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The supply of growth factors to engineered tissues is essential for many physiological processes. These processes include the proper organization of the cells into functioning tissues, maintenance of their viability, vasculogenesis, proliferation, and differentiation. Systems to efficiently control the release of growth factors were previously incorporated into tissue engineering scaffolds to affect cells. However, because the initial concentration of the factors in these systems is finite, their ability to provide a long-term physiological effect is limited. Here, we report on a new reloadable system in which 3D fibrous scaffolds conjugated with an anti His-tag antibody enable the retention and controlled release of any His-tag-modified proteinaceous growth factor. The scaffolds can be reloaded in vitro or in vivo with any His-tagged biomolecule at any time according to the physiological need. We show the ability of the scaffolds to release angiogenic factors in a static cell culture or under flow in a microfluidics device and effect on endothelial cells. We also demonstrate the potential of the system to be sequentially reloaded in vivo with various factors, and as a proof of concept, we provide evidence for the efficient in vivo vascularization of scaffolds after reloading with tagged VEGF.

Systemic fungal infections are an increasingly prevalent health problem, especially among immunocompromised patients. Antifungal drug development lags far behind in comparison to other types of antimicrobial drugs. Current commercially available antifungals are limited by their insufficient potency, side effects, drug-drug interactions, developing drug-resistance, and narrow formulation options. Here, we report the preparation and evaluation of two novel PEG amide conjugates of amphotericin B (AMB (1)): AB1 (4) and AM2 (5). These compounds are nonlabile, they are prepared in only two and three synthetic steps, respectively, and they show antifungal activity against a wide range of clinical fungal isolates. Their toxicity is significantly lower, and their water solubility is up to 5000-fold higher than that of AMB (1). In vivo efficacy studies in a mouse model of systemic candidiasis showed that AM2 (5) successfully cured all the mice at concentrations above 3.5 mg/kg body weight. In conclusion, these properties make AB1 (4) and AM2 (5) promising candidates for clinical use.

Seamless embedment of electronic devices in biological systems is expected to add the outstanding computing power, memory, and speed of electronics to the biochemical toolbox of nature. Such amalgamation requires transduction of electronic signals into biochemical cues that affect cells. Inspired by biology, where pathways are directed by molecular recognition, we propose and demonstrate a generic electrical-to-biological transducer comprising a two-state electronic antigen and a chimeric cell receptor engineered to bind the antigen exclusively in its "on" state. T-cells expressing these receptors remain inactivated with the antigen in its "off" state. Switching the antigen to its "on" state by an electrical signal leads to its recognition by the T-cells and correspondingly to cell activation.

Inspired by biology where pathways are triggered and suppressed by specific binding of two molecules, we realize a functional interface between electronics and biology by replacing one of the pair molecules with a two-state "electronic antigen" device comprising a hydroquinone monolayer assembled on gold, and choosing for the pair molecule an antibody that discriminates between the two electrically selected redox states of the monolayer. Application of an oxidative +0.6 V pulse to the antigen switches it to its benzoquinone state where antibodies bind the layer. A subsequent -0.6 V pulse reduces the monolayer back to the unbinding hydroquinone state, releases the specifically bound antibody molecules, and prevents further binding.

Seamless integration of biomolecules with manmade materials will most likely rely on molecular recognition and specific binding. In the following we show that combinatorial antibody libraries, based on the vast repertoire of the human immune system, can be harnessed to generate such binders. As a demonstration, we isolate antibody fragments that discriminate and bind selectively GaAs (111A) facets as opposed to GaAs (100). The isolated antibodies are utilized for exclusive localization of a fluorescent dye on (111A) surfaces in a structure comprising a mixture of (100) and (111A) surfaces. The potential importance of structure rigidity to facet recognition is suggested vis-a-vis published experiments with short and longer peptides.

B3(Fv)-PE38 is a recombinant single-chain immunotoxin in which the Fv region of monoclonal antibody B3 is connected to a truncated form of Pseudomonas exotoxin. It would be desirable to use the lysine residues of the molecule for chemical modification so that it can be derivatized with poly(ethylene glycol) to achieve reduced immunogenicity or with the Bolton-Hunter reagent for biodistribution studies. We found that derivatizing lysine residues of B3(Fv)-PE38 causes a marked loss of specific target cell cytotoxicity and/or immunoreactivity. Here we show that two lysine residues in the antibody-combining region of B3(Fv)-PE38 can be replaced with arginines, with only a small loss of cytotoxicity and no change in specificity. This mutant molecule is 3-fold more resistant to inactivation by derivatization with succinimidyl 4-(N-maleimidomethyl)cyclohexane 1-carboxylate (SMCC) or Bolton-Hunter reagent.