Smart drug carrier with function-oriented adaptations is highly desired due to its unique properties in medical applications. Herein, adaptive chitosan hollow microspheres (CHM) are fabricated by employing interfacial Schiff-base bonding reaction. Hydrophilic macromolecules of glycol chitosan are fixed at the oil/water interface through numerous hydrophobic small molecules of borneol 4-formylbenzoate, forming the CHM with a positively charged surface and lipophilic cavity. These CHM have an average size of 400–1000 nm after passing through the 0.22 μm apertures of filter paper. This phenomenon combined with SEM measurements demonstrates its remarkable shape-adaptive behavior. Furthermore, the CHM present a pH-dependence of structural stability. When pH value reduces from 7.06 to 5.01, the CHM begin to lose their integrity. All those characteristics make the CHM an intelligent drug carrier, especially for water-insoluble anticancer drugs, paclitaxel (PTX) in particular. Both cell uptake and cell cytotoxicity assays suggest that the PTX-loaded CHM are highly efficient on HepG2 and A549 cells. Therefore, rather than most of the traditional materials, these adaptive CHM show great potential as a novel drug carrier.

Montmorillonite (MMT) is considered to be the most effective hemostat among natural phyllosilicates. However, there is a barrier against using MMT for the commercial hemostatics because the invaded MMT powders might cause thrombosis in vessel. Until now, it is still a challenge to manage the release of MMT and eliminate its side effect. Herein, we present a graphene-MMT composite sponge (GMCS), synthesized under a hydrothermal reaction, fixing MMT powders into the cross-linked graphene sheets. We demonstrate that only a few embedded MMT can evoke remarkable platelet stimulation at the sponge interface, while maintaining fast plasma absorbency of the innate sponge. In the synergy of the above hemostatic mechanisms, the GMCS can rapidly stop bleeding in approximately 85 s in rabbit artery injury test. More importantly, computed tomography angiography certifies that the GMCS does not cause thrombus or blood clot in vessels. Cytotoxicity assay further highlights its biocompatibility. In-depth analysis proposes that two-dimensional graphene overmatches one-dimensional linear polymers in the composite construction, and dimension transformation of blood distribution plays a crucial role for reinforcing the hemostatic performance. This GMCS hemostat not only opens a new perspective for graphene composite, but also makes a new chance of using clays for trauma therapy.Keywords: composite; graphene; hemostasis; hemostatic sponge; montmorillonite;

•Modulus regulated 3D-Cell proliferation is studied in a self-healing hydrogel.•This self-healing hydrogel is growth-factor-free, modulus tunable and injectable.•3D cell proliferation before and after injection is presented.•The proliferating rates of the encapsulated cells are quantified.•This hydrogel offer potentially higher therapeutic efficiency for cell-therapy.Cell therapy has attracted wide attention among researchers in biomaterial and medical areas. As a carrier, hydrogels that could keep high viability of the embedded cells have been developed. However, few researches were conducted on 3D cell proliferation, a key factor for cell therapy, especially after injection. In this study, we demonstrated for the first time the proliferation regulation of the 3D-embedded L929 cells in a modulus-tunable and injectable self-healing hydrogel before and after injection without adding specific growth factor. The cells showed a stiffness-dependent proliferation to grow faster in higher stiffness hydrogels. The proliferating rates of the encapsulated cells before and after injection were quantified, and the shearing force as a possible negative influence factor was discussed, suggesting the both internal property of the hydrogel and injection process are critical for further practical applications. Due to the high operability and good biocompatibility, this injectable self-healing hydrogel can be a promising carrier for cell therapy.Proliferation of the 3D-embedded cells was studied using a modulus-tunable self-healing hydrogel carrier, especially after injection.

Chemotherapy has contributed greatly in clinical anti-tumor treatment. However, the traditional method of drug delivery by intravenous injection has several drawbacks, such as low delivery efficiency, high toxicity and frequent pain caused by injection. To overcome these defects, intra-tumor injection has been proposed in recent years, and the development of suitable carriers to locate the drug at the desired position for optimum dispersal is crucial to realize the superiority of intra-tumor injection. Herein, we report the application of a chitosan-based self-healing hydrogel, constructed through Schiff's bases, as an injectable drug carrier for in vivo intra-tumor therapy. This smart carrier could deliver highly concentrated anti-tumor drug (Taxol) to the desired position (human hepatocarcinoma tumor) for steady in situ release at a safe level. The self-healing drug carrier could adapt to the intra-tumor structure and regenerate as a whole, thus avoiding the fast leak of loaded drug, leading to admirable therapeutic effects compared with controls (direct injection of drug solution or use of non-self-healable thermal-sensitive hydrogel as the drug carrier). Due to its excellent biocompatibility and high operability, this injectable self-healing hydrogel might be a promising drug carrier for tumor chemotherapy and other medical applications.

