MPC-n (IgG) improves long-term cognitive impairment in the mouse model of repetitive mild traumatic brain injury.

BACKGROUND: Contact sports athletes and military personnel who suffered a repetitive mild traumatic brain injury (rmTBI) are at high risk of neurodegenerative diseases such as advanced dementia and chronic traumatic encephalopathy (CTE). However, due to the lack of specific biological indicators in clinical practice, the diagnosis and treatment of rmTBI are quite limited. METHODS: We used 2-methacryloyloxyethyl phosphorylcholine (MPC)-nanocapsules to deliver immunoglobulins (IgG), which can increase the delivery efficiency and specific target of IgG while reducing the effective therapeutic dose of the drug. RESULTS: Our results demonstrated that MPC-capsuled immunoglobulins (MPC-n (IgG)) significantly alleviated cognitive impairment, hippocampal atrophy, p-Tau deposition, and myelin injury in rmTBI mice compared with free IgG. Furthermore, MPC-n (IgG) can also effectively inhibit the activation of microglia and the release of inflammatory factors. CONCLUSIONS: In the present study, we put forward an efficient strategy for the treatment of rmTBI-related cognitive impairment and provide evidence for the administration of low-dose IgG.

Viscous, Hofmeister Effect-Enhanced Macromolecular Adhesives for Effective Bonding in Seawater.

Deployment of adhesives in natural seawater to in situ bonds is urgently needed in engineering fields. However, stable adhesion in natural seawater remains a challenge due to the turbulent environment and high ion concentration. Herein, we reported a viscous, macromolecular underwater adhesive enhanced by Hofmeister effect (EHUA) for practical application in dynamic seawater. EHUA was synthesized via a facile one-step copolymerization. After transferred into seawater, the solvent of EHUA was exchanged to seawater, and thereby hydrogen bonds inside the adhesive were activated and enhanced by Hofmeister effect. We demonstrated EHUA can adhere on the surface in turbulent seawater, and the adhesive strength could reach 1.691 MPa. In addition, the adhesives also exhibited long-term storage stability and convenient recyclability. These fascinating properties enable adhesives to seal leaky pipelines, repair damaged ships and construct buildings in turbulent seawater. This work may open an avenue for the design of adhesives for seawater environments.

"Sustained irrigation" effect enhanced the accumulation and retention of ultra-long circulating nanoparticles in tumor.

The development of ultra-long circulating nanodrug delivery systems have showed distinct advantage in maintaining the long-lasting tumor retention. Although the relationship between extended tumor retention and ultra-long plasma half-life was apparent, there was still a lack of experimental evidence to reveal the enhancement mechanism. Herein, we proposed a concept of "Sustained Irrigation" effect ("SI" effect) to elucidate that it was through sustained blood irrigation that the ultra-long circulating nanoparticles achieved long-lasting tumor retention. Besides, in order to intuitively verify the "SI" effect, we developed an "ON-OFF-ON" fluorescence switch technology. The ultra-long circulating delivery nanoparticle was constructed by encapsulating the protein with hydrophilic polymer shell. Nanoparticles with ultra-long plasma half-life (t1/2>40 h) fabricated by this method were employed as models for demonstrating the "SI" effect. The recovery of Cy5.5 fluorescence after the laser quenching meant the "fresh" Cy5.5-labeled nanoparticles were entering tumor, which confirmed the ultra-long circulating nanoparticles in blood could sustainedly irrigate to tumor. Our finding revealed the key mechanism by which ultra-long circulating NDDSs enhanced the tumor accumulation and retention, and provided experimental support for the development of ultra-long circulating delivery system in clinic.

[Application of nanocellulose in flexible sensors].

