Tumor acidification and GSH depletion by bimetallic composite nanoparticles for enhanced chemodynamic therapy of TNBC.

Chemodynamic therapy (CDT) based on intracellular Fenton reaction to produce highly cytotoxic reactive oxygen species (ROS) has played an essential role in tumor therapy. However, this therapy still needs to be improved by weakly acidic pH and over-expression of glutathione (GSH) in tumor microenvironment (TEM), which hinders its future application. Herein, we reported a multifunctional bimetallic composite nanoparticle MnO2@GA-Fe@CAI based on a metal polyphenol network (MPN) structure, which could reduce intracellular pH and endogenous GSH by remodeling tumor microenvironment to improve Fenton activity. MnO2 nanoparticles were prepared first and MnO2@GA-Fe nanoparticles with Fe3+ as central ion and gallic acid (GA) as surface ligands were prepared by the chelation reaction. Then, carbonic anhydrase inhibitor (CAI) was coupled with GA to form MnO2@GA-Fe@CAI. The properties of the bimetallic composite nanoparticles were studied, and the results showed that CAI could reduce intracellular pH. At the same time, MnO2 could deplete intracellular GSH and produce Mn2+ via redox reactions, which re-established the TME with low pH and GSH. In addition, GA reduced Fe3+ to Fe2+. Mn2+ and Fe2+ catalyzed the endogenous H2O2 to produce high-lever ROS to kill tumor cells. Compared with MnO2, MnO2@GA-Fe@CAI could reduce the tumor weight and volume for the xenograft MDA-MB-231 tumor-bearing mice and the final tumor inhibition rate of 58.09 ± 5.77%, showing the improved therapeutic effect as well as the biological safety. Therefore, this study achieved the high-efficiency CDT effect catalyzed by bimetallic through reshaping the tumor microenvironment.

iRGD mediated pH-responsive mesoporous silica enhances drug accumulation in tumors.

The limited penetration of nanocarriers into tumors and the slow release of drugs from these carriers to tumor cells are significant challenges in cancer therapy. In this study, we developed a novel drug delivery carrier derived from mesoporous silica, dually modified with the tumor-homing cyclic peptide iRGD (CRGDKGPDC) and the pH-responsive polymer poly(2-ethyl-2-oxazoline) (PEOz) for treating triple-negative breast cancer. The carrier selectively bound to the αvß3 integrin receptor, which is specifically expressed in MDA-MB-231 breast cancer cells and vessels. Subsequently, it penetrated deep into the tumor parenchyma through NRP-1 receptor-dependent internalization, with the drug-loaded particles releasing drugs rapidly in the acidic cytoplasmic environment. Results indicated that the drug release rate of PEOz-modified formulations was pH-dependent. Lysosomal escape experiments demonstrated that PEOz-modified particles efficiently escaped lysosomes to release drugs. In vitro cytotoxicity assays revealed that iRGD-functionalized particles were more cytotoxic to NRP-1-positive MDA-MB-231 cells compared to NRP-1-negative MCF-7 cells. Cellular uptake studies demonstrated that iRGD mediated enhanced endocytosis of nanoparticles into MDA-MB-231 cells. In vitro tumor cell spheroid penetration assays confirmed that the PEOz and iRGD dual-modified carrier facilitated deeper distribution of DOX in multicellular spheroids compared to free DOX. Moreover, in a nude mouse model of triple-negative breast cancer, the dual-modified drug-loaded carrier significantly inhibited tumor growth without inducing weight loss or liver and kidney damage. This dual-modified mesoporous silica presents a novel and promising delivery carrier for enhancing cancer treatment.

C-Reactive Protein-Albumin Ratio (CAR): A More Promising Inflammation-Based Prognostic Marker for Patients Undergoing Curative Hepatectomy for Hepatocellular Carcinoma.

