Spatiotemporal Delivery Research Articles

Near-Infrared Photothermal Release of siRNA from the Surface of Colloidal Gold-Silver-Gold Core-Shell-Shell Nanoparticles Studied with Second-Harmonic Generation.

Photothermal release of oligonucleotides from the surface of plasmonic nanoparticles represents a promising platform for spatiotemporal controlled drug delivery. Here we demonstrate the use of novel gold-silver-gold core-shell-shell (CSS) nanoparticles to study the photothermal cleaving and release of micro-RNA (miRNA) mimics or small interfering RNA (siRNA) under nearinfrared (NIR) irradiation. The furan-maleimide-based Diels-Alder adduct cleaves thermally above 60 °C and is used to bind siRNA to the colloidal nanoparticle surface in water. We investigate the photothermal cleaving kinetics of siRNA under different NIR laser powers using surface-sensitive time-dependent second-harmonic generation (SHG) spectroscopy. The photothermal release of siRNA from the surface of CSS nanoparticles is significantly higher than that from the surface of gold nanoparticles (GNPs) under similar experimental conditions. These results demonstrate that plasmonic CSS nanoparticles with photothermal cleaving linkers have important potential applications for nanoparticle-based NIR-mediated drug-delivery systems.

Haptic Enchanters: Attachable and Detachable Vibrotactile Modules and Their Advantages.

This paper showcases attachable/detachable haptic modules, nicknamed haptic enchanters, by presenting their conceptual prototypes and quantifying their information transmission capacity. Haptic enchanters can be attached to ordinary devices and wearables to endow them with the ability of creating programmable haptic stimuli, thereby transforming them to effective haptic communication devices. In particular, our prototype enchanters are designed to localize vibrotactile stimulation to the neighborhood of attachment site, and this spatial isolation allows for effective spatiotemporal information delivery using multiple enchanters. We demonstrate that haptic enchanters enable very high capacity of information transfer (4.55-7.06 bits) for spatiotemporal vibration sequences rendered with two, three, and four enchanters. We also assert that haptic enchanters provide better user experiences by using location-enabled feedback in a game application than the whole-device feedback. These results instantiate the performance of haptic enchanters as effective and convenient communication accessories and their potential for applications.

Shear Containment of BDNF within Molecular Hydrogels Promotes Human Stem Cell Engraftment and Postinfarction Remodeling in Stroke

AbstractImproved control over spatiotemporal delivery of growth factors is needed to enhance tissue repair. Current methods are limited–requiring invasive procedures, poor tissue targeting, and/or limited control over dosage and duration. Incorporation into implantable biomaterials enables stabilized delivery and avoids burst release/fluctuating doses. Here, the physical forces of fibrils formed by self‐assembly of epitope‐containing peptides are exploited. This biomimetic hydrogel is loaded with neurotrophic factor BDNF via a shear‐induced gel–solution transition, unique to noncovalent hydrogels. This results in a biomaterial with three desirable features: a nanofibrillar scaffold, presentation of a laminin epitope, and slow release of BDNF. In a stroke‐injury model, synergistic actions of this trimodal strategy on the integration of transplanted human neural progenitor cells, and protection of peri‐infarct tissue are identified. These BDNF‐functionalized hydrogels promote the integration of transplanted human embryonic stem cell–derived neural progenitors–resulting in larger grafts with greater cortical differentiation, appropriate for neuronal replacement. Furthermore, BDNF promotes the infiltration of host endothelial cells into the graft to augment vascularization of the graft, and adjacent penumbra tissue. These findings demonstrate the benefits of multifaceted tissue‐specific hydrogels to provide biomimetics of the host tissue, while sustain protein delivery, to promote endogenous and graft‐derived tissue repair.

Physicochemical Analysis of DPPC and Photopolymerizable Liposomal Binary Mixture for Spatiotemporal Drug Release.