The shortage of medical resources promotes medical treatment reform, and smart healthcare is a promising strategy to solve this problem. With the development of Internet, real-time health status is expected to be monitored at home by using flexible healthcare systems, which puts forward new demands on flexible substrates for sensors. Currently, the flexible substrates are mainly traditional petroleum-based polymers, which are not renewable. As a natural polymer, cellulose, owing to its wide range of sources, convenient processing, biodegradability and so on, is an ideal alternative. In this review, the application progress of nanocellulose in flexible sensors is summarized. The structure and the modification methods of cellulose and nanocellulose are introduced at first, and then the application of nanocellulose flexible sensors in real-time medical monitoring is summarized. Finally, the advantages and future challenges of nanocellulose in the field of flexible sensors are discussed.

Improved antifouling properties of photobioreactors by surface grafted sulfobetaine polymers.

To improve the antifouling (AF) properties of photobioreactors (PBR) for microalgal cultivation, using trihydroxymethyl aminomethane (tris) as the linking agent, a series of polyethylene (PE) films grafted with sulfobetaine (PE-SBMA) with grafting density ranging from 23.11 to 112 µg cm-2 were prepared through surface-initiated atom transfer radical polymerization (SI-ATRP). It was found that the contact angle of PE-SBMA films decreased with the increase in the grafting density. When the grafting density was 101.33 µg cm-2, it reached 67.27°. Compared with the PE film, the adsorption of protein on the PE-SBMA film decreased by 79.84% and the total weight of solid and absorbed microalgae decreased by 54.58 and 81.69%, respectively. Moreover, the transmittance of PE-SBMA film recovered to 86.03% of the initial value after cleaning, while that of the PE film recovered to only 47.27%. The results demonstrate that the AF properties of PE films were greatly improved on polySBMA-grafted surfaces.

Rapid Gelling Chitosan/Polylysine Hydrogel with Enhanced Bulk Cohesive and Interfacial Adhesive Force: Mimicking Features of Epineurial Matrix for Peripheral Nerve Anastomosis.

Prompt and strong reconnection of severed peripheral nerves is crucial to nerve regeneration. The development of biocompatible nerve adhesives that are stronger than commonly used fibrin glue would be extremely beneficial to this field. We designed an in situ forming nerve adhesive hydrogel composed of chitosan and ε-polylysine (PL), which mimics the polysaccharides/protein structure of natural epineurium matrices, thus, enhancing the compatibility with nerves. Michael-type addition between the maleimide and thiol group was employed as a cross-linking reaction to eliminate foreign damage to nerves and to ensure a fast hydrogel formation speed (curing speed). Gelation occurred within 10 s, quick enough to promptly seal the transected nerve. Catechol groups conjugated onto PL molecules were demonstrated to reinforce both the bulk cohesive force of the hydrogel and the interfacial adhesive force between the hydrogel and epineurium. The storage modulus of the hydrogel was elevated to more than 2400 Pa. A superior nerve adhesion property that can tolerate 0.185 N of force (8× higher than fibrin glue) was obtained. After 8 weeks, the morphology of the repaired nerve fiber coapted by our hydrogel was very close to the morphology of normal nerve, and the axon cross ratio of the regenerated nerves coapted using hydrogel (57%) was much higher than employing the suture technique (35%). Thus, the in situ rapid gelling system offers a promising approach to the repair of severed peripheral nerves.

In situ formation of adhesive hydrogels based on PL with laterally grafted catechol groups and their bonding efficacy to wet organic substrates.

Adhesives with catechol moieties have been widely investigated in recent years. However, actually how much catechol groups for these mussel bio-inspired adhesives, especially in their natural form under physiological condition, is appropriate to bond with organic substrates has not been studied intensively. This study blends ε-polylysine (PL), featuring laterally grafted catechols under physiological conditions (pH 7.4), with oxidized dextran to form a hydrogel in situ via the Schiff base without introducing small cytotoxic molecules as crosslinking agents. It finds that the amount of catechol groups imposes an obvious influence on gelation time, swelling behavior, and hydrogel morphology. Both the storage modulus and adhesion strength are found to increase first and decrease afterwards with an increase of pendent catechol content. Furthermore, catechol hydrogen interactions and the decrease in the crosslink density derived from the decrease of amino groups on PL are simultaneously found to affect the storage modulus. Meanwhile, multiple hydrogen-bonding interactions of catechol with amino, hydroxyl, and carboxyl groups, which are in abundance on the surface of tissue, are mainly found to provide an adhesive force. The study finds that with more catechol, there is a greater chance that the cohesive force will weaken, making the entire adhesion strength of the hydrogel decrease. Using a cytotoxicity test, the nontoxicity of the hydrogel towards the growth of L929 cells is proven, indicating that hydrogels have potential applications in soft tissue repair under natural physiological conditions.

