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Multielectrode arrays would benefit from intimate engagement with neural cells, but typical arrays do not present a physical environment that mimics that of neural tissues. It is hypothesized that a porous, conductive hydrogel scaffold with appropriate mechanical and conductive properties could support neural cells in 3D, while tunable electrical and mechanical properties could modulate the growth and differentiation of the cellular networks. By incorporating carbon nanomaterials into an alginate hydrogel matrix, and then freeze‐drying the formulations, scaffolds which mimic neural tissue properties are formed. Neural progenitor cells (NPCs) incorporated in the scaffolds form neurite networks which span the material in 3D and differentiate into astrocytes and myelinating oligodendrocytes. Viscoelastic and more conductive scaffolds produce more dense neurite networks, with an increased percentage of astrocytes and higher myelination. Application of exogenous electrical stimulation to the scaffolds increases the percentage of astrocytes and the supporting cells localize differently with the surrounding neurons. The tunable biomaterial scaffolds can support neural cocultures for over 12 weeks, and enable a physiologically mimicking in vitro platform to study the formation of neuronal networks. As these materials have sufficient electrical properties to be used as electrodes in implantable arrays, they may allow for the creation of biohybrid neural interfaces and living electrodes.

Dermal wounds and their healing are a collection of complex, multistep processes which are poorly recapitulated by existing 2D in vitro platforms. Biomaterial scaffolds that support the 3D growth of cell cultures can better resemble the native dermal environment, while bioelectronics has been used as a tool to modulate cell proliferation, differentiation, and migration. A porous conductive hydrogel scaffold which mimics the properties of dermis, while promoting the viability and growth of fibroblasts is described. As these scaffolds are also electrically conductive, the application of exogenous electrical stimulation directs the migration of cells across and/or through the material. The mechanical properties of the scaffold, as well as the amplitude and/or duration of the electrical pulses, are independently tunable and further influence the resulting fibroblast networks. This biomaterial platform may enable better recapitulation of wound healing and can be utilized to develop and screen therapeutic interventions.

Stem cell‐derived kidney organoids contain nephron segments that recapitulate morphological and functional aspects of the human kidney. However, directed differentiation protocols for kidney organoids are largely conducted using biochemical signals to control differentiation. Here, the hypothesis that mechanical signals regulate nephrogenesis is investigated in 3D culture by encapsulating kidney organoids within viscoelastic alginate hydrogels with varying rates of stress relaxation. Tubular nephron segments are significantly more convoluted in kidney organoids differentiated in encapsulating hydrogels when compared with those in suspension culture. Hydrogel viscoelasticity regulates the spatial distribution of nephron segments within the differentiating kidney organoids. Consistent with these observations, a particle‐based computational model predicts that the extent of deformation of the hydrogel–organoid interface regulates the morphology of nephron segments. Elevated extracellular calcium levels in the culture medium, which can be impacted by the hydrogels, decrease the glomerulus‐to‐tubule ratio of nephron segments. These findings reveal that hydrogel encapsulation regulates nephron patterning and morphology and suggest that the mechanical microenvironment is an important design variable for kidney regenerative medicine.

Surface electrode arrays are mainly fabricated from rigid or elastic materials, and precisely manipulated ductile metal films, which offer limited stretchability. However, the living tissues to which they are applied are nonlinear viscoelastic materials, which can undergo significant mechanical deformation in dynamic biological environments. Further, the same arrays and compositions are often repurposed for vastly different tissues rather than optimizing the materials and mechanical properties of the implant for the target application. By first characterizing the desired biological environment, and then designing a technology for a particular organ, surface electrode arrays may be more conformable, and offer better interfaces to tissues while causing less damage. Here, the various materials used in each component of a surface electrode array are first reviewed, and then electrically active implants in three specific biological systems, the nervous system, the muscular system, and skin, are described. Finally, the fabrication of next‐generation surface arrays that overcome current limitations is discussed.