The development of a spatiotemporal drug delivery system with a long release profile, high loading efficiency, and robust therapeutic effects is still a challenge. Liposomal nanocarriers have secured a fortified position in the biomedical field over decades. Herein, liposomal binary mixtures of 1,2-dipalmitoyl- sn-glycero-3-phosphocholine (DPPC) and photopolymerizable 1,2-bis(10,12-tricosadiynoyl)- sn-glycero-3-phosphocholine (DC8,9PC) phospholipids were prepared for drug delivery applications. The diacetylenic groups of DC8,9PC produce intermolecular cross-linking following UV irradiation. Exposure of the liposomal mixture to 254 nm radiation induces a pore within the lipid bilayer, expediting the release of its entrapped 5,6-carboxyfluorescein dye. The dosage and rate of the released content are highly dependent on the number and size of the induced pore. Photochemical cross-linking studies at different exposure times were reported through the analysis of UV-visible spectrophotometry, nano differential scanning calorimetry, Fourier transform infrared spectroscopy, and Raman spectroscopy. The optimal irradiation time was established after 8 min of exposure, inducing lipid cross-linking with minimal oxidative degradation, which plays an essential role in the pathogenesis of numerous diseases due to the formation of primary and secondary oxidation products, accordingly reducing the encapsulated drug therapeutic level.

Microcapsule Technology for Controlled Growth Factor Release in Musculoskeletal Tissue Engineering.

Tissue engineering strategies have relied on engineered 3-dimensional (3D) scaffolds to provide architectural templates that can mimic the native cell environment. Among the several technologies proposed for the fabrication of 3D scaffold, that can be attractive for stem cell cultivation and differentiation, moulding or bioplotting of hydrogels allow the stratification of layers loaded with cells and with specific additives to obtain a predefined microstructural organization. Particularly with bioplotting technology, living cells, named bio-ink, and additives, such as biopolymer microdevices/nanodevices for the controlled delivery of growth factors or biosignals, can be organized spatially into a predesigned 3D pattern by automated fabrication with computer-aided digital files. The technologies for biopolymer microcarrier/nanocarrier fabrication can be strategic to provide a controlled spatiotemporal delivery of specific biosignals within a microenvironment that can better or faster address the stem cells loaded within it. In this review, some examples of growth factor-controlled delivery by biopolymer microdevices/nanodevices embedded within 3D hydrogel scaffolds will be described, to achieve a bioengineered 3D interactive microenvironment for stem cell differentiation. Conventional and recently proposed technologies for biopolymer microcapsule fabrication for controlled delivery over several days will also be illustrated and critically discussed.

Synthesis and evaluation of water soluble pH sensitive poly (vinyl alcohol)-doxorubicin conjugates

The accuracy of spatiotemporal control cargo delivery and release are primordial to enhance the therapeutic efficiency and decrease the undesirable effects, in this context a novel prodrug were developed based on biocompatible polyvinyl alcohol (PVA) substrate. PVA was conjugated to doxorubicin (PVA-DOX) via an acid-labile hydrazone linkage. PVA was first functionalized with acidic groups, then reacted with hydrazine hydrate to form an amide bond. The amine group of PVA hydrazide was linked to carbonyl group (C = O) of DOX to form a pH sensitive hydrazone bond. The molecular structure of the PVA-DOX was confirmed by FTIR, XPS, and 1H-NMR analysis methods. The degree of grafting were evaluated by TGA and confirmed by XPS, which reveals the successful bond attachment of DOX to PVA. Our findings confirm pH dependent DOX release from PVA-DOX prodrug with faster release rate in acidic environment (pH 5.0, pH 6.0) and slower release rate in neutral pH environment (pH 7.4). Compared to the primary DOX, our synthesized PVA-DOX conjugates could exhibit a promising therapeutic effect, high biocompatibility and zero premature release. The results prove the successful synthesis of PVA-DOX conjugates with high efficiency.