Multiple Non-Covalent Cross-Linked Multifunctional Strong Hemostatic Agent for Dynamic Exposure Hemostasis.

Trauma requires immediate hemostasis during primary care, as well as durable hemostasis that can withstand dynamic wound exposure. Although current hemostatic materials can treat bleeding sites in emergency situations, their mechanical strength and storage conditions limit their practical application. The simultaneous combination of good mechanical properties, storage stability, biocompatibility, and rapid hemostasis of hemostatic materials remains a challenge. In this paper, a novel hemostatic material based on multiple non-covalent bond crosslinking, which has excellent mechanical properties, good biocompatibility, storage stability, and rapid hemostasis ability, is reported. Under the drive of multiple non-covalent bonds, the flowability of hydrogel micro-modules (HM) decreases rapidly within 20 s after exposure to physiological saline. The HM form a gel barrier with a tensile strength of 62.10 kPa and an elongation at break of 1976% under multiple non-covalent bonding. Furthermore, the mechanical properties do not change significantly after 30 days of storage. Cell viability is maintained at over 80% after 3 days of incubation with the cells, and the hemolysis test shows a very low hemolysis rate (2.08%). The hemostatic gel formed by HM effectively prevents secondary bleeding in dynamic hemostasis experiments simulating transportation. This work provides a hemostatic material with comprehensive properties for practical applications.

Tissue-adhesive, stretchable and compressible physical double-crosslinked microgel-integrated hydrogels for dynamic wound care.

Integrated wound care through sequentially promoting hemostasis, sealing, and healing holds great promise in clinical practice. However, it remains challenging for regular bioadhesives to achieve integrated care of dynamic wounds due to the difficulties in adapting to dynamic mechanical and wet wound environments. Herein, we reported a type of dehydrated, physical double crosslinked microgels (DPDMs) which were capable of in situ forming highly stretchable, compressible and tissue-adhesive hydrogels for integrated care of dynamic wounds. The DPDMs were designed by the rational integration of the reversible crosslinks and double crosslinks into micronized gels. The reversible physical crosslinks enabled the DPDMs to integrate together, and the double crosslinked characteristics further strengthen the formed macroscopical networks (DPDM-Gels). We demonstrated that the DPDM-Gels simultaneously possess outstanding tensile (∼940 kJ/m3) and compressive (∼270 kJ/m3) toughness, commercial bioadhesives-comparable tissue-adhesive strength, together with stable performance under hundreds of deformations. In vivo results further revealed that the DPDM-Gels could effectively stop bleeding in various bleeding models, even in an actual dynamic environment, and enable the integrated care of dynamic skin wounds. On the basis of the remarkable mechanical and appropriate adhesive properties, together with impressive integrated care capacities, the DPDM-Gels may provide a new approach for the smart care of dynamic wounds. STATEMENT OF SIGNIFICANCE: Integrated care of dynamic wounds holds great significance in clinical practice. However, the dynamic and wet wound environments pose great challenges for existing hydrogels to achieve it. This work developed robust adhesive hydrogels for integrated care of dynamic wounds by designing dehydrated, physical double crosslinked microgels (DPDMs). The reversible and double crosslinks enabled DPDMs to integrate into macroscopic hydrogels with high mechanical properties, appropriate adhesive strength and stable performance under hundreds of external deformations. Upon application at the injury site, DPDM-Gels efficiently stopped bleeding, even in an actual dynamic environment and showed effectiveness in integrated care of dynamic wounds. With the fascinating properties, DPDMs may become an effective tool for smart wound care.

Epidermal growth factor-loaded, dehydrated physical microgel-formed adhesive hydrogel enables integrated care of wet wounds.

