Furthermore, various metallization layers and corresponding adhesion promoting layers were investigated. We identified the combination of silicon carbide with a titanium-based metallization to provide the highest peeling strength, achieving an adhesion to epoxy improved by a factor of two. In order to obtain a high process yield, we established a stress-free implant release using the electrochemical dissolution of a sacrificial aluminum layer. The direct comparison of oCI probe variants using a single epoxy material and the combination of PI and epoxy resin revealed that the epoxy-resin-only probe shows minimal thermomechanical probe bending with a negligible hysteresis. The thermal probe characterization demonstrated that the temperature increase is limited to 1 K at μLED DC currents of up to 10 mA depending on the stimulation duration and the medium surrounding the probe. The optical output power and peak wavelengths of the new oCI variant were extracted to be 0.82 mW and 462 nm when operating the μLEDs at 10 mA, 10 kHz, and a duty cycle of 10%. The optical power corresponds to a radiant emittance of 407 mW/mm², sufficient for optogenetic experiments using channelrhodopsin-2.

Electrical cochlear implants (eCIs) partially restore hearing and enable speech comprehension to more than half a million users, thereby re‐connecting deaf patients to the auditory scene surrounding them. Yet, eCIs suffer from limited spectral selectivity, resulting from current spread around each electrode contact and causing poor speech recognition in the presence of background noise. Optogenetic stimulation of the auditory nerve might overcome this limitation as light can be conveniently confined in space. Here, we combined virus‐mediated optogenetic manipulation of cochlear spiral ganglion neurons (SGNs) and microsystems engineering to establish acute multi‐channel optical cochlear implant (oCI) stimulation in adult Mongolian gerbils. oCIs based on 16 microscale thin‐film light‐emitting diodes (μLEDs) evoked tonotopic activation of the auditory pathway with high spectral selectivity and modest power requirements in hearing and deaf gerbils. These results prove the feasibility of μLED‐based oCIs for spectrally selective activation of the auditory nerve.