An Optogenetic Platform for Real-Time, Single-Cell Interrogation of Stochastic Transcriptional Regulation

SummaryTranscription is a highly regulated and inherently stochastic process. The complexity of signal transduction and gene regulation makes it challenging to analyze how the dynamic activity of transcriptional regulators affects stochastic transcription. By combining a fast-acting, photo-regulatable transcription factor with nascent RNA quantification in live cells and an experimental setup for precise spatiotemporal delivery of light inputs, we constructed a platform for the real-time, single-cell interrogation of transcription in Saccharomyces cerevisiae. We show that transcriptional activation and deactivation are fast and memoryless. By analyzing the temporal activity of individual cells, we found that transcription occurs in bursts, whose duration and timing are modulated by transcription factor activity. Using our platform, we regulated transcription via light-driven feedback loops at the single-cell level. Feedback markedly reduced cell-to-cell variability and led to qualitative differences in cellular transcriptional dynamics. Our platform establishes a flexible method for studying transcriptional dynamics in single cells.

Molecular Design and Medicinal Applications of Nano-Nitric Oxide Delivery Systems.

Nitric oxide (NO) plays important regulatory roles in a plethora of biological functions and thus holds tremendous potential to be exploited for clinical uses. However, the chemistries in the molecular design of nano-nitric oxide delivery systems is currently lacking. The overarching aim of this review is to provide the readers with the fundamentals that relate to the design of NO release molecules (NORMs), loading and releasing mechanism, as well as delivery of NORMs for nanotherapeutics. We conducted a thorough literature search on the design and synthesis of NORMs, as well as the current state-of-the-art NO compatible delivery platforms to address various clinical needs. N-diazeniumdiolate and S-nitrosothiol based NO molecules are among the most widely used NORMs for anti-cancer and anti-microbial applications. The innovative integration of these NORMs with cytocompatible organic and inorganic nanocarriers enabled controlled spatiotemporal delivery and release of NO at the targeted diseased sites. We have provided a comprehensive summary of the fundamental chemistries underpinning the molecular design of the NORMs and critically assessed the recent advancements of nano-NO delivery systems for advanced biomedical applications.

Instructive microenvironments in skin wound healing: Biomaterials as signal releasing platforms.

Skin wound healing aims to repair and restore tissue through a multistage process that involves different cells and signalling molecules that regulate the cellular response and the dynamic remodelling of the extracellular matrix. Nowadays, several therapies that combine biomolecule signals (growth factors and cytokines) and cells are being proposed. However, a lack of reliable evidence of their efficacy, together with associated issues such as high costs, a lack of standardization, no scalable processes, and storage and regulatory issues, are hampering their application. In situ tissue regeneration appears to be a feasible strategy that uses the body's own capacity for regeneration by mobilizing host endogenous stem cells or tissue-specific progenitor cells to the wound site to promote repair and regeneration. The aim is to engineer instructive systems to regulate the spatio-temporal delivery of proper signalling based on the biological mechanisms of the different events that occur in the host microenvironment. This review describes the current state of the different signal cues used in wound healing and skin regeneration, and their combination with biomaterial supports to create instructive microenvironments for wound healing.

Temporomandibular Joint Regenerative Medicine.

The temporomandibular joint (TMJ) is an articulation formed between the temporal bone and the mandibular condyle which is commonly affected. These affections are often so painful during fundamental oral activities that patients have lower quality of life. Limitations of therapeutics for severe TMJ diseases have led to increased interest in regenerative strategies combining stem cells, implantable scaffolds and well-targeting bioactive molecules. To succeed in functional and structural regeneration of TMJ is very challenging. Innovative strategies and biomaterials are absolutely crucial because TMJ can be considered as one of the most difficult tissues to regenerate due to its limited healing capacity, its unique histological and structural properties and the necessity for long-term prevention of its ossified or fibrous adhesions. The ideal approach for TMJ regeneration is a unique scaffold functionalized with an osteochondral molecular gradient containing a single stem cell population able to undergo osteogenic and chondrogenic differentiation such as BMSCs, ADSCs or DPSCs. The key for this complex regeneration is the functionalization with active molecules such as IGF-1, TGF-β1 or bFGF. This regeneration can be optimized by nano/micro-assisted functionalization and by spatiotemporal drug delivery systems orchestrating the 3D formation of TMJ tissues.