Integrated wound care, a sequential process of promoting wound hemostasis, sealing, and healing, is of great clinical significance. However, the wet environment of wounds poses formidable challenges for integrated care. Herein, we developed an epidermal growth factor (EGF)-loaded, dehydrated physical microgel (DPM)-formed adhesive hydrogel for the integrated care of wet wounds. The DPMs were designed using the rational combination of hygroscopicity and reversible crosslinking of physical hydrogels. Unlike regular bioadhesives, which consider interfacial water as a barrier to adhesion, DPMs utilize water to form desirable adhesive structures. The hygroscopicity allowed the DPMs to absorb interfacial water and subsequently, the interfacial adhesion was realized by the interactions between tissue and DPMs. The reversible crosslinks further enabled DPMs to integrate into hydrogels (DPM-Gels), thus achieving wet adhesion. Importantly, the water-absorbing gelation mode of DPMs enabled facile loading of biologically active EGF to promote wound healing. We demonstrated that the DPM-Gels possessed wet tissue adhesive performance, with about 40 times the wet adhesive strength of fibrin glue and about 4 times the burst pressure of human blood pressure. Upon application at the injury site, the EGF-loaded DPM-Gels sequentially promoted efficient wound hemostasis, stable sealing, and quick healing, achieving integrated care of wet wounds.

The Sequential and Systemic Administration of BMP-2 and SDF-1α Nanocapsules for Promoting Osteoporotic Fracture Healing.

OBJECTIVE: The objective of this study was to investigate the use of the nanocapsule sequential delivery of BMP-2 and SDF-1α through the peripheral circulatory system to promote the healing of osteoporotic fractures. METHODS: Based on increased vascular permeability in the early hematoma environment around the fracture and the presence of a large number of matrix metalloproteinase MMPs in the inflammatory environment, we designed MMP-sensitive nanocapsules which were formed viain situ free-radical polymerization on the surface of grow factors with 2-(methacryloyloxy) ethyl phosphorylcholine (MPC) and the bisacryloylated VPLGVRTK peptide. The antiphagic effect and biological activity of the growth factors for the nanomicrocapsule delivery system were tested by cell experiments. The 36 SD rats with an osteoporotic fracture model were randomly divided into six groups (A, B, C, D, E, and F). In this paper, the nanocapsules loaded with BMP-2 and SDF-1 are represented as n (BMP-2) and n (SDF-1α). In the six groups, the following different combinations of growth factors were injected into the bone defect site on days 1 and 3 after bone defect surgery: in group A, n (SDF-1α) combined with n (SDF-1α); in group B, n (BMP-2) combined with n (BMP-2); in group C, n (SDF-1α) + n (BMP-2) combined with n (SDF-1α) + n (BMP-2); in group D, n (SDF-1α) combined with n (BMP-2); in group E, n (BMP-2) combined with n (SDF-1α); in group F, nanocapsules without growth factor were used as the control group. Micro-CT was used to observe the effect of n(BMP-2) and n(SDF-1α) sequential delivery inearly healing in osteoporotic fractures. Finally, in this study, we evaluated the safety of the nanocapsules delivery system by detecting ectopic osteogenesis and inflammatory responses in animals. RESULTS: Nanocapsules have low toxicity and protect the integrity and biological activity of growth factors. The results confirmed that nanocapsules could still be effectively targeted to the fracture site on days 1, 3, and 7 after intravenous administration. Growth factors encapsulated in nanocapsules have better bone repair results than natural growth factors. In particular, groups C and D had the best bone repair results than other groups.In vivo experiments confirmed that nanocapsules did not cause significant ectopic osteogenesis and inflammation. CONCLUSION: The results confirmed that the special vascular permeability and inflammatory factor microenvironment of the fracture site could be used to deliver two growth factors with a synergistic effect through venous circulation, which could better promote the healing process of osteoporotic fracture.

SCIMP: A Novel Targeted Gene for Postmenopausal Osteoporosis Progression.

