Tissue bioadhesives are widely used in dermatology, surgery rooms, and in the field. Despite their advantages over sutures and staples, currently available tissue glues are limited by their mechanical properties and toxicity. Here, a new approach is described for wound closure that is based on a biocompatible, low melting point four-armed N-hydroxy succinimide-modified polycaprolactone (star-PCL-NHS). Star-PCL-NHS is inserted into a hot melt glue gun, melts upon minimal pressure, and is extruded directly onto the wound, where it solidifies, bonding strongly with both edges of the wound. Changes in molecular weight allow control of adhesive strength, melting point, and elasticity properties. In vitro and in vivo evaluations confirm the biocompatibility of this system. The straightforward synthetic scheme and the simple delivery method, combined with the desirable mechanical properties, tunability, and tissue compatibility, are desirable traits in wound management.

The leading living bacteria formulations currently available are from a limited list of genera and are generally limited to gastrointestinal tract syndromes. A formulation composed of living Bacillus subtilis incorporated in a thermoresponsive hydrogel that hardens after administration on the skin and continuously produces antifungal agents is described. The ability of the formula to support bacteria growth and its mechanical properties and penetrability through the skin are fine-tuned by varying the ratio between polymer concentrations and bacterial media. The formula penetrates via the stratum corneum and accumulates in the epidermis without penetrating the inner, dermis layer. In vivo results mirror the results seen in vitro: bacillus formulations completely inhibit candida growth, demonstrating clinical effects comparable to those achieved by ketoconazole. LC-MS/MS analysis of the bacterial formulation confirms the presence of surfactin, the most powerful biosurfactant that possesses a broad antifungal activity. This platform may enable rational design of novel formulations composed of secreting bacteria inside a responsive, smart, hydrogel-which is the prerequisite for producing a successful drug delivery system.

Light responsive materials play an important role in many biomedical applications. Despite the great potential, commonly available systems are limited by their toxicity and lack of biodegradability. Here, an efficient light triggered system from safe, biodegradable star-poly(ethylene glycol) (star-PEG) and poly(ε-caprolactone) (PCL) with varying melting points controlled by the length of the CL segments is described. When incorporated with gold nanoshells (GNS) and exposed to near-infrared (NIR) irradiation, matrices temporarily disengage, thus allowing efficient on-demand healing and drug release. The responsiveness of this system to light, with its tailorable physical and healing properties, biocompatibility, biodegradability, and the capability to incorporate drugs and on-demand drug release are all desirable traits for numerous clinical applications.

Existing tissue adhesives have a trade-off between adhesive strength and biocompatibility. Here, we report a series of biocompatible multiarmed polycaprolactones (PCL) as tissue adhesives that can be released from a hot glue gun and the length of each arm was kept at ∼2–3 kg mol–1 in all the polymers. The adhesion properties were dependent on the number of functionalized (N-hydroxysuccinimide ester (NHS), aldehyde (CHO), and isocyanate (NCO)) arms of the multiarmed polymers. The more arms, the higher the adhesion strength. For example, the adhesion strength in binding cut rat skin increased from 2.3 N cm–2 for 2PCL-NHS to 11.2 N cm–2 for 8-PCL-NHS. CHO- and NCO-modified 8PCL also had suitable adhesive properties. All the multiarmed polymers had minimal cytotoxicity in vitro and good biocompatibility in vivo, suggesting their potential as promising alternative surgical adhesives.

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Surgical sealants are widely used to prevent seepage of fluids and liquids, promote hemostasis, and close incisions. Despite the remarkable progress the field of biomaterials has undergone, the clinical uses of surgical sealants are limited because of their short persistence time in vivo, toxicity, and high production costs. Here, the development of two complementary neat (solvent-free) prepolymers, PEG 4 -PLGA-NHS and PEG 4 -NH 2 , that harden upon mixing to yield an elastic biodegradable sealant is presented. The mechanical and rheological properties and cross-linking rate can be controlled by varying the ratio between the two prepolymers. The tested sealants show a longer persistence time compared with fibrin glue, minimal cytotoxicity in vitro, and excellent biocompatibility in vivo. The neat, multiarmed approach demonstrated here improves the mechanical and biocompatibility properties and provides a promising tissue sealant solution for wound closure in future surgical procedures.

COMMUNICATION (1 of 8)Nanoghosts (NGs) is a proprietary novel form of a targeted delivery platform, which is based on nanovesicles that are technologically reconstructed from the whole cytoplasmic membranes of human bone marrow-derived mesenchymal stem cells (MSCs). Initially developed for tumor-targeted drug Nanoghosts (NGs) are nanovesicles reconstructed from the cytoplasmic membranes of mesenchymal stem cells (MSCs). By retaining MSC membranes, the NGs retain the ability of these cells to home in on multiple tumors, laying the foundations, thereby, for the development of a targeted drug delivery platform. The susceptibility of MSCs to functional changes, following their exposure to cytokines or cancer-derived conditioned-media (CM), presents the opportunity to modify the NGs by conditioning their source cells. This opportunity is investigated by comparing the membrane protein composition and the tumor uptake of NGs derived from naïve MSCs (N-NG) against conditioned NGs made from MSCs pre-treated with conditionedmedia (CM-NG) or with a mix of the proinflammatory cytokines TNF-α and IL-1β (Cyto-NG). CM-NGs are found to be more targeted towards immune cells than Cyto-or N-NGs, while Cyto-NGs are the most tumor-targeted ones, with similar immune-targeting capacity as N-NGs but with a higher affinity towards endothelial cells. Proteomic variations were wider in the CM-NGs, with exceptionally higher levels of ICAM-1 compared to N-and Cyto-NGs. From a translational point of view, the data show that the tumor-targeting ability of the NGs, and possibly that of other MSC-derived extracellular vesicles, can be enhanced by simple conditioning of their source cells.

Particulate systems are widely used in biomedical applications, yet current systems are limited by their stability, complicated production processes, and the use of toxic excipients and cosolvents. Here, a new concept for an injectable nanocarrier system based on the in situ self‐assembled star polyethylene glycol (PEG)– poly(lactic‐co‐glycolic acid) (PLGA)/drug mixture is presented. The new injectable material is based on a neat (solvent‐free) liquid copolymer that self‐assembles after it is injected along with the drug to form a particulate delivery system. The nanocarriers’ formation rate and encapsulation capabilities of hydrophobic drugs can be fine‐tuned by changing the molecular weight of the PLGA segment. Furthermore, the starPEG–PLGA‐based system demonstrates potential as a drug carrier for hydrophobic drugs and shows biocompatibility with cell line culture.