The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.

In recent years, cardiac patches have been developed for the treatment of myocardial infarction. However, the fixation approaches onto the tissue through suture or phototriggered reaction inevitably cause new tissue damage. Herein, a paintable hydrogel is constructed based on Fe -triggered simultaneous polymerization of covalently linked pyrrole and dopamine in the hyperbranched chains where the in situ formed conductive polypyrrole also uniquely serves to crosslink network. This conductive and adhesive hydrogel can be conveniently painted as a patch onto the heart surface without adverse liquid leakage. The functional patch whose conductivity is equivalent to that of normal myocardium is strongly bonded to the beating heart within 4 weeks, accordingly efficiently boosting the transmission of electrophysiological signals. Eventually, the reconstruction of cardiac function and revascularization of the infarct myocardium are remarkably improved. The translatable suture-free strategy reported in this work is promising to address the human clinical challenges in cardiac tissue engineering.

is greatly decreased or even eliminated. For instance, the widely used cyanoacrylate adhesives exhibit strong adhesion in air, but when applied in water environment, they are hardened quickly to form a layer of stiff plastics, eventually resulting in the loss of adhesion. [9] The commercially available epoxy resins [10] and polyurethanes [11] are reported to demonstrate strong underwater adhesion, but long time of curing is usually required. Recently, host-guest chemistry strategy was reportedly employed to prepare underwater adhesives; however, the substrate surface needs to be modified in advance. [5,12] In addition, electrostatic and hydrophobic interactions were also proved to contribute to enhanced underwater adhesion, but the adhesion strength was relatively poor. [13,14] In nature, many organisms, such as mussels, barnacles, and castle worms, have evolved an unparalleled mechanism to perfectly tackle the underwater adhesion problem. [15][16][17] The finding of universality of catechol chemistry for wet adhesion has provided a valuable biomimetic source to develop diverse adhesives for use in aqueous environments. However, several problems, such as the complexity of administration, release of harmful organic solvents, [18,19] long-term curing, [2] need for oxidant addition, [20,21] and low adhesion strength, [18,22] may hamper the actual applications of these bioinspired adhesives. Although numerous dopamine-based adhesives have been reported and shown to bond various material surfaces, strong adhesion in water and particularly blood environment, remains nonexistent so far.Increasing studies on bioadhesives secreted by molluscs and insects have suggested that liquid coacervation plays a critical role in achieving underwater adhesion. [13] In this process, phase separation and concurrently increased hydrophobicity induced by coacervation can dispel the hydrated water on the interface, leading to much enhanced interaction of adhesive groups with the adherent and thus stable underwater adhesion. Up to date, several complex coacervate adhesives with linear structure have been reported, but the occurrence of those coacervations in water needs external triggers, such as temperature, [13] pH, [20,23] and iron strength. [24] Compared to linear counterparts, hyperbranched polymer (HBP) has a unique highly branched Despite recent advance in bioinspired adhesives, achieving strong adhesion and sealing hemostasis in aqueous and blood environments is challenging. A hyperbranched polymer (HBP) with a hydrophobic backbone and hydrophilic adhesive catechol side branches is designed and synthesized based on Michael addition reaction of multi-vinyl monomers with dopamine.It is demonstrated that upon contacting water, the hydrophobic chains selfaggregate to form coacervates quickly, displacing water molecules on the adherent surface to trigger increased exposure of catechol groups and thus rapidly strong adhesion to diverse materials from low surface energy to high energy in various environments, such as deionized water, sea ...

The emerging 3D printing technique allows for tailoring hydrogel‐based soft structure tissue scaffolds for individualized therapy of osteochondral defects. However, the weak mechanical strength and uncontrollable swelling intrinsic to conventional hydrogels restrain their use as bioinks. Here, a high‐strength thermoresponsive supramolecular copolymer hydrogel is synthesized by one‐step copolymerization of dual hydrogen bonding monomers, N‐acryloyl glycinamide, and N‐[tris(hydroxymethyl)methyl] acrylamide. The obtained copolymer hydrogels demonstrate excellent mechanical properties—robust tensile strength (up to 0.41 MPa), large stretchability (up to 860%), and high compressive strength (up to 8.4 MPa). The rapid thermoreversible gel ⇔ sol transition behavior makes this copolymer hydrogel suitable for direct 3D printing. Successful preparation of 3D‐printed biohybrid gradient hydrogel scaffolds is demonstrated with controllable 3D architecture, owing to shear thinning property which allows continuous extrusion through a needle and also immediate gelation of fluid upon deposition on the cooled substrate. Furthermore, this biohybrid gradient hydrogel scaffold printed with transforming growth factor beta 1 and β‐tricalciumphosphate on distinct layers facilitates the attachment, spreading, and chondrogenic and osteogenic differentiation of human bone marrow stem cells (hBMSCs) in vitro. The in vivo experiments reveal that the 3D‐printed biohybrid gradient hydrogel scaffolds significantly accelerate simultaneous regeneration of cartilage and subchondral bone in a rat model.

Biomacromolecules with poor mechanical properties cannot satisfy the stringent requirement for load‐bearing as bioscaffolds. Herein, a biodegradable high‐strength supramolecular polymer strengthened hydrogel composed of cleavable poly( N ‐acryloyl 2‐glycine) (PACG) and methacrylated gelatin (GelMA) (PACG‐GelMA) is successfully constructed by photo‐initiated polymerization. Introducing hydrogen bond‐strengthened PACG contributes to a significant increase in the mechanical strengths of gelatin hydrogel with a high tensile strength (up to 1.1 MPa), outstanding compressive strength (up to 12.4 MPa), large Young's modulus (up to 320 kPa), and high compression modulus (up to 837 kPa). In turn, the GelMA chemical crosslinking could stabilize the temporary PACG network, showing tunable biodegradability by adjusting ACG/GelMA ratios. Further, a biohybrid gradient scaffold consisting of top layer of PACG‐GelMA hydrogel‐Mn 2+ and bottom layer of PACG‐GelMA hydrogel‐bioactive glass is fabricated for repair of osteochondral defects by a 3D printing technique. In vitro biological experiments demonstrate that the biohybrid gradient hydrogel scaffold not only supports cell attachment and spreading but also enhances gene expression of chondrogenic‐related and osteogenic‐related differentiation of human bone marrow stem cells. Around 12 weeks after in vivo implantation, the biohybrid gradient hydrogel scaffold significantly facilitates concurrent regeneration of cartilage and subchondral bone in a rat model.