Mimicking Neuroplasticity in a Hybrid Biopolymer Transistor by Dual Modes Modulation

Neuromorphic computing systems that are capable of parallel information storage and processing with high area and energy efficiencies, offer important opportunities for future storage systems and in‐memory computing. Here, it is shown that a carbon dots/silk protein (CDs/silk) blend can be used as a light‐tunable charge trapping medium to fabricate an electro‐photoactive transistor synapse. The synaptic device can be optically operated in volatile or nonvolatile modes, ensuring concomitant short‐term and long‐term neuroplasticity. The synaptic‐like behaviors are attributed to the photogating effect induced by trapped photogenerated electrons in the hybrid CDs/silk film which is confirmed with atomic force microscopy based electrical techniques. In addition, system‐level pattern recognition capability of the synaptic device is evaluated by a single‐layer perceptron model. The remote optical operation of neuromorphic architecture provides promising building blocks to complete bioinspired photonic computing paradigms.     

Enhanced Structural Stability and Performance Durability of Bulk Heterojunction Photovoltaic Devices Incorporating Metallic Nanoparticles

Despite the progress on organic photovoltaic (OPV) performance, the photoactive layer degradation during prolonged solar illumination is still a major obstacle. In this work, an approach to mitigate the degradation pathway related to structural/morphological changes of the photoactive layer occurring upon continuous illumination in air is presented. It is shown, for the first time, that the incorporation of Ag nanoparticles in poly(3‐hexylthiophene) (P3HT) and [6‐6]‐phenyl‐C61‐butyric acid methyl ester bulk heterojunction (BHJ) leads to improved structural and morphological properties of the composite BHJ solar cells and to better photovoltaic (PV) stability after long periods of continuous illumination. This is evidenced by an original approach based on joint in‐situ time‐resolved X‐ray and atomic force microscopy monitoring. Besides the structural stability improvement and reduced photodegradation rate, it is shown that the composite blends exhibit superior PV performance compared to the pristine BHJs. It can be postulated that the incorporation of metallic nanoparticles in the BHJ leads to a dual enhancement, a plasmon absorption mediated effect, causing improved initial cell efficiency, and a structural stability effect giving rise to reduced degradation rate upon prolonged illumination. The results are in favor of the exploitation of polymer–nanoparticle composites as a promising approach to mitigate the aging effects in OPVs.     

Supertough Hybrid Hydrogels Consisting of a Polymer Double‐Network and Mesoporous Silica Microrods for Mechanically Stimulated On‐Demand Drug Delivery

Despite their potential in various fields of bioapplications, such as drug/cell delivery, tissue engineering, and regenerative medicine, hydrogels have often suffered from their weak mechanical properties, which are attributed to their single network of polymers. Here, supertough composite hydrogels are proposed consisting of alginate/polyacrylamide double‐network hydrogels embedded with mesoporous silica particles (SBA‐15). The supertoughness is derived from efficient energy dissipation through the multiple bondings, such as ionic crosslinking of alginate, covalent crosslinking of polyacrylamide, and van der Waals interactions and hydrogen bondings between SBA‐15 and the polymers. The superior mechanical properties of these hybrid hydrogels make it possible to maintain the hydrogel structure for a long period of time in a physiological solution. Based on their high mechanical stability, these hybrid hydrogels are demonstrated to exhibit on‐demand drug release, which is controlled by an external mechanical stimulation (both in vitro and in vivo). Moreover, different types of drugs can be separately loaded into the hydrogel network and mesopores of SBA‐15 and can be released with different speeds, suggesting that these hydrogels can also be used for multiple drug release.     

Graphene Intermediate Layer in Tandem Organic Photovoltaic Cells

One strategy to harvest wide spectral solar energy is to stack different bandgap materials together in a tandem solar cell. Here, it is demonstrated that CVD grown graphene film can be employed as intermediate layer (IML) in tandem solar cells. Using MoO₃‐modified graphene IML, a high open circuit voltage (V_oc) of 1 V and a high short‐circuit current density (J_sc) of 11.6 mA cm^‐2 could be obtained in series and parallel connection, respectively, in contrast to a V_oc of 0.58 V and J_sc of 7.6 mA cm^‐2 in single PV cell. The value of V_oc (J_sc) in the tandem cell is very close to the sum of V_oc (J_sc) attained from two single subcells in series (parallel), which confirms good ohmic contact at the photoactive layer/MoO₃‐modified graphene interface. Work function engineering of the graphene IML with metal oxide is essential to ensure good charge collection from both subcells.     