A Scalable Weight-Free Learning Algorithm for Regulatory Control of Cell Activity in Spiking Neuronal Networks.

Recent developments in neural stimulation and recording technologies are providing scientists with the ability of recording and controlling the activity of individual neurons in vitro or in vivo, with very high spatial and temporal resolution. Tools such as optogenetics, for example, are having a significant impact in the neuroscience field by delivering optical firing control with the precision and spatiotemporal resolution required for investigating information processing and plasticity in biological brains. While a number of training algorithms have been developed to date for spiking neural network (SNN) models of biological neuronal circuits, exiting methods rely on learning rules that adjust the synaptic strengths (or weights) directly, in order to obtain the desired network-level (or functional-level) performance. As such, they are not applicable to modifying plasticity in biological neuronal circuits, in which synaptic strengths only change as a result of pre- and post-synaptic neuron firings or biological mechanisms beyond our control. This paper presents a weight-free training algorithm that relies solely on adjusting the spatiotemporal delivery of neuron firings in order to optimize the network performance. The proposed weight-free algorithm does not require any knowledge of the SNN model or its plasticity mechanisms. As a result, this training approach is potentially realizable in vitro or in vivo via neural stimulation and recording technologies, such as optogenetics and multielectrode arrays, and could be utilized to control plasticity at multiple scales of biological neuronal circuits. The approach is demonstrated by training SNNs with hundreds of units to control a virtual insect navigating in an unknown environment.

Gelatin- hydroxyapatite- calcium sulphate based biomaterial for long term sustained delivery of bone morphogenic protein-2 and zoledronic acid for increased bone formation: In-vitro and in-vivo carrier properties

In this study, a novel macroporous composite biomaterial consisting of gelatin-hydroxyapatite-calcium sulphate for delivery of bone morphogenic protein-2 (rhBMP-2) and zoledronic acid (ZA) has been developed. The biomaterial scaffold has a porous structure and functionalization of the scaffold with rhBMP-2 induces osteogenic differentiation of MC3T3-e1 cells seen by a significant increase in biochemical and genetic markers of osteoblastic differentiation. In-vivo muscle pouch experiments showed higher mineralization using scaffold+rhBMP-2 when compared to an approved absorbable collagen sponge (ACS)+rhBMP-2 as verified by micro-CT. Co-delivery of rhBMP-2+ZA via the novel scaffold enabled a reduction in the effective rhBMP-2 doses. The presence of tartrate resistant acid phosphatase staining in the rhBMP-2 group indicates osteoclastic resorption, which could be stalled by adding ZA, which by speculation could explain the net increase in mineralization. The new scaffold allowed for slow release of rhBMP-2 in-vitro (3.3±0.1%) after 4weeks. Using single photon emission computed tomography (SPECT), the release kinetics of 125I–rhBMP-2 in-vivo was followed for 4weeks and a total of 65.3±15.2% 125I–rhBMP-2 was released from the scaffolds. In-vitro 14C–ZA release curve shows an initial burst release on day 1 (8.8±0.7%) followed by a slow release during the following 4weeks (13±0.1%). In-vivo, an initial release of 43.2±7.6% of 14C–ZA was detected after 1day, after which the scaffold retained the remaining ZA during 4-weeks. Taken together, our results show that the developed biomaterial is an efficient carrier for spatio-temporal delivery of rhBMP-2 and ZA leading to increased bone formation compared to commercially available carrier for rhBMP-2.

