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Traumatic injury is a major cause of mortality, and poor wound healing affects millions of people. Thus, the development of effective wound dressings is essential for speeding up wound healing and decreasing mortality. In this study, a suspension of carboxylated brown algae cellulose nanofibers (BACNFs) with a high aspect ratio was freeze dried to prepare a sponge. The sponge showed high porosity and water absorption capacity; thus, it can absorb wound exudates when used as a wound dressing. In addition, quaternized β-chitin (QC) with antibacterial properties was intercalated into the interlayer space of the organic rectorite (OREC) viaelectrostatic interactions to obtain composite suspensions (QCRs) with improved antimicrobial activity compared to that of QC alone. Subsequently, the BACNF sponge was soaked in the QCR suspension to absorb QCRs viaelectrostatic interactions and hydrogen bonding from which cellulose nanofiber/quaternized chitin/organic rectorite composite (BACNF/QCR) sponges were constructed viafreeze-drying. The in vivoanimal tests demonstrated that the BACNF/QCR sponges rapidly induced hemostasis in a rat tail amputation test, making them superior to the traditional hemostatic materials. Furthermore, BACNFs/QCRs could substantially promote collagen synthesis and neovascularization, thereby accelerating wound healing 3 days earlier than gauze. This multi-functional biomedical material, fabricated using natural substances, shows great potential to be used for wound healing.

Hypoxia, acidosis and high level of glutathione (GSH) are characteristic abnormalities of the tumor microenvironment (TME), which promote tumor progression, metastasis, and resistance to therapies. Previous attempts to improve therapeutic efficacy were limited to modifying individual TME elements. In this study, we proposed a comprehensive TME modulation strategy that modifies multiple elements of the TME in order to enhance cisplatin anticancer efficacy. To do so, we prepared biocompatible lipid-coated CaO2/cisplatin nanoparticles (LipoCaO2/DDP) by the reverse microemulsion method. We imbued CaO2with the following reverse-TME properties: O2generation, increased pH value in tumor cells, and oxidation of intracellular glutathione. In vitroexperiments showed that LipoCaO2/DDP could deplete GSH for preventing the binding of GSH to cisplatin. Simultaneously, CaO2could significantly downregulate multidrug resistance-associated protein 2 (MRP2) by O2-dependent hypoxia-inducible factor 1 (HIF-1) inactivation. Hence, the complete drug-efflux pathway was blocked, and the anticancer effect of cisplatin was enhanced both in vitroand in vivo. Herein, we not only demonstrated the GSH depletion capacity of CaO2for the first time, but also provided a new comprehensive therapeutic strategy to overcome therapeutic resistance caused by multiple factors in the TME.

Successful bone healing depends significantly on the structure of blood clots and the functional responses of blood cells. Despite the importance of blood clots in osteogenesis, few studies have investigated the effects of blood clots during material-mediated bone regeneration. In this study, we implanted the bone graft substitute hydroxyapatite/tricalcium phosphate (HA/TCP) subcutaneously, with or without blood prefabrication, to evaluate the effects of blood clots on material-mediated bone formation. We observed that blood prefabricated HA/TCP induced ectopic vascularized bone-like structures, implying that blood prefabrication can induce a microenvironment sufficient for HA/TCP-mediated bone formation. The possible mechanisms were related to (1) modification of the fibrin network, which facilitates MSCs recruitment and differentiation, (2) modulation of the early osteoimmune environment with the upregulation of osteogenic factor BMP2, and (3) improved expression of VEGF and the enhancement of angiogenesis. These results demonstrate the multifaceted effects of blood clots in regulating osteogenesis, osteoclastogenesis, immune responses, and angiogenesis. Therefore, blood prefabrication can serve as a valuable strategy to improve the osteogenic capacity of materials, and prefabricating materials with blood clots prior to implantation should be encouraged. New generation bone substitute materials could target the modulation of a favorable blood clot response for improved bone regeneration.