Injectable Hydrogels with In Situ Double Network Formation Enhance Retention of Transplanted Stem Cells

Stem cell transplantation via direct injection is a minimally invasive strategy being explored for treatment of a variety of injuries and diseases. Injectable hydrogels with shear moduli <50 Pa can mechanically protect cells during the injection process; however, these weak gels typically biodegrade within 1–2 weeks, which may be too fast for many therapeutic applications. To address this limitation, an injectable hydrogel is designed that undergoes two different physical crosslinking mechanisms. The first crosslinking step occurs ex vivo through peptide‐based molecular recognition to encapsulate cells within a weak gel that provides mechanical protection from injection forces. The second crosslinking step occurs in situ to form a reinforcing network that significantly retards material biodegradation and prolongs cell retention time. Human adipose‐derived stem cells are transplanted into the subcutaneous space of a murine model using hand‐injection through a 28‐gauge syringe needle. Cells delivered within the double‐network hydrogel are significantly protected from mechanical damage and have significantly enhanced in vivo cell retention rates compared to delivery within saline and single network hydrogels. These results demonstrate that in situ formation of a reinforcing network within an already existing hydrogel can greatly improve transplanted cell retention, thereby enhancing potential regenerative medicine therapies.     

Injectable Collagen–Genipin Gel for the Treatment of Spinal Cord Injury: In Vitro Studies

Spinal cord injury (SCI) often results in a cavitary lesion, contained within the dura, which involves only a portion of the cord. Injectable biopolymers are an attractive treatment option for SCI to re‐establish cell migratory pathways within the lesion while minimizing the collateral damage attendant to an open surgical procedure. In this study we evaluate a thermoresponsive soluble collagen gel incorporating genipin, an amine reactive covalent cross‐linker with low cytotoxicity and fluorogenic attributes. Unlike previous studies, genipin is being investigated as an in situ covalent cross‐linker that will continue to act on the gel after injection. Physical characterization studies show that the addition of genipin provides control over the mechanical and degradative behavior of the gel, to meet design specifications of an injectable material for neural tissues. Additionally, an improved in situ assay to predict the extent of cross‐linking reaction is investigated. Encapsulation of mesenchymal stem cells (MSCs) in collagen–genipin gels show the gels support cell viability and proliferation, and thus serve as a cell delivery vehicle. Neural stem cells are found to be more sensitive to genipin, with respect to toxicity, as compared to MSCs. From our studies, 0.25‐0.5 mM is an appropriate genipin concentration to use for an in situ forming scaffold capable of delivering cells and therapeutic agents.     

Photopicking: In Situ Approach for Site‐Specific Attachment of Single Multiprotein Nanoparticles to Atomic Force Microscopy Tips

Ligand–receptor interactions are fundamental in life sciences and include hormone–receptor, protein–protein, pathogen–host, and cell–cell interactions, among others. Atomic force microscopy (AFM) proved to be invaluable for scrutinizing ligand–receptor interactions at the single molecular level. Basically, a ligand is attached to the AFM tip while its cognate receptor is immobilized on a surface or vice versa, and interactions are studied following triggered ligand–receptor binding. However, with rising biological complexity it becomes increasingly challenging to attach a single intact biomolecule to the tip and ensure interaction‐specific orientation. This study presents a novel strategy of inducible in situ tip functionalization with complex multiprotein nanoparticles exemplified by viral capsids, termed photopicking. It ensures a firm attachment of single 125 nm large capsids to the tip. Specific orientation is attained by weak immunosorption of capsids to the substrate and strong photoinducible covalent cross‐linking to the tip. Validation of the tip functionalization success is immediate in situ. The versatility of the strategy is further demonstrated on 20–60 nm large amino‐modified nanoparticles. In conclusion, considering the size range of the tested biomolecules, the presented strategy is applicable to viruses, viral particles, cellular organelles, multiprotein ligands/receptors, and therapeutic nanoparticles, among others. It therefore opens up exciting new avenues in broad biomedical research fields.     