Background: Systemic inflammatory response is a hallmark of cancer and plays a significant role in the development and progression of various malignant tumors. This research aimed to estimate the prognostic function of the C-reactive protein-albumin ratio (CAR) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC) and compare it with other inflammation-based prognostic scores, including the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, monocyte-lymphocyte ratio, systemic immune inflammation index, prognostic index, Glasgow prognostic score, and modified Glasgow prognostic score. Methods: Retrospective analysis was conducted on data from 1039 HCC cases who underwent curative liver resection. The prognostic performance of CAR was compared with other scores using the area under the time-dependent receiver operating characteristic (t-ROC) curve. Multivariable Cox regression analyses were performed to confirm independent predictors for disease-free survival (DFS) and overall survival (OS). Results: The area under the t-ROC curve for CAR in the evaluation of DFS and OS was significantly greater than that of other scores and alpha-fetoprotein (AFP). Patients were stratified based on the optimal cut-off value of CAR, and the data revealed that both DFS and OS were remarkably worse in the high-CAR set compared to the low-CAR set. Multivariable Cox analysis demonstrated that CAR was an independent prognostic parameters for assessing DFS and OS. Regardless of AFP levels, all patients were subsequently divided into significantly different subgroups of DFS and OS based on CAR risk stratification. Similar results were observed when applying CAR risk stratification to other scoring systems. CAR also showed good clinical applicability in patients with different clinical features. Conclusion: CAR is a more effective inflammation-based prognostic marker than other scores and AFP in predicting DFS as well as OS among patients with HCC after curative hepatectomy.

Curcumin-loaded chitosan-based hydrogels accelerating S. aureus-infected wound healing.

The damaged skin for some reasons is vulnerable to invasion by bacteria and other harmful microorganisms, leading to delay of the wound healing. In order to promote the infected wound healing, curcumin was loaded with chitosan-based hydrogel was formed through phenylborate ester bonding and its properties and effects on the S. aureus-infected wound healing was tested. It was found the hydrogel showed good antioxidation on the intracellular reactive oxygen species, inhibition on the growth of S. aureus, and acceleration the infected skin healing. The ablity of hydrogel due to its regulating inflammation, promoting angiogenesis and collagen synthesis in the wound site. This research work suggested that the developed multifunctional hydrogel might be a beneficial treatment for the infected wound healing.

Preparation and Hemostatic Effect of Micro-Nanograded Porous Particles Doped with Dopamine-Based Water-Triggered Intelligent Composite Adhesives.

The wet environment of water or tissue in bleeding wounds poses significant challenges to the adhesion performance of existing hemostatic adhesives. An intelligent composite adhesive prepared by doping starch-based silicate micro-nanograded porous particles (MBC@CMS) with dopamine-hyperbranched polymers (HPD, 7800 Mw) synthesized by the Michael addition reaction could be triggered by water to form a glue (MBC@CMS-HPD). The results indicated that MBC@CMS-HPD could still have adhesion properties under running water washing and water immersion and could effectively seal the water outlet. The results of the glue-forming mechanism showed that MBC@CMS-HPD had better wettability than water, which could eliminate water molecules at the wet adhesive surface. When contacted with water, the agglomeration of the HPD hydrophobic chain increases the exposure of the catechol group, and the relative atomic mass of the N element on the surface increases from 2.8 to 4.8%. The adhesion of MBC@CMS-HPD was enhanced and stable. MBC@CMS-HPD showed significant hemostasis effects in five injury bleeding models of Sprague-Dawley (SD) rats and New Zealand rabbits. Especially in the fatal femoral artery bleeding model of New Zealand rabbits, MBC@CMS-HPD reduced the amount of bleeding by 75% and shortened the bleeding time by 78% compared with the a-cyanoacrylate adhesives. The results of the coagulation mechanism showed that compared with HPD, MBC@CMS-HPD could activate both endogenous and exogenous coagulation pathways. Among them, after contact with blood, HPD formed a gel to close the blood outlet, and MBC@CMS entered the wound to activate the internal and external coagulation pathways. In addition, HPD and MBC@CMS had good histocompatibility and degradability, which has the potential to be applied to different wounds.