OBJECTIVE: The literature suggests that not all postmenopausal women suffer from osteoporosis, and the occurrence of postmenopausal osteoporosis is closely related to the genetic susceptibility of genes in the population and the cellular pathways of related genes. To systematically understand the functions of SCIMP gene for osteoporosis, both in vitro and in vivo experiments were analyzed in depth in this integrated study. METHODS: The significantly differentially expressed genes of postmenopausal osteoporosis (PMOP) patients from GEO database were selected. Meanwhile, the primary target gene was also confirmed in clinically recruited individuals using ELISA method; 50 postmenopausal osteoporosis patients with a T-score of -2.5 were randomly enrolled; postmenopausal women with a T-score > -2.5 were included in the non-osteoporotic group (including osteopenia and normal bone mineral density). The associated processes and signaling pathways were deeply investigated with GO and KEGG enrichment analysis. The downstream signaling factors including Erk-1/2, Akt, and IkB-related signaling pathways for the potential gene were evaluated using MG-63 cell line; the MTT, CCK-8, and flow cytometry assays were performed to exam MG-63 cell viability, proliferation, as well as apoptosis, respectively, under different treatments. RESULTS: Based on the differentially expressed gene analysis for GEO database, PMOP patients displayed 845 differentially expressed genes, including 709 down-regulated and 136 up-regulated ones. Ten genes including SCIMP were significantly differentially expressed (at least three-fold difference). SCIMP was the most markedly decreased in PMOP patients' specimens. Using clinical recruited individuals, the concentration of SCIMP was 96.6 ± 20.8 ng/µL in the PMOP group compared with 168.8 ± 23.5 ng/µL in the control group (p < 0.05). At the same time, the osteoclast differentiation signaling pathway was significantly up-regulated while hedgehogs as well as other signaling pathways were down-regulated based on the KEGG analysis. The phosphorylation level of Akt was markedly blocked in si-SCIMP treatment. Up-regulation of SCIMP increased cell proliferation, inhibited cell apoptosis, and enhanced cell viability in MG-63 cells, which was markedly rescued by AKT phosphorylation inhibitor. Finally, in vivo experiments also confirmed that the upregulation of SCIMP enhanced the structural parameters of rat trabecular bone and the osteogenic activity of bone tissue. CONCLUSION: SCIMP plays a critical role in the pathogenesis of postmenopausal osteoporosis in women. SCIMP influences osteoclasts function through an akt-dependent molecular pathway, and subsequently influences the equilibrium process of bone metabolism. This provides a new insight into the pathogenesis of postmenopausal osteoporosis as well as the clinical treatment of osteoporosis.

Highly stretchable, injectable hydrogels with cyclic endurance and shape-stability in dynamic mechanical environments, by microunit reformation.

Traditional injectable hydrogels have so far found it difficult to accommodate resistance to large deformation and shape-stability under cyclic deformation. Polyampholyte (PA) hydrogels exhibit resistance to large deformation, good fatigue-resistance and rapid self-healing under dynamic forces. The limitations of the preparation process result in non-injectability of polyampholyte (PA) hydrogels. Electrostatic interactions as a medium for resistance to large deformation and shape-stability after cyclic deformation in reformed injectable hydrogels has been explored in this study. The prepared hydrogels (as-prepared PA-N) were dried and smashed into microunits and then mixed with 0.9% NaCl solution to transform them into reformed hydrogels (as-reformed PA-N) via a needle to achieve injectability. The as-reformed PA-N could exhibit 913.6% elongation at break and showed shape-stability under cyclic deformation due to the efficient self-healing abilities of the microunits and the inherited structure of the prepared hydrogels, which are superior to those of current tough injectable hydrogels. Potential applications in elbow cyclic bending and frequent movement of mobile wounds have been proved in this study. Overall, the results showed that the as-reformed PA-N achieved convenient injectability with resistance to large deformation and shape-stability under cyclic deformation at the same time.

Microstructure-united heterogeneous sodium alginate doped injectable hydrogel for stable hemostasis in dynamic mechanical environments.