Dual non-viral gene delivery from microparticles within 3D high-density stem cell constructs for enhanced bone tissue engineering

High-density mesenchymal stem cell (MSC) aggregates can be guided to form bone-like tissue via endochondral ossification in vitro when culture media is supplemented with proteins, such as growth factors (GFs), to first guide the formation of a cartilage template, followed by culture with hypertrophic factors. Recent reports have recapitulated these results through the controlled spatiotemporal delivery of chondrogenic transforming growth factor-β1 (TGF-β1) and chondrogenic and osteogenic bone morphogenetic protein-2 (BMP-2) from microparticles embedded within human MSC aggregates to avoid diffusion limitations and the lengthy, costly in vitro culture necessary with repeat exogenous supplementation. However, since GFs have limited stability, localized gene delivery is a promising alternative to the use of proteins. Here, mineral-coated hydroxyapatite microparticles (MCM) capable of localized delivery of Lipofectamine-plasmid DNA (pDNA) nanocomplexes encoding for TGF-β1 (pTGF-β1) and BMP-2 (pBMP-2) were incorporated, alone or in combination, within MSC aggregates from three healthy porcine donors to induce sustained production of these transgenes. Three donor populations were investigated in this work due to the noted MSC donor-to-donor variability in differentiation capacity documented in the literature. Delivery of pBMP-2 within Donor 1 aggregates promoted chondrogenesis at week 2, followed by an enhanced osteogenic phenotype at week 4. Donor 2 and 3 aggregates did not promote robust glycosaminoglycan (GAG) production at week 2, but by week 4, Donor 2 aggregates with pTGF-β1/pBMP-2 and Donor 3 aggregates with both unloaded MCM and pBMP-2 enhanced osteogenesis compared to controls. These results demonstrate the ability to promote osteogenesis in stem cell aggregates through controlled, non-viral gene delivery within the cell masses. These findings also indicate the need to screen donor MSC regenerative potential in response to gene transfer prior to clinical application. Taken together, this work demonstrates a promising gene therapy approach to control stem cell fate in biomimetic 3D condensations for treatment of bone defects.

Blood derivatives awaken in regenerative medicine strategies to modulate wound healing.

Blood components play key roles in the modulation of the wound healing process and, together with the provisional fibrin matrix ability to selectively bind bioactive molecules and control its spatial-temporal presentation, define the complex microenvironment that characterize this biological process. As a biomimetic approach, the use of blood derivatives in regenerative strategies has awakened as a source of multiple therapeutic biomolecules. Nevertheless, and despite their clinical relevance, blood derivatives have been showing inconsistent therapeutic results due to several factors, including proper control over their delivery mechanisms. Herein, we highlight recent trends on the use biomaterials to protect, sequester and deliver these pools of biomolecules in tissue engineering and regenerative medicine approaches. Particular emphasis is given to strategies that enable to control their spatiotemporal delivery and improve the selectivity of presentation profiles of the biomolecules derived from blood derivatives rich in platelets. Finally, we discussed possible directions for biomaterials design to potentiate the aimed regenerative effects of blood derivatives and achieve efficient therapies.

Rapid initiation of guided bone regeneration driven by spatiotemporal delivery of IL-8 and BMP-2 from hierarchical MBG-based scaffold