Photocatalytic Ag/AgBr-MBG for Rapid Antibacterial and Wound Repair.

In daily life and during surgery, the skin, as the outermost organ of the human body, is easily damaged to form wounds. If the wound was infected by the bacteria, especially the drug-resistant bacteria such as methicillin-resistant staphylococcus aureus (MRSA), it was difficult to recover. Therefore, it was important to develop the safe antimicrobial strategy to inhibit bacterial growth in the wound site, in particular, to overcome the problem of bacterial drug resistance. Here, the Ag/AgBr-loaded mesoporous bioactive glass (Ag/AgBr-MBG) was prepared, which had excellent photocatalytic properties under simulated daylight for rapid antibacterial activity within 15 min by generating reactive oxygen species (ROS). Meanwhile, the killing rate of Ag/AgBr-MBG against MRSA was 99.19% within 15 min, which further reduced the generation of drug-resistant bacteria. In addition, Ag/AgBr-MBG particles could disrupt bacterial cell membranes, showing the broad-spectrum antibacterial properties and promoting tissue regeneration and infected wound healing. Ag/AgBr-MBG particles might have potential applications as a light-driven antimicrobial agent in the field of biomaterials.

Smart microneedle patches for wound healing and management.

The number of patients with non-healing wounds is generally increasing globally, placing a huge social and economic burden on every country. The complexity of the wound-healing process remains a major health challenge despite the numerous studies that have been reported on conventional wound dressings. Therefore, a therapeutic system that combines diagnostic and therapeutic modalities is essential to monitor wound-related biomarkers and facilitate wound healing in real time. Microneedles, as a multifunctional platform, are promising for transdermal diagnostics and drug delivery. Their advantages are mainly reflected in painless transdermal drug delivery, good biocompatibility, and ease of self-administration. In this work, we review recent advances in the use of microneedle patches for wound healing and monitoring. The paper first provides a brief overview of the skin structure and the wound healing process, and then discusses the current state of research and prospects for the development of wound-related biomarkers and their real-time monitoring based on microneedle sensors. It summarizes the current state of research based on the unique design of microneedle patches, including biomimetic, conductive, and environmentally responsive, to achieve wound healing. It further summarizes the prospects for the application of different microneedle-based drug delivery modalities and drug delivery substances for wound healing, due to their superior transdermal drug delivery advantages. It concludes with challenges and expectations for the use of smart microneedle patches for wound healing and management.

Chitosan and hyaluronic-based hydrogels could promote the infected wound healing.

The most important function of skin is to prevent biological dehydration and protect internal structures from the environment. When a wound becomes infected, the bacteria cause a sustained inflammatory response at the infected site, further delaying the healing process. Therefore, the search for better antibacterial strategies has become a topic of great concern. Therefore, the development of multifunctional hydrogels with antibacterial properties, ROS removal, and hemostasis is urgently required for promoting wound healing process. Chitosan is the only cationic natural polysaccharide with good biocompatibility, antibacterial and hemostatic ability. It is a candidate material to prepare hydrogel wound dressing. Hyaluronic acid (HA) is a natural biological macromolecule that belongs to a group of heteropolysaccharides known as non-sulfated glycosaminoglycans. It is a major component of the skin extracellular matrix (ECM) and is involved in inflammation, angiogenesis, and tissue regeneration. Here, the hydrogel was designed with the natural macromolecular of the gallic acid-grafted quaternized chitosan (GA-QCS) and oxidized hyaluronic acid (OHA) via Schiff base and/or Michael addition reaction. It was found that the GA-QCS/OHA hydrogel exhibited multifunctional capabilities with injectable, hemostasis, degradation, and release of medicines. In addiation, GA-QCS/OHA hydrogels exhibited remarkable antioxidant and migration promoting effects in vitro. And the mupirocin-loaded GA-QCS/OHA hydrogels had inhibitory effects on E. coli (Gram-negative bacterium) and S. aureus (Gram-positive bacterium) in vitro. A full-thickness skin of S. aureus infection mouse wound model was used to test the bioactive effect of the hydrogels and the accelerated wound healing was obtained due to the inhibiting the proinflammatory factor TNF-α and upregulating the vascularization factor CD31. This study proposed an effective strategy based on antioxidant, antibacterial, self-healing multifunctional hydrogel for wound healing under various infectious complications. This natural macromolecular hydrogel could act as an effective reactive oxygen species scavenger to promote the wound healing in the future.