Injectable hydrogels that can withstand compressive and tensile forces hold great promise for preventing rebleeding in dynamic mechanical environments after emergency hemostasis of wounds. However, current injectable hydrogels often lack sufficient compressive or tensile performance. Here, a microstructure-united heterogeneous injectable hydrogel (MH) was constructed. The heterogeneous structure endowed MH with a unique "microstructures consecutive transmission" feature, which allowed it to exhibit high compressive and tensile performance simultaneously. In this work, two types of sodium alginate doped hydrogels with different microstructures were physically smashed into microgels, respectively. By mixing the microgels, MH with one micro-pores featured microstructure and another nano-pores featured microstructure can be formed. The obtained MH can withstand both compressive and tensile forces and showed high mechanical performance (compressive modulus: 345.67 ± 10.12 kPa and tensile modulus: 245.19 ± 7.82 kPa). Furtherly, MH was proven to provide stable and sustained hemostasis in the dynamic mechanical environment. Overall, this work provided an effective strategy for constructing injectable hydrogel with high compressive and tensile performance for hemostasis in dynamic mechanical environments.

Comprehensive and deep profiling of the plasma proteome with protein corona on zeolite NaY.

Proteomic characterization of plasma is critical for the development of novel pharmacodynamic biomarkers. However, the vast dynamic range renders the profiling of proteomes extremely challenging. Here, we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY. Specifically, zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY (NaY-PPC), followed by conventional protein identification using liquid chromatography-tandem mass spectrometry. NaY was able to significantly enhance the detection of low-abundance plasma proteins, minimizing the "masking" effect caused by high-abundance proteins. The relative abundance of middle- and low-abundance proteins increased substantially from 2.54% to 54.41%, and the top 20 high-abundance proteins decreased from 83.63% to 25.77%. Notably, our method can quantify approximately 4000 plasma proteins with sensitivity up to pg/mL, compared to only about 600 proteins identified from untreated plasma samples. A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states. In summary, this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.

Sequence-dependent synergistic inhibition of human glioma cell lines by combined temozolomide and miR-21 inhibitor gene therapy.

Down-regulation of microRNA-21 (miR-21) can induce cell apoptosis and reverse drug resistance in cancer treatments. In this study, we explored the most effective schedule of the miR-21 inhibitor (miR-21i) and Temozolomide (TMZ) combined treatment in human glioma cells. Three tumor cell lines, U251 phosphatase and tensin homologue (PTEN) mutant, LN229 (PTEN wild-type), and U87 (PTEN loss of function), were subjected to evaluate the antitumor effects of deigned treatments (a predose of miR-21i for 4/8 h and then a subsequent TMZ treatment, a predose of TMZ for 4/8 h and then a subsequent miR-21i treatment, or a concomitant treatment) in vitro. A synergistic antiproliferative and proapoptotic activity was only obtained in U251 and U87 cells when a predose was administered for 4 h before the treatment of the other therapeutic agent, while the best antitumor effect in LN229 cells was achieved by using the concomitant treatment. Our data indicate that the effect of sequence and timing of administration is dependent on the PTEN status of cell lines. The best suppression effect was achieved by a maximal inhibition of STAT3 and phosphorylated STAT3, in PTEN loss of function cells. Our results reveal that both the sequence and the timing of administration are crucial in glioma combination therapy.

Hollow poly(MPC-g-PEG-b-PLA) graft copolymer microcapsule as a potential drug carrier.

In this article, an amphiphilic graft copolymer composed of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) as the hydrophilic backbone, poly(L-lactic acid) (PLA) as the hydrophobic side-chains and polyethylene glycol (PEG) as the spacer was synthesized. Transmission electron microscopy revealed that the graft copolymer could self-assemble into hollow microcapsules when dialyzed in aqueous solution and particle sizes ranged from 200 to 300 nm, while the graft copolymer formed core-shell microspheres with the absence of PEG spacer. X-ray photoelectron microscope showed that MPC polymers were located at the surface of the microcapsules. The amounts of adsorbed bovine serum albumin and Fg on the microcapsules were significantly decreased than that on the conventional PLA particles (74% and 60%, respectively), well indicating the anti-adhesive property of the microcapsules. Paclitaxel was chosen as a prototype anticancer drug for the encapsulation and release studies, the results showed that the drug encapsulation efficiency was 89.3 ± 1.2% and the microcapsules exhibited controlled release behaviour.