By using an easily available PEG derivative and biopolymer chitosan, a self-healing hydrogel has been facilely prepared through the dynamic Schiff base. This biocompatible self-healing hydrogel can be used for drug-delivery, 3D cell culture and as a basic platform to develop some organic-inorganic biohybrids. This mini-review summarized recent research about that chitosan based self-healing hydrogel and related materials, and discussed some future bio-applications of that hydrogelDownload high-res image (179KB)Download full-size imageA chitosan-based biocompatible self-healing hydrogel has been facilely prepared and used for bioapplications.

•Graphene oxide-borneol (GOB) composite is a novel antifungal material.•GOB against adhesion and growth of M. racemosus on its surface for a long-term.•Carbon stereochemistry plays a crucial role on antifungal properties rather than hydrophobicity.•GOB is biocompatible material.•Landing experiment and sensing mechanism are proposed in this work.Although antibacterial activities of graphene oxide (GO) and its derivatives have been investigated comprehensively, their antifungal properties are still less reported. Yet, fungal contamination seriously threatens the public health. Herein, we present a design of graphene oxide-borneol (GOB) composite, and report its great antifungal effect. This GOB composite is prepared by esterification of borneol with thiomalic-acid-modified GO sheets, where the linker molecule is used to increase surface carboxyl groups. As a result, the antifungal activity displays a dramatically conversion from no activity of GO and its derivatives to distinct antifungal adhesion and growth inhibition of the GOB. Under microscopy, few spores can be found on the GOB surface, while large numbers of sporangia and spores adhere and grow on the control groups. It is also worth noting that on the GOB sample the fallen spore does not germinate even after 5 days, demonstrating a long-term antifungal effect of the GOB composite. Further studies confirm that carbon stereochemistry rather than wettability plays a crucial role on the antifungal adhesion properties. This study not only highlights a promising GOB composite as a candidate of graphene-based antifungal agent, but also provides us with in-depth understanding of the interactions between fungi and graphene-based materials.Download high-res image (212KB)Download full-size image

2,3-Diaminopropionic acid (DapA), a medicinal amino acid, is used for the first time to prepare a DapA cross-linked graphene sponge (DCGS) for hemostasis treatment. In a comparison with the reported ethanediamine (EDA) cross-linked graphene sponge (CGS), this carboxyl-functionalized DCGS can not only quickly absorb plasma, but also stimulate erythrocytes and platelets to change their normal form and structure at the interface, which largely affects a cell’s metabolism and biofunction, thus further promoting blood coagulation. Whole blood clotting and rat-tail amputation tests indicated that on the basis of the additional interfacial stimulation, the hemostatic efficiency of the DCGS has been significantly improved in comparison with that of the CGS control (P < 0.05). In-depth insight revealed that the increased oxidation degree and the negative charge density play the crucial rule in the enhanced hemostatic performance. The chiral effect contributes mainly to the selective adhesion of erythrocytes and platelets rather than practical hemostasis. Nevertheless, this presentation demonstrated that, on the premise of keeping the fast absorbability, this is an effective method to improve the hemostatic efficiency by enhancing the cell/graphene interface interaction.Keywords: 2,3-diaminopropionic acid; carboxyl-functionalization; cross-linked graphene sponge; hemostasis; interfacial stimulation

On the basis of the use of photopolymerization technology, a facile and reliable method for in situ preparation of silver nanoparticles (AgNPs) within PNIPAAm functional surfaces is presented as a means to achieve nonfouling, antibacterial films. The surface properties were characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), water contact angle, and thermogravimetric analysis (TGA). The antibacterial and release properties of the surfaces were tested against E. coli: at 37 °C (above the LCST of PNIPAAm), the functional films facilitated the attachment of bacteria, which were then killed by the AgNPs. Changing temperature to 4 °C (below the LCST), swollen PNIPAAm chains led the release of dead bacteria. The results showed that AgNPs/PNIPAAm hybrid surfaces offer a “smart” antibacterial capability in response to the change of environmental temperature.Keywords: antimicrobial; photopolymerization; poly(N-isopropylacrylamide); silver nanoparticles; Surface modification