In emergency medicine, blood lactate levels are commonly measured to assess the severity and response to treatment of hypoperfusion‐related diseases (e.g., sepsis, trauma, cardiac arrest). Clinical blood lactate testing is conducted with laboratory analyzers, leading to a delay of 3 h between triage and lactate result. Here, a fluorescence‐based blood lactate assay, which can be utilized for bedside testing, based on measuring the hydrogen peroxide generated by the enzymatic oxidation of lactate is described. To establish a hydrogen peroxide assay, near‐infrared cyanine derivatives are screened and sulfo‐cyanine 7 is identified as a new horseradish peroxidase (HRP) substrate, which loses its fluorescence in presence of HRP and hydrogen peroxide. As hydrogen peroxide is rapidly cleared by erythrocytic catalase and glutathione peroxidase, sulfo‐cyanine 7, HRP, and lactate oxidase are encapsulated in a liposomal reaction compartment. In lactate‐spiked bovine whole blood, the newly developed lactate assay exhibits a linear response in a clinically relevant range after 10 min. Substituting lactate oxidase with glucose and alcohol oxidase allows for blood glucose, ethanol, and methanol biosensing, respectively. This easy‐to‐use, rapid, and versatile assay may be useful for the quantification of a variety of enzymatically oxidizable metabolites, drugs, and toxic substances in blood and potentially other biological fluids.

Neutrophils are essential effector cells for mediating rapid host defense and their insufficiency arising from therapy‐induced side‐effects, termed neutropenia, can lead to immunodeficiency‐associated complications. In autologous hematopoietic stem cell transplantation (HSCT), neutropenia is a complication that limits therapeutic efficacy. Here, we report the development and in vivo evaluation of an injectable, biodegradable hyaluronic acid (HA)‐based scaffold, termed HA cryogel, with myeloid responsive degradation behavior. In mouse models of immune deficiency, we show that the infiltration of functional myeloid‐lineage cells, specifically neutrophils, is essential to mediate HA cryogel degradation. Post‐HSCT neutropenia in recipient mice delayed degradation of HA cryogels by up to 3 weeks. We harnessed the neutrophil‐responsive degradation to sustain the release of granulocyte colony stimulating factor (G‐CSF) from HA cryogels. Sustained release of G‐CSF from HA cryogels enhanced post‐HSCT neutrophil recovery, comparable to pegylated G‐CSF, which, in turn, accelerated cryogel degradation. HA cryogels are a potential approach for enhancing neutrophils and concurrently assessing immune recovery in neutropenic hosts.

Traditional bolus vaccines often fail to sustain robust adaptive immune responses, typically requiring multiple booster shots for optimal efficacy. Additionally, these provide few opportunities to control the resulting subclasses of antibodies produced, which can mediate effector functions relevant to distinct disease settings. Here, it is found that three scaffold‐based vaccines, fabricated from poly(lactide‐co‐glycolide) (PLG), mesoporous silica rods, and alginate cryogels, induce robust, long‐term antibody responses to a model peptide antigen gonadotropin‐releasing hormone with single‐shot immunization. Compared to a bolus vaccine, PLG vaccines prolong germinal center formation and T follicular helper cell responses. Altering the presentation and release of the adjuvant (cytosine‐guanosine oligodeoxynucleotide, CpG) tunes the resulting IgG subclasses. Further, PLG vaccines elicit strong humoral responses against disease‐associated antigens HER2 peptide and pathogenicE. coli, protecting mice againstE. colichallenge more effectively than a bolus vaccine. Scaffold‐based vaccines may thus enable potent, durable and versatile humoral immune responses against disease.

Vaccines have shown significant promise in eliciting protective and therapeutic responses. However, most effective vaccines require several booster shots, and it is challenging to generate responses against synthetic molecules and peptides often used to increase target specificity and improve vaccine stability. As continuous antigen uptake and processing by antigen‐presenting cells and persistent toll‐like receptor priming can amplify humoral immunity, it is explored whether a single injection of a mesoporous silica micro‐rod (MSR) vaccine containing synthetic molecules and peptides can generate potent and durable humoral immunity. A single injection of the vaccine targeting a gonadotropin‐releasing hormone (GnRH) decapeptide elicits high anti‐GnRH titer for over 12 months and generated higher titers than bolus or alum formulations. Targeting a Her2/neu peptide within the Trastuzumab binding domain causes immunoreactivity to Her2 on tumor cells and, MSR vaccines against nicotine generated long‐term anti‐nicotine antibodies. A single MSR injection induced germinal center (GC) activity for more than 3 weeks, generated memory B cells, and 7 days of immunostimulation by the vaccine is required to generate effective antibody responses. The MSR vaccine represents a promising technology to bypass the need for multiple immunizations and enhance long‐term antibody production in the context of reproductive biology, cancer, and chronic addiction.