Delicate Assembly of Ultrathin Hydroxyapatite Nanobelts with Nanoneedles Directed by Dissolved Cellulose.

Living organisms make use of a variety of inorganic and organic components to form biogenic minerals with hierarchical structures and fascinating properties, triggering the development of biomimetic mineralization. The introduction of organic additive is a versatile strategy, and a wide range of organics have already been adopted to mimic biosystems designing and synthesizing advanced functional minerals. Insoluble cellulose is the most abundant polysaccharide in nature, but the insolubility has limited its extensive applications. In this study, we first find that concentrated calcium chloride aqueous solution is an effective solvent for cellulose, and dissolved cellulose plays a pivotal role in directing the formation of ultrathin hydroxyapatite (HA) nanobelts of ca. 10 nm in thickness. To investigate the assembling process of the belt, samples collected at different reaction times were observed. The results indicate that nanoneedles form first, and then they assemble into the prototype of nanobelts by lateral/longitudinal aggregation and arrangement. Subsequently, the nanobelts gradually become dense, transparent, and smooth via crystallographic fusion of adjacent nanoneedles, indicating the highly elaborated evolution of morphology resulted from a time-dependent process. During the evolution of nanobelts, dissolved cellulose is supposed to participate in the mineralization of HA via the bonding of its hydrophilic groups with phosphate groups and calcium ions and the interaction of cellulose molecules with HA crystal planes. These findings provide unique insight into the application of dissolved cellulose in aqueous solution and an inspiration of a bottom-up strategy for designing delicate mineral assemblies directed by insoluble organics.

Single-component hyaluronic acid hydrogel adhesive based on phenylboronic ester bonds for hemostasis and wound closure.

Hydrogel tissue adhesives that currently available are often fabricated by mixing two or more polymeric components. Single-component hydrogels afford injectability, strong and reversible adhesion remain a formidable challenge. This research describes the creation of the first single-component hyaluronic acid hydrogel adhesive-based on phenylboronic acid-diol ester linkages. Phenylboronic acid can not only serve as a cross-linker to form hydrogel, but also act as an adhesion site for glycosyl compounds found in biological cell membranes. The rheological and compressive tests for the hydrogel show that it has excellent self-healing properties, good injectability and strong compressive strength. Adhesion tests demonstrated that the hydrogel has significantly greater adhesion strength than commercial fibrin glue. These findings suggest that the rational design of hydrogel precursors facilitates the formation of single-component networks and multiple functionalities. In vivo studies further proved the hydrogel was an ideal bio-adhesive with biocompatibility, absorbed wound exudate and hemostasis, and accelerated wound closure.

Injectable Adhesive Self-Healing Multicross-Linked Double-Network Hydrogel Facilitates Full-Thickness Skin Wound Healing.

The development of natural polymer-based hydrogels, combining outstanding injectability, self-healing, and tissue adhesion, with mechanical performance, able to facilitate full-thickness skin wound healing, remains challenging. We have developed an injectable micellar hydrogel (AF127/HA-ADH/OHA-Dop) with outstanding adhesive and self-healing properties able to accelerate full-thickness skin wound healing. Dopamine-functionalized oxidized hyaluronic acid (OHA-Dop), adipic acid dihydrazide-modified HA (HA-ADH), and aldehyde-terminated Pluronic F127 (AF127) were employed as polymer backbones. They were cross-linked in situ using Schiff base dynamic covalent bonds (AF127 micelle/HA-ADH network and HA-ADH/OHA-Dop network), hydrogen bonding, and π-π stacking interactions. The resulting multicross-linked double-network design forms a micellar hydrogel. The unique multicross-linked double-network structure endows the hydrogel with both improved injection abilities and mechanical performance while self-healing faster than single-network hydrogels. Inspired by mussel foot adhesive protein, OHA-Dop mimics the catechol groups seen in mussel proteins, endowing hydrogels with robust adhesion properties. We also demonstrate the potential of our hydrogels to accelerate full-thickness cutaneous wound closure and improve skin regeneration with reduced scarring. We anticipate that our hydrogel platform based on a novel multicross-linked double-network design will transform the future development of multifunctional wound dressings.

Solanesol derived therapeutic carriers for anticancer drug delivery.

Metabolites of a large number of inert drug carriers can cause long-term exogenous biological toxicity. Therefore, carriers with simultaneous therapeutic effects may be a good choice for drug delivery. Herein, a series of pharmacologically active solanesol derivatives were synthesized and investigated for use as micellar drug carriers for cancer therapy. Solanesyl thiosalicylic acid (STS) was first synthesized by introducing a thiosalicylic acid group to solanesol, inspired by the characteristic structure of farnesyl thiosalicylic acid (FTS) which is a non-toxic inhibitor of all active forms of the RAS protein. Then, two amphiphilic derivatives of STS were formed with ester- and hydrazone (HZ)-bond linked methyl poly(ethylene glycol)(mPEG), mPEG-STS and mPEG-HZ-STS, respectively. The PEGylated STS could be formed stable nano-sized micelles loaded with Doxorubicin (DOX). In vitro, DOX loaded mPEG-STS and mPEG-HZ-STS micelles exhibited stronger tumor inhibition ability compared with free DOX. In vivo, blank mPEG-STS and mPEG-HZ-STS micelles showed an obvious inhibiting effect on tumor growth while the drug loaded micelles had the greatest tumor inhibition effect. The enhanced therapeutic effects and the synergistic effect observed with this solanesol-based drug delivery system could be attributed to the inherent therapeutic qualities of the drug carriers.