Microgel-integrated, high-strength in-situ formed hydrogel enables timely emergency trauma treatment.

High-strength hydrogels formed in situ through a convenient gel transition process are highly desirable for emergency treatment due to their ability to quickly respond to accidents. However, current in-situ formed hydrogels require a laborious precursor preparation process or lack sufficient mechanical strength. Herein, we reported a series of microgels that were capable of convenient in-situ transition to high-strength hydrogels from their easily portable form, thereby facilitating emergency treatment. Three kinds of microgels were derived from two types of hydrogen bonds (H-bonds; OH⋯OC, NH⋯OC) crosslinked preformed hydrogels, and all exhibited excellent stability when stored at room temperature. After mixing with water, all these microgels could undergo a quick hydration process and then transform into high-strength hydrogels in situ through H-bonds. Specifically, stronger H-bond crosslinked microgels could build hydrogels with higher mechanical strength, albeit at the cost of longer hydration and operation time. Nevertheless, the whole operation process could be finished within several minutes, and the resultant hydrogels could exhibit maximally megapascal-level compressive strength and tens of kilopascal storage modulus. In the comparison of emergency application performance with commercial chitosan hemostatic powder (CHP), we found that the microgels could stop accidental bleeding almost immediately, and the whole process from taking out the stored microgels to hemostasis could be completed within 15 s, which was superior to CHP. Overall, the results indicated that the in-situ formed microgel-based hydrogels with convenient gel-transition ability and high strength showed great potential in emergency treatments.

Engineering Lipusu with lysophosphatidylcholine for improved tumor cellular uptake and anticancer efficacy.

Liposomes have been developed as drug delivery carriers to enhance the antitumor efficiency of therapeutic agents. Lipusu® (Lip), a paclitaxel (PTX) liposome, has been widely used in the treatment of breast cancer. Compared with PTX, Lip could change the biodistribution and reduce the systemic toxicity. However, there was no positive effect on the entry of PTX into tumor cells, and thus the therapeutic effect was not significantly improved. Therefore, it is meaningful to engineer Lip for improving tumor cellular uptake efficiency. Here, lysophosphatidylcholine (LPC)-engineered Lip (LPC-Lip) was constructed via inserting single chain lipid tails into liposomal lipid bilayers, which was realized by simple incubation. Compared with Lip, the better cellular uptake of liposomes modified with LPC resulted in enhanced cytotoxic activity of LPC-Lip in 4T1 cells. Furthermore, stronger tumor growth inhibition was observed in LPC-Lip treated 4T1 tumor-bearing mice without significant side effects. In conclusion, by modulating the lipid composition of Lip, the antitumor efficacy can be improved, and LPC engineered Lip may serve as a promising formulation of PTX for future cancer therapy.

Sequential Delivery of Different MicroRNA Nanocarriers Facilitates the M1-to-M2 Transition of Macrophages.

The early-stage repair of bone injuries dominated by the inflammatory phase is significant for successful bone healing, and the phenotypic transition of macrophages in the inflammatory phase plays indispensable roles during the bone healing process. The goal of this paper is to design a microRNA delivery nanocarrier for strictly temporal guidance of the polarization of macrophages by the sequential delivery of different microRNAs. The results showed that microRNA nanocarriers, synthesized through free radical polymerization, could be internalized by macrophages with about a cellular uptake efficiency of 80%, and the sequential delivery of microRNA-155 nanocarriers and microRNA-21 nanocarriers proved, for the first time, that it could promote an efficient and timely switch from the M1 to the M2 phenotype along the time point of bone tissue repair. The strategy proposed in this paper holds potential for controlling sequential M1-to-M2 polarization of macrophages, which provides another perspective for the treatment of bone tissue regeneration.