Organic Photovoltaic Sensors for Photocapacitive Stimulation of Voltage‐Gated Ion Channels in Neuroblastoma Cells

Organic semiconductors are emerging as promising candidates for novel electrically self‐sufficient photovoltaic prosthetics for neurostimulation, especially for restoration of light sensitivity in degenerate retina. Considering future applications, it is essential to gain fundamental insight into the signaling mechanisms at the organic photosensor–electrolyte–neuron interface. Particularly, targeting voltage‐gated ion channels by a pure photocapacitive stimulation is a preferred therapeutic approach as it avoids redox reactions involved in Faradaic charge injection. The present study investigates whether single neuroblastoma (N2A) cells, grown on a photosensor based on a small molecular squaraine:fullerene photoactive layer blend, optionally covered with silicon dioxide, can be activated by photocapacitive stimulation. Indeed, upon pulsed illumination, a rapid transient photocurrent strongly depolarizes the membrane potential and subsequently activates fast‐responding voltage‐gated sodium channels. The dielectric top coating on the organic layer ensures sufficient capacitive charge injection efficiency while maintaining the rapid response of the device. Due to the high irradiance level required for photocapacitive stimulation, another slower, independent, and unintended, nonelectrical signaling pathway is identified. This activates voltage‐gated potassium channels, presumably by photothermal effects. The present study provides the basis for further improvements on standalone photovoltaic neurostimulating platforms based on organic photoactive layers.     

Interpenetrated Gel Polymer Binder for High‐Performance Silicon Anodes in Lithium‐ion Batteries

Silicon has attracted ever‐increasing attention as a high‐capacity anode material in Li‐ion batteries owing to its extremely high theoretical capacity. However, practical application of silicon anodes is seriously hindered by its fast capacity fading as a result of huge volume changes during the charge/discharge process. Here, an interpenetrated gel polymer binder for high‐performance silicon anodes is created through in‐situ crosslinking of water‐soluble poly(acrylic acid) (PAA) and polyvinyl alcohol (PVA) precursors. This gel polymer binder with deformable polymer network and strong adhesion on silicon particles can effectively accommodate the large volume change of silicon anodes upon lithiation/delithiation, leading to an excellent cycling stability and high Coulombic efficiency even at high current densities. Moreover, high areal capacity of ～4.3 mAh/cm² is achieved based on the silicon anode using the gel PAA–PVA polymer binder with a high mass loading. In view of simplicity in using the water soluble gel polymer binder, it is believed that this novel binder has a great potential to be used for high capacity silicon anodes in next generation Li‐ion batteries, as well as for other electrode materials with large volume change during cycling.     

High‐Performance Phototransistors Based on Single‐Crystalline n‐Channel Organic Nanowires and Photogenerated Charge‐Carrier Behaviors

The photoelectronic characteristics of single‐crystalline nanowire organic phototransistors (NW‐OPTs) are studied using a high‐performance n‐channel organic semiconductor, N,N′‐bis(2‐phenylethyl)‐perylene‐3,4:9,10‐tetracarboxylic diimide (BPE‐PTCDI), as the photoactive layer. The optoelectronic performances of the NW‐OPTs are analyzed by way of their current–voltage (I–V) characteristics on irradiation at different wavelengths, and comparison with corresponding thin‐film organic phototransistors (OPTs). Significant enhancement in the charge‐carrier mobility of NW‐OPTs is observed upon light irradiation as compared with when performed in the dark. A mobility enhancement is observed when the incident optical power density increases and the wavelength of the light source matches the light‐absorption range of the photoactive material. The photoswitching ratio is strongly dependent upon the incident optical power density, whereas the photoresponsivity is more dependent on matching the light‐source wavelength with the maximum absorption range of the photoactive material. BPE‐PTCDI NW‐OPTs exhibit much higher external quantum efficiency (EQE) values (≈7900 times larger) than thin‐film OPTs, with a maximum EQE of 263 000%. This is attributed to the intrinsically defect‐free single‐crystalline nature of the BPE‐PTCDI NWs. In addition, an approach is devised to analyze the charge‐transport behaviors using charge accumulation/release rates from deep traps under on/off switching of external light sources.     

