Epidermal growth factor-incorporated hydrogen bond crosslinked hemostatic microparticles capable of timely response to accidental bleeding for prehospital rescue.

Prehospital rescue of accidental massive bleeding is crucial for saving lives. However, currently available hemostatic materials are still in infancy in treating accidental bleeding due to the challenges in fully satisfying the complex outdoor hemostatic requirements. Herein, we designed an epidermal growth factor (EGF)- incorporated, microparticle-formed, high-strength, dynamic environment-stable hemostatic gel system for prehospital rescue.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Glioma-derived exosomes hijack the blood-brain barrier to facilitate nanocapsule delivery via LCN2.

Exosomes are small extracellular vehicles which could transport genetic materials and proteins between cells. Although there are reports about exosomes crossing the blood-brain barrier (BBB), the underlying mechanisms still need further study. We found that exosomes from primary brain tumors could upregulate the expression of Lipocalin-2 (LCN2) in bEnd.

Blood exosomes-based targeted delivery of cPLA2 siRNA and metformin to modulate glioblastoma energy metabolism for tailoring personalized therapy.

Background: Targeting glioblastoma (GBM) energy metabolism through multiple metabolic pathways has emerged as an effective therapeutic approach. Dual inhibition of phospholipid and mitochondrial metabolism with cytoplasmic phospholipase A2 (cPLA2) knockdown and metformin treatment could be a potential strategy. However, the strategic prerequisite is to explore a carrier capable of co-delivering the therapeutic combination to cross the blood-brain barrier (BBB) and preferentially accumulate at the GBM site.

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.

[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.

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.

"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.

An in situ catechol functionalized ε-polylysine/polyacrylamide hydrogel formed by hydrogen bonding recombination with high mechanical property for hemostasis.

In situ hydrogel has attracted widely attention in hemostasis due to its ability to match irregular defects, but its application is limited by insufficient mechanical strength and long gelation time. Although some specifical in situ chemically cross-linked hydrogels could be fast formed and exhibit high mechanical strength, they unable to absorb blood. Hence their applications were further limited in emergency hemostasis usage.

Early administration of MPC-n(IVIg) selectively accumulates in ischemic areas to protect inflammation-induced brain damage from ischemic stroke.

Ischemic stroke is an acute and severe neurological disease, which leads to disability and death. Immunomodulatory therapies exert multiple remarkable protective effects during ischemic stroke. However, patients suffering from ischemic stroke do not benefit from immunomodulatory therapies due to the presence of the blood-brain barrier (BBB) and their off-target effects.

Phosphatidylcholine-Engineered Exosomes for Enhanced Tumor Cell Uptake and Intracellular Antitumor Drug Delivery.

Exosomes derived from non-tumor cells hold great potential as drug delivery vehicles because of their good biosafety and natural transference of bioactive cargo between cells. However, compared to tumor-derived exosomes, efficient delivery is limited by their weak interactions with tumor cells. It is essential to engineer exosomes that improve tumor cellular internalization efficiency.

Preparation of cellulose nanospheres via combining ZnCl·3HO pretreatment and p-toluenesulfonic hydrolysis as a two-step method.

Spherical nanocelluloses, also known as cellulose nanospheres (CNS), have controllable morphology and have shown advantages as green template material, emulsion stabilizer. Herein, CNS were prepared via a new two-step method, first pretreatment of microcrystalline cellulose (MCC) using ZnCl·3HO and then acid hydrolysis of regenerated cellulose (RC) via p-toluenesulfonic acid (p-TsOH). The shape, size, crystallinity of MCC were changed, and nubbly RC with smallest size (942 nm) was obtained after 2 h pretreatment by ZnCl·3HO.

PMPC Modified PAMAM Dendrimer Enhances Brain Tumor-Targeted Drug Delivery.

The excellent biocompatibility drug delivery system for effective treatment of glioma is still greatly challenged by the existence of blood-brain barrier, blood-brain tumor barrier, and the tissue toxicity caused by chemotherapy drugs. In this study, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) is used for the first time for modifying third-generation poly(amidoamine) (PAMAM) to enhance their brain tumor-targeted drug delivery ability as well as simultaneously reducing the toxicity of PAMAM dendrimers and the tissue toxicity of the loaded doxorubicin (DOX). The cytotoxicity, the therapeutic ability in vitro, and the brain tumor-targeted ability of the PMPC modified PAMAM nanoparticles are further studied.

Erratum: Blood TfR+ exosomes separated by a pH-responsive method deliver chemotherapeutics for tumor therapy: Erratum.

[This corrects the article DOI: 10.7150/thno.37220.