Application of a Dual-Probe Coloading Nanodetection System in the Process Monitoring and Efficacy Assessment of Photodynamic Therapy: An In Vitro Study.

The oxygen-consuming property of photodynamic therapy (PDT) affects its effects and aggravates tumor hypoxia, thus upregulating the vascular endothelial growth factor (VEGF) to exacerbate tumor metastasis and lead to treatment failure. Therefore, it is necessary to monitor the dynamic changes in the factors related to PDT and tumor development trends in real time, thus helping to improve PDT efficiency. This study fabricated a fluorescent probe, TPE-2HPro, and a fluorescein-labeled aptamer probe, FAM-AptamerVEGF, to detect hydrogen peroxide (H2O2) and VEGF through the photoinduced electron-transfer effect and the specific affinity of the aptamer to VEGF, respectively. The two probes were loaded into the inner pores and absorbed on the surface of polydopamine coating-wrapped mesoporous silica nanoparticles (MSN@PDA) to construct the dual-probe-loaded system, MSNTH@PDAApt, which was kept stable in fetal bovine serum (FBS) solution and achieved pH-responsive release behavior, thus helping to increase the accumulation of the two probes in tumor cells. The dichloroacetic acid-mediated in vitro antitumor tests showed that the changing trends of H2O2 and VEGF levels were consistent with the results of related mechanism studies and could be monitored by MSNTH@PDAApt. The in vitro chlorin e6 (Ce6)-mediated PDT treatment demonstrated that when the illumination condition was 650 nm, 50 mW/cm2 for 10 min, cells were more inclined to metastasis and invasion rather than death due to a substantial increase in VEGF expression at the low Ce6 concentrations. With the increase of the Ce6 concentration, the growth of the H2O2 level gradually exceeded that of VEGF, and the reactive oxygen species (ROS)-mediated cell death dominated when the Ce6 concentration was about 2 times its IC50 values. Besides, hypoxia also affected the H2O2 and VEGF changes. These results demonstrated that MSNTH@PDAApt could precisely monitor and assess the tumor development trends during PDT treatment, thus helping improve the treatment effect.

Reoxygenation Modulates the Adverse Effects of Hypoxia on Wound Repair.

Hypoxia is a major stressor and a prominent feature of pathological conditions, such as bacterial infections, inflammation, wounds, and cardiovascular defects. In this study, we investigated whether reoxygenation has a protective effect against hypoxia-induced acute injury and burn using the C57BL/6 mouse model. C57BL/6 mice were exposed to hypoxia and treated with both acute and burn injuries and were in hypoxia until wound healing. Next, C57BL/6 mice were exposed to hypoxia for three days and then transferred to normoxic conditions for reoxygenation until wound healing. Finally, skin wound tissue was collected to analyze healing-related markers, such as inflammation, vascularization, and collagen. Hypoxia significantly increased inflammatory cell infiltration and decreased vascular and collagen production, and reoxygenation notably attenuated hypoxia-induced infiltration of inflammatory cells, upregulation of pro-inflammatory cytokine levels (IL-6 and TNF-α) in the wound, and remission of inflammation in the wound. Immunofluorescence analysis showed that reoxygenation increased the expression of the angiogenic factor α-SMA and decreased ROS expression in burn tissues compared to hypoxia-treated animals. Moreover, further analysis by qPCR showed that reoxygenation could alleviate the expression of hypoxic-induced inflammatory markers (IL-6 and TNF), increase angiogenesis (SMA) and collagen synthesis (Col I), and thus promote wound healing. It is suggested that oxygen can be further evaluated in combination with oxygen-releasing materials as a supplementary therapy for patients with chronic hypoxic wounds.