A Gene Therapy Technology‐Based Biomaterial for the Trigger‐Inducible Release of Biopharmaceuticals in Mice

Gene therapy scientists have developed expression systems for therapeutic transgenes within patients, which must be seamlessly integrated into the patient's physiology by developing sophisticated control mechanisms to titrate expression levels of the transgenes into the therapeutic window. However, despite these efforts, gene‐based medicine still faces security concerns related to the administration of the therapeutic transgene vector. Here, molecular tools developed for therapeutic transgene expression can readily be transferred to materials science to design a humanized drug depot that can be implanted into mice and enables the trigger‐inducible release of a therapeutic protein in response to a small‐molecule inducer. The drug depot is constructed by embedding the vascular endothelial growth factor (VEGF₁₂₁) as model therapeutic protein into a hydrogel consisting of linear polyacrylamide crosslinked with a homodimeric variant of the human FK‐binding protein 12 (F_M), originally developed for gene therapeutic applications, as well as with dimethylsuberimidate. Administrating increasing concentrations of the inducer molecule FK506 triggers the dissociation of F_M thereby loosening the hydrogel structure and releasing the VEGF₁₂₁ payload in a dose‐adjustable manner. Subcutaneous implantation of the drug depot into mice and subsequent administration of the inducer by injection or by oral intake triggers the release of VEGF₁₂₁ as monitored in the mouse serum. This study is the first demonstration of a stimuli‐responsive hydrogel that can be used in mammals to release a therapeutic protein on demand by the application of a small‐molecule stimulus. This trigger‐inducible release is a starting point for the further development of externally controlled drug depots for patient‐compliant administration of biopharmaceuticals.     

Complexation‐Induced Biomimetic Long Range Fibrous Orientation in a Rigid‐Flexible Block Copolymer Thermogel

The orientation of the organofibrous structure plays an important role not only in the biomineralization process but also in the extracellular matrix (ECM) of articular cartilage by providing cells with biomechanical cues. Here, it is reported that a long range nanofibrous orientation can be realized by a self‐assembling ionic complex between (+)‐charged amphiphilic peptide block copolymers with a rigid‐flexible block structure (polyalanine‐PLX‐polyalanine; PA‐PLX‐PA) and (‐)‐charged hyaluronic acid (HA). A biomimetic 3D culture system encapsulating chondrocytes is formed by a temperature‐sensitive sol‐to‐gel transition of the PA‐PLX‐PA/HA complex aqueous solution, which provides a compatible microenvironment for the cells. The cell proliferation and biomarker expression for articular cartilage are significantly improved in the PA‐PLX‐PA/HA complex system relative to the PA‐PLX‐PA or the commercially available Matrigel systems. In particular, noticeable cell clustering is observed in the PA‐PLX‐PA/HA complex system with the long range nanofibrous structure. This research suggests a new method for developing a nanofibrous structure using an amphiphilic peptide block copolymer and demonstrates its potential uses as a unique biomimetic cell‐culture matrix.     

A Multifunctional Nanodevice Capable of Imaging,Magnetically Controlling,and In Situ Monitoring Drug Release

The multifunctional nanodevice described here integrates nanoscaled imaging, targeting, and controlled drug delivery, as well as the capability to monitor, in situ, the amount of drug released from the nanodevice with single‐cell resolution. The nanodevice is composed of a polymer core/single‐crystal iron oxide shell nanostructure bonded to a quantum dot. It shows outstanding release and retention characteristics via an external on/off manipulation of a high‐frequency magnetic field. Upon magnetic stimulation, the single‐crystal iron oxide shell demonstrates formation of nanometer‐sized polycrystal domains of varying orientation. This allows a variation between retention and slow release of the drug. Further stimulation causes permanent rupturing of the shell, causing release of the drug in a burst‐like manner. The quantum dot bonded to the nanodevice provides optical information for in situ monitoring of the drug release through use of a magnetic field. Remote control drug release from the nanodevice in a cancerous cell line (HeLa) was successfully accomplished using the same induction scenario. When nanodevices equipped with quantum dots are taken into cancerous cells, they are able to provide real‐time drug dose information through a corresponding variation in emission spectrum. The nanodevice designed in this study has achieved its potential as a cell‐based drug‐delivery system for therapeutic applications.     