Initiation of endogenous repair mechanisms, including key steps of stem cell recruitment and cartilage intermediate formation in endochondral ossification, is vital to regeneration of large bone defects. To biomimetically promote a rapid initiation and ensuing osteogenic stimulation, exogenous chemokine IL-8 and growth factor BMP-2 were orchestrated in a mesoporous bioactive glass (MBG)-based spatiotemporal delivery system, to achieve a rapid release of IL-8 followed by a long-term sustained release of BMP-2. The synergistic effect of IL-8 and BMP-2 on initiation stage of bone healing and underlying mechanism were thoroughly investigated in vitro and in vivo. Intriguingly, apart from its superiority in stem cell recruitment to BMP-2, IL-8 not only endowed a histological “prep-state” of endochondral ossification by up-regulating chondrogenic genes and inducing the formation of extensive cartilage tissues, facilitating rapid bone transformation by BMP-2, but also triggered a cellular “prep-state” with high expression of BMP receptors, enhancing the osteoinductivity of BMP-2. With the spatiotemporal delivery system, orchestrated signal stimuli of IL-8 and BMP-2 induced a rapid initiation including efficient stem cell recruitment and a “chondrogenic/osteogenic balance” at the first stage of endochondral ossification, and the scaffold facilitated sufficient osteoconductivity, together resulting in early extensive bone mineralization and an advanced regeneration throughout the repair of large bone defect. We believe this new idea could provide insights toward designing bone-repairing biomaterials with higher regenerative efficiency.

3D biomimetic artificial bone scaffolds with dual-cytokines spatiotemporal delivery for large weight-bearing bone defect repair

It is a great challenge to prepare “functional artificial bone” for the repair of large segmental defect, especially in weight-bearing bones. In this study, bioactive HA/PCL composite scaffolds that possess anatomical structure as autogenous bone were fabricated by CT-guided fused deposition modeling technique. The scaffolds can provide mechanical support and possess osteoconduction property. Then the VEGF-165/BMP-2 loaded hydrogel was filled into biomimetic artificial bone spatially to introduce osteoinduction and angioinduction ability via sustained release of these cytokines. It has been revealed that the cytokine-loaded hydrogel possessed good biodegradability and could release the VEGF-165/BMP-2 sustainedly and steadily. The synergistic effect of these two cytokines showed significant stimulation on the osteogenic gene expresssion of osteoblast in vitro and ectopic ossification in vivo. The scaffolds were then implanted into the rabbit tibial defect sites (1.2 cm) for bone regeneration for 12 weeks, indicating the best repair of defect in vivo, which was superior to the pure hydrogel/scaffolds or one-cytokine loaded hydrogel/scaffolds and close to autogenous bone graft. The strategy to construct an “anatomy-structure-function” trinity system as functional artificial bone shows great potential in replacing autogenous bone graft and applying in large bone defect repair clinically in future.

Advanced Growth Factor Delivery Systems in Wound Management and Skin Regeneration.

Growth factors are endogenous signaling molecules that regulate cellular responses required for wound healing processes such as migration, proliferation, and differentiation. However, exogenous application of growth factors has limited effectiveness in clinical settings due to their low in vivo stability, restricted absorption through skin around wound lesions, elimination by exudation prior to reaching the wound area, and other unwanted side effects. Sophisticated systems to control the spatio-temporal delivery of growth factors are required for the effective and safe use of growth factors as regenerative treatments in clinical practice, such as biomaterial-based drug delivery systems (DDSs). The current review describes the roles of growth factors in wound healing, their clinical applications for the treatment of chronic wounds, and advances in growth factor-loaded DDSs for enhanced wound healing, focusing on micro- and nano-particulate systems, scaffolds, hydrogels, and other miscellaneous systems.

Spatiotemporal delivery of nanoformulated liraglutide for cardiac regeneration after myocardial infarction.