Targeting tumor cell mitochondria is a prospective strategy for highly effective anticancer therapy. Consequently, the development of potent systems for the targeted delivery of mitochondria-acting therapeutics to mitochondria has the potential to boost this sector of nanomedicine. In this study, a functional mixed micellar system based on two co-assembled triblock copolymers, poly(2-(dimethylamino)ethyl methacrylate)-b-poly(-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) bearing triphenylphosphonium ligands (PDMAEMA(TPP+)20-b-PCL70-b-PDMAEMA(TPP+)20) and poly(ethylene oxide)-b-poly(-caprolactone)-b-poly(ethylene oxide) (PEO113-b-PCL70-b-PEO113), was assessed for the mitochondria targeted delivery of curcumin. The high proapoptotic activity of the system and the sub-cellular mechanisms of cytotoxicity were demonstrated using a chemosensitive HL-60 cell line and its resistant alternative HL-60/DOX. Next, the successful localization of nanocarriers in mitochondria was proved by fluorescence microscopy with the aid of DAPI (4′,6-diamidino-2-phenylindole) as a cellular localization tracker. The in vitroexperiments revealed the great potential of the functional system developed for the targeted delivery of curcumin to mitochondria, causing programmed tumor cell death.

The structure of DNA is susceptible to alterations at high temperature and on changing pH, irradiation and exposure to DNase. Options to protect and preserve DNA during storage are important for applications in genetic diagnosis, identity authentication, drug development and bioresearch. In the present study, the stability of total DNA purified from human dermal fibroblast cells, as well as that of plasmid DNA, was studied in silk protein materials. The DNA/silk mixtures were stabilized on filter paper (silk/DNA + filter) or filter paper pre-coated with silk and treated with methanol (silk/DNA + PT-filter) as a route to practical utility. After air-drying and water extraction, 50–70% of the DNA and silk could be retrieved and showed a single band on electrophoretic gels. 6% silk/DNA + PT-filter samples provided improved stability in comparison with 3% silk/DNA + filter samples and DNA + filter samples for DNA preservation, with ∼40% of the band intensity remaining at 37 °C after 40 days and ∼10% after exposure to UV light for 10 hours. Quantitative analysis using the PicoGreen assay confirmed the results. The use of Tris/borate/EDTA (TBE) buffer enhanced the preservation and/or extraction of the DNA. The DNA extracted after storage maintained integrity and function based on serving as a functional template for PCR amplification of the gene for zinc finger protein 750 (ZNF750) and for transgene expression of red fluorescence protein (dsRed) in HEK293 cells. The high molecular weight and high content of a crystalline beta-sheet structure formed on the coated surfaces likely accounted for the preservation effects observed for the silk/DNA + PT-filter samples. Although similar preservation effects were also obtained for lyophilized silk/DNA samples, the rapid and simple processing available with the silk–DNA–filter membrane system makes it appealing for future applications.

Stimuli-responsive hydrogels, known as smart hydrogels, are three-dimensional amphiphilic or hydrophilic polymer networks that are able to change their volume or phase, and other properties, including viscosity, structure, and dimension, in response to changes in pH, temperature, and magnetic or electric field. Highly swellable, dual-responsive bovine serum albumin (BSA)-based injectable hydrogels are prepared here by the chemical conjugation of pH- and temperature-responsive oligo(sulfamethazine acrylate-co-N-isopropylacrylamide) (oligo(SMA-co-NIPAM)) copolymers on the surface of BSA through carbodiimide-mediated chemistry. The pH- and temperature-responsive oligomer-bearing BSA conjugates show rapid sol-to-gel phase transition properties. Specifically, the free-flowing conjugates at high pH (pH 8.4, 23 °C) are transformed to a viscoelastic gel under physiological conditions (pH 7.4, 37 °C). The swelling ratio, gel strength, and pore size of the BSA hydrogel were tuned by altering the conjugation ratio of the oligo(SMA-co-NIPAM) copolymers of various lengths and compositions to BSA. Subcutaneously administered BSA conjugate sols into the dorsal region of Sprague-Dawley rats formed an in situgel. When the oligo(NIPAM) content in the hydrogel was high, the degradation rate of BSA hydrogels was remarkably slow, and two weeks after in vivoadministration, the hydrogels with high oligo(NIPAM) had swollen more than 4-fold. An in vivobiodegradation study demonstrated that no necrosis or hemorrhage was observed in the tissues with the hydrogels. The concurrent stimuli-responsivity under physiological conditions and high elasticity suggest that these smart hydrogels may open a new avenue for hydrogel applications.