Enhanced Osteoblast Adhesion to Epoxide‐Functionalized Surfaces

As an alternative to expensive extracellular matrix (ECM) proteins generally applied as coatings in Petri dishes used for cell binding, an innovative system based on epoxide‐functionalized monolayers capable of protein binding is proposed. Since cells bind to material surfaces through proteins, protein‐binding surfaces should also promote cell binding. Here we investigate how the cell‐binding properties of an epoxide‐functionalized surface compares with ECM protein gel coated surfaces and tissue culture polystyrene control surfaces. Glass surfaces are functionalized with glycidoxypropyltriethoxysilane (GOPS), which results in an epoxide‐functionalized surface capable of binding proteins through an epoxide–amine reaction. Advancing contact angle measurements and atomic force microscopy measurements confirm the formation of a homogeneous GOPS monolayer. This monolayer is micropatterned with fluorescein‐labeled ECM protein gel by microcontact printing (µCP). Confocal laser scanning microscopy (CLSM) shows accurately transferred ECM protein gel micropatterns. Osteoblasts that are seeded on these micropatterned substrates show a clear preference for adhering to the epoxide‐functionalized areas. The morphology of these cultured osteoblasts is needle‐like with high aspect ratios. As controls, osteoblasts are cultured on GOPS‐functionalized surfaces, unstructured ECM protein gel surfaces, and tissue culture polystyrene (TCPS). The GOPS surfaces demonstrate a drastic increase in cell adhesion after 2 h, whilst the other tests show no adverse effects of this surface on the osteoblasts as compared to ECM and TCPS. CLSM shows healthy cell morphologies on each surface. It is demonstrated for the first time that epoxide groups outperform ECM protein gel in cell adhesion, thereby providing new routes for cost‐effective coatings that improve biocompatibility as well as exciting, new methodologies to control and direct cell adhesion.     

User‐Friendly Universal and Durable Subcellular‐Scaled Template for Protein Binding: Application to Single‐Cell Patterning

A new method for subcellular‐sized protein patterning on a SiOx substrate is demonstrated by dip‐pen nanolithography printed aldehyde‐terminated alkylsilane template. The aldehyde‐silane template is stable and durable; for example, subcellular scaled IgG protein array can be obtained using one‐year old aldehyde‐silane template. Moreover, single cell patterning is successfully carried out by extracellular material (ECM) protein microarray and nanoarray fabricated on an aldehyde‐silane template. With more than half of chance, single‐ or double‐cells are successfully attached on fibronectin protein nanoarrays in 21 × 21 μm ² (7 × 7 dot array) and 42 × 42 μm² (14 × 14 dot array). The fibronectin nanoarray with small area (21 × 21 μm²) shows the more rate of single cell attachment. Therefore, it is also demonstrated that cell patterning can be controlled by adjusting the nanostructure of ECM materials.     

Effective Codelivery of lncRNA and pDNA by Pullulan‐Based Nanovectors for Promising Therapy of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers. Maternally expressed gene 3 (MEG3, one kind of long noncoding RNA [lncRNA]) can act as a tumor suppressor and regulate P53 target gene expression. However, lncRNA MEG3 demonstrates relatively low or no expression in human HCC. This study provides a promising concept to codeliver lncRNA and pDNA for cancer therapy. As proof‐of‐concept, the pcDNA‐MEG3 and pcDNA‐P53 plasmids‐condensed nanocomplexes with the liver‐targeting polycation gene vector, pullulan‐based ethanolamine‐modified poly(glycidyl methacrylate) (denoted as PuPGEA), are proposed to codeliver lncRNA and pDNA to treat HCC. Pullulan‐containing nanovectors are shown to be able to effectively mediate gene delivery in liver cells. To assess gene delivery performances of PuPGEA, a series of assays such as in vitro gene transfection, HCC cell proliferation, colony formation, migration, matrigel transwell assays, and in vivo xenograft animal models are carried out. The codelivery system with PuPGEA/(MEG3+P53) nanocomplexes demonstrates additive effects in suppressing HCC compared to PuPGEA/MEG3 or PuPGEA/P53 nanocomplexes alone. These results suggest that codelivery of lncRNA and pDNA by polycation nanovectors is a promising method to treat cancers.     

Titrating the expression of a Gi protein-coupled receptor using an ecdysone-inducible system in CHO-K1 cells.