The local, intramyocardial injection of proteins into the infarcted heart is an attractive option to initiate cardiac regeneration after myocardial infarction (MI). Liraglutide, which was developed as a treatment for type 2 diabetes, has been implicated as one of the most promising protein candidates in cardiac regeneration. A significant challenge to the therapeutic use of this protein is its short half-life in vivo. In this study, we evaluated the therapeutic effects and long-term retention of liraglutide loaded in poly(lactic-co-glycolic acid)–poly(ethylene glycol) (PLGA–PEG) nanoparticles (NP-liraglutide) on experimental MI. PLGA–PEG nanoparticles (NPs) have been shown to efficiently load liraglutide and release bioactive liraglutide in a sustained manner. For in vitro test, the released liraglutide retained bioactivity, as measured by its ability to activate liraglutide signaling pathways. Next, we compared the effects of an intramyocardial injection of saline, empty NPs, free liraglutide and NP-liraglutide in a rat model of MI. NPs were detected in the myocardium for up to 4 weeks. More importantly, an intramyocardial injection of NP-liraglutide was sufficient to improve cardiac function (P<0.05), attenuate the infarct size (P<0.05), preserve wall thickness (P<0.05), promote angiogenesis (P<0.05) and prevent cardiomyocyte apoptosis (P<0.05) at 4 weeks after injection without affecting glucose levels. The local, controlled, intramyocardial delivery of NP-liraglutide represents an effective and promising strategy for the treatment of MI.

Smart Nanostructures for Cargo Delivery: Uncaging and Activating by Light.

Nanotechnology has begun to play a remarkable role in various fields of science and technology. In biomedical applications, nanoparticles have opened new horizons, especially for biosensing, targeted delivery of therapeutics, and so forth. Among drug delivery systems (DDSs), smart nanocarriers that respond to specific stimuli in their environment represent a growing field. Nanoplatforms that can be activated by an external application of light can be used for a wide variety of photoactivated therapies, especially light-triggered DDSs, relying on photoisomerization, photo-cross-linking/un-cross-linking, photoreduction, and so forth. In addition, light activation has potential in photodynamic therapy, photothermal therapy, radiotherapy, protected delivery of bioactive moieties, anticancer drug delivery systems, and theranostics (i.e., real-time monitoring and tracking combined with a therapeutic action to different diseases sites and organs). Combinations of these approaches can lead to enhanced and synergistic therapies, employing light as a trigger or for activation. Nonlinear light absorption mechanisms such as two-photon absorption and photon upconversion have been employed in the design of light-responsive DDSs. The integration of a light stimulus into dual/multiresponsive nanocarriers can provide spatiotemporal controlled delivery and release of therapeutic agents, targeted and controlled nanosystems, combined delivery of two or more agents, their on-demand release under specific conditions, and so forth. Overall, light-activated nanomedicines and DDSs are expected to provide more effective therapies against serious diseases such as cancers, inflammation, infections, and cardiovascular disease with reduced side effects and will open new doors toward the treatment of patients worldwide.

Organic bioelectronics in medicine.

A major challenge in the growing field of bioelectronic medicine is the development of tissue interface technologies promoting device integration with biological tissues. Materials based on organic bioelectronics show great promise due to a unique combination of electronic and ionic conductivity properties. In this review, we outline exciting developments in the field of organic bioelectronics and demonstrate the medical importance of these active, electronically controllable materials. Importantly, organic bioelectronics offer a means to control cell-surface attachment as required for many device-tissue applications. Experiments have shown that cells readily attach and proliferate on reduced but not oxidized organic bioelectronic materials. In another application, the active properties of organic bioelectronics were used to develop electronically triggered systems for drug release. After incorporating drugs by advanced loading strategies, small compound drugs were released upon electrochemical trigger, independent of charge. Another type of delivery device was used to achieve well-controlled, spatiotemporal delivery of cationic drugs. Via electrophoretic transport within a polymer, cations were delivered with single-cell precision. Finally, organic bioelectronic materials are commonly used as electrode coatings improving the electrical properties of recording and stimulation electrodes. Because such coatings drastically reduce the electrode impedance, smaller electrodes with improved signal-to-noise ratio can be fabricated. Thus, rapid technological advancement combined with the creation of tiny electronic devices reacting to changes in the tissue environment helps to promote the transition from standard pharmaceutical therapy to treatment based on 'electroceuticals'. Moreover, the widening repertoire of organic bioelectronics will expand the options for true biological interfaces, providing the basis for personalized bioelectronic medicine.