In this work, new copolymers containing either MMA and 18C6 crown-ether pendants, or PEG, MMA and 18C6 crown-ether pendants were synthesized to test the idea that sequestering structural alkali-earth ions from the bacterial outer membrane (OM) may lead to bacterial death. The copolymers were obtained either viauncontrolled radical polymerization or ATRP; the latter approached allowed us to produce not only linear copolymers but also branched Y-like structures. After checking for the capability of complexing magnesium and calcium ions, the antimicrobial activity of all copolymers was tested placing their casted plaques in contact with pure water E. colisuspensions. All plaques adsorbed alkali-earth ions and killed bacteria, albeit with different antimicrobial efficiencies. Differences in the latter characteristic were attributed to different plaque roughness. The role of the 18C6 crown-ether pendants was elucidated by pre-saturating plaques with Mg/Ca ions, the marked reduction in antimicrobial efficiency indicating that losing the latter from OM due to surface complexation does play an important role in killing bacteria at short (<5 h) contact times. At longer times, the mode of action is instead related to the poly-cationic nature acquired by the plaques due to ion sequestering.

Cyclodextrins (CDs) represent the most extensively investigated cyclic molecules due to their wide availability, facile functionalization, unique amphiphilicity and inclusion capacity. The marriage of CD chemistry with polymer science has generated novel biomaterials by integrating supermolecular host–guest chemistry and state-of-the-art polymer chemistry techniques. The current mini-review focuses on the recent progress in CD-functionalized polymers as drug carriers for cancer therapy. CD-functionalized polymers with different structures are summarized. Their application as drug carriers for cancer therapy is then highlighted. In the end, the future directions of this rapidly developing research field are discussed.

Thermosensitive liposomes are a promising approach to controlled release and reduced drug cytotoxicity. Low molecular weight N-isopropylacrylamide (NIPAm) oligomers (NOs) with different architectures (main chain NOs (MCNOs) and side chain NOs (SCNOs)) were synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization and radical polymerization and then separately used to prepare thermosensitive liposomes. A more controlled and enhanced release was observed for both NO liposomes compared to pristine ones. Two release mechanisms depending on the oligomer architecture, namely “nail” for MCNOs and “comb” for SCNOs, are proposed. In addition to thermosensitivity, the cancer targeting property of NO liposomes was achieved by further biotinylation of the delivery system.

The incorporation of small bioactive peptide motifs within robust hydrogels constitutes a facile procedure to chemically functionalise cell and tissue scaffolds. In this study, a novel approach to utilise Fmoc-linked peptide amphiphiles comprising the bio-functional cell-adhesion RGDS motif within biomimetic collagen gels was developed. The composite scaffolds thus created were shown to maintain the mechanical properties of the collagen gel while presenting additional bio-activity. In particular, these materials enhanced the adhesion and proliferation of viable human corneal stromal fibroblasts by 300% compared to non-functionalised gels. Furthermore, the incorporation of Fmoc-RGDS nanostructures within the collagen matrix significantly suppressed gel shrinkage resulting from the contractile action of encapsulated fibroblasts once activated by serum proteins. These mechanical and biological properties demonstrate that the incorporation of peptide amphiphiles provides a suitable and easy method to circumvent specific biomaterial limitations, such as cell-derived shrinkage, for improved performance in tissue engineering and regenerative medicine applications.