Changes in receptor density are often associated with pathological conditions. For example, high levels of the G protein-coupled somatostatin receptor, sst2, have been detected in a number of malignant cell types, a characteristic feature that is routinely utilised as a diagnostic tool. However, how the increased receptor expression affects cellular function through alterations in G protein-coupling or changes in the intensity or duration of activated signalling pathways is poorly understood. The current report details the use of an ecdysone-inducible expression system in CHO-K1 cells, whereby the consequence of modulating the level of human sst2 receptor expression on specific transduction events can be examined. A time- and concentration-dependent induction of sst2 receptor expression was attained by exposure of cells to the ecdysteroid-inducing agent, muristerone A (MuA). Increases in sst2 receptor expression were determined by immunoassay, immunoblotting and immunocytochemical analysis. Maximal sst2 receptor expression was obtained after treatment of cells with 7 microM MuA for 24 h. Functionality of the sst2 receptor was assessed by immunoblot analysis of phosphorylated forms of MAP kinase. Following receptor activation, time-dependent increases in the level of MAP kinase phosphorylation were shown to correlate with the degree of sst2 receptor induction. Confirmation of receptor activation was determined by visualisation of ligand-induced redistribution of sst2 receptors from the plasma membrane to discrete intracellular compartments. However, in a series of further studies, both immunocytochemical and fluorescence-activated cell sorting (FACS) analyses demonstrated that over a prolonged period, stable receptor expression could not be maintained in CHO-K1 cells using this expression system. Thus, routine analysis of the sst2 receptor expressing cell population is required to derive comparable results between assays, especially when some assays provide information from the whole cell population whilst others are based at the single cell level. On the basis of these observations we conclude that, providing such quality control measurements are taken, the ecdysone inducible expression system is a useful tool to modulate functional sst2 receptor expression in an in vitro environment over short time periods.     

Supramolecular Chemistry in Molten Sulfur: Preorganization Effects Leading to Marked Enhancement of Carbon Nitride Photoelectrochemistry

Here, a new method for enhancing the photoelectrochemical properties of carbon nitride thin films by in situ supramolecular‐driven preorganization of phenyl‐contained monomers in molten sulfur is reported. A detailed analysis of the chemical and photophysical properties suggests that the molten sulfur can texture the growth and induce more effective integration of phenyl groups into the carbon nitride electrodes, resulting in extended light absorption alongside with improved conductivity and better charge transfer. Furthermore, photophysical measurements indicate the formation of sub‐bands in the optical bandgap which is beneficial for exciton splitting. Moreover, the new bands can mediate hole transfer to the electrolyte, thus improving the photooxidation activity. The utilization of high temperature solvent as the polymerization medium opens new opportunities for the significant improvement of carbon nitride films toward an efficient photoactive material for various applications.     

Composite Three‐Dimensional Woven Scaffolds with Interpenetrating Network Hydrogels to Create Functional Synthetic Articular Cartilage

The development of synthetic biomaterials that possess mechanical properties mimicking those of native tissues remains an important challenge to the field of materials. In particular, articular cartilage is a complex nonlinear, viscoelastic, and anisotropic material that exhibits a very low coefficient of friction, allowing it to withstand millions of cycles of joint loading over decades of wear. Here, a three‐dimensionally woven fiber scaffold that is infiltrated with an interpenetrating network hydrogel can build a functional biomaterial that provides the load‐bearing and tribological properties of native cartilage. An interpenetrating dual‐network “tough‐gel” consisting of alginate and polyacrylamide was infused into a porous three‐dimensionally woven poly(?‐caprolactone) fiber scaffold, providing a versatile fiber‐reinforced composite structure as a potential acellular or cell‐based replacement for cartilage repair.     

Conditional DNA‐Protein Interactions Confer Stimulus‐Sensing Properties to Biohybrid Materials

Interactive materials that specifically respond to environmental stimuli hold high promise as energy‐autonomous sensors and actuators in biomedicine, analytics or microsystems engineering. However, the implementation of materials specifically responsive to a given small molecule has so far been hampered by a lack of generically applicable stimulus sensors. In this study, a novel and likely general strategy for the synthesis of biohybrid materials with desired stimulus specificity is established. The strategy is based on allosterically regulated DNA‐binding proteins, a conserved protein family that has evolved in prokaryotes to sense and respond to most diverse molecules in order to enable bacterial survival in a changing environment. The novel hydrogel design concept is demonstrated with the example of single‐chain TetR, a protein that binds the tetO DNA motif and dissociates thereof in the presence of the antibiotic tetracycline. Therefore, linear polyacrylamide is crosslinked via the TetR/tetO interaction to a biohybrid material that can subsequently be dissolved by tetracycline in a dose‐dependent manner. This drug‐induced dissolution is applied for the adjustable release of the cytokine interleukin 4 in a tetracycline‐dependent manner. The design concept developed in this study might serve as a blueprint for the synthesis of biohybrid materials responsive to drugs, metabolites or toxins by replacing TetR/tetO with another protein/DNA pair showing the desired stimulus specificity.