Poly(methyl methacrylate) (PMMA) is a widely used biomaterial. But there is still a challenge facing its unwanted bacterial adhesion because the subsequent biofilm formation usually leads to failure of related implants. Herein, we present a borneol-modified PMMA based on a facile and effective stereochemical strategy, generating antibacterial copolymer named as P(MMA-co-BA). It was synthesized by free radical polymerization and studied with different ratio between methyl methacrylate (MMA) and borneol acrylate (BA) monomers. NMR, GPC, and EA, etc., were used to confirm their chemical features. Their films were challenged with Escherichia coli (Gram-negative) and Bacillus subtilis (Gram-positive), showing a BA content dependent antibacterial performance. The minimum effective dose should be 10%. Then in vivo subcutaneous implantations in mice demonstrated their biocompatibilities through routine histotomy and HE staining. Therefore, P(MMA-co-BA)s not only exhibited their unique antibacterial character but also suggested a potential for the safe usage of borneol-modified PMMA frame and devices for further implantation.Keywords: antibacterial adhesion; borneol; copolymer; implant; poly(methyl methacrylate)

Cellulose fibers modified to obtain antifungal activity have attracted much attention due to their versatile applications, although there are still some problems associated with the conventional protocols, including the toxicity to organisms, unwanted resistance, and gradually increasing environmental pressure. A natural and safe strategy is desired to design new types of antifungal cellulose. Herein, we present a borneol-grafted cellulose (BGC) by covalently tethering L-borneol, a natural product, to cellulose. The attained BGC has been characterized to confirm the chemical and amorphous features using a combination of spectroscopic and analytical techniques. This BGC material was subsequently challenged with Mucor racemosus and Aspergillus niger, and exhibited a remarkable performance in antifungal adhesion and fungal growth inhibition, suggesting the grafted borneol moieties are crucial for influencing the tactile sensing of fungal cells and subsequent selective inadhesion. The BGC has also been evaluated as a non-cytotoxic material, implying its great potential for biomedical and sanitary applications.

A novel multiple responsive polymer-peptide bioconjugate, which exhibits responses to calcium ion, pH, and temperature, was presented. In our study, a peptide with calcium ion response was conjugated with a thermo-responsive polymer at the N terminus to generate a polymer-peptide bioconjugate. Several experiments were conducted to characterize the environmental response of the bioconjugate. Results suggest that electrostatic interaction and hydrogen bonding are the driving forces for peptide self-assembly. Additionally, the incorporation of polymer endows new property to the peptide, though it may disrupt the inner-molecular interactions between peptides in some extent. This study will highlight the fundamental understanding of polymer-peptides that are of potential utility as stimuli-responsive biomaterials.

•Cross-linked graphene sponge (CGS) shows remarkable hemostatic performance (2–4 min).•Fast blood coagulation is attributed to the enrichment of hemocytes and platelets.•The CGS accelerates clotting within 60 s, faster than natural coagulating of blood.•The CGS is low cost, ultra-light, portable, long shelf life and nontoxicity.•The facile prepared CGS offers a new platform for treating trauma bleeding.In this study, we demonstrate for the first time the remarkable hemostatic performance of a cross-linked graphene sponge (CGS) as a superb hemostat. The CGS can absorb plasma immediately (<40 ms) to form a blood cell layer and promotes subsequent clotting. The interaction between the interface of the CGS and blood cells reveals that the fast blood coagulation is primarily attributed to the enrichment of hemocytes and platelets on the wound surface. An in vitro dynamic whole-blood clotting test further highlights the effectiveness of the CGS. Considering the facile preparation, low cost, nontoxicity, and long shelf life of the portable black sponge, the CGS has great potential for trauma treatment.

During its adhesion on external surfaces, a cell exhibits obvious inclination to different molecular chirality, which encourages us to develop a new type of antibacterial material catering to the “chiral taste” of bacteria. On the basis of the natural product borneol (a camphane-type bicyclic monoterpene), a series of borneol-based polymer, polyborneolacrylate (PBA), was successfully prepared and showed superior antibacterial adhesion properties resulting from the borneol isomers on material surface. The results of this study reveal that bacteria simply dislike this type of stubborn surface of PBA, and the PBA surface stereochemistry contributes to the interfacial antibacterial activities. The PBA polymers were evaluated as noncytotoxic and can be simply synthesized, demonstrating their great potential for biomedical applications.Keywords: antibacterial adhesion; biomaterial; borneol; chirality; polymer; stereochemistry