Oxygen-releasing hydrogels promote burn healing under hypoxic conditions.

Hypoxic nonhealing wounds are a common complication in chronic patients, and chronic hypoxia is the main reason for delayed wound healing, so local wound oxygenation may be an effective way to address this problem. Here, we proposed a system consisting of oxygen-releasing microsphere (GC) and self-healing hydrogel (QGO). QGO/GC hydrogel could promote survival, migration and tube formation of human umbilical vein endothelial cells under hypoxic conditions. Moreover, QGO/GC hydrogels exhibited biocompatibility in vitro and in vivo. The hypoxic mouse burn model further confirmed that QGO/GC hydrogel could promote tissue repair by reducing inflammation (TNF-α and IL-1ß), increasing angiogenesis (CD31, VEGF and α-SMA) and collagen deposition. This study provided an effective oxygen-releasing hydrogel that could offer a simple and effective method for the clinical treatment of chronic hypoxic wounds. STATEMENT OF SIGNIFICANCE: Burn injury is caused by various exogenous factors such as friction, cold, radiations, electricity, chemicals, hot surfaces or liquids. Severe burn can damage the entire skin layer, and the healing process is delayed due to an unbalanced inflammatory response, excessive reactive oxygen species, lack of angiogenesis (insufficient nutrient and oxygen availability), and susceptibility to infection. In the present study, we proposed an oxygen-releasing hydrogel (QGO/GC). QGO/GC hydrogel could promote survival, migration, and tube formation of human umbilical vein endothelial cells under hypoxic conditions. And QGO/GC hydrogels could promote tissue repair by reducing inflammation, increasing angiogenesis and collagen deposition. This work provided an effective oxygen-releasing hydrogel for the clinical management of chronic hypoxic wounds.

Recent molecular design strategies for efficient photodynamic therapy and its synergistic therapy based on AIE photosensitizers.

Cancer seriously endangers human life and health. Recently, the development of AIEgens with aggregation-induced emission (AIE) effect as a new generation of photosensitizers (PSs) to circumvent aggregation-induced fluorescence quenching and reduction of ROS generation has received extensive attention in photodynamic therapy (PDT), a non-invasive anticancer therapy. Rational molecular design can enhance the photosensitization of AIE PSs to achieve effective PDT and can realize the construction of functionalized AIE PSs and synergistic therapy based on AIE PSs. To improve the efficacy of AIE PSs for cancer treatment, many groups have conducted molecular design studies and produced exciting results. This review summarizes the molecular design strategies of three types of AIE PSs for effective photodynamic therapy, focusing on the design strategies of pure organic small molecule type AIE PSs, and reviews the existing design strategies of metal complexes and conjugated polymers. Subsequently, the design strategy to achieve synergistic treatment of AIE PSs from molecular modifications is summarized. The challenges and prospects of the AIE PSs research field are further discussed.

Application of Metal-Organic Framework in Diagnosis and Treatment of Diabetes.

Diabetes-related chronic wounds are often accompanied by a poor wound-healing environment such as high glucose, recurrent infections, and inflammation, and standard wound treatments are fairly limited in their ability to heal these wounds. Metal-organic frameworks (MOFs) have been developed to improve therapeutic outcomes due to their ease of engineering, surface functionalization, and therapeutic properties. In this review, we summarize the different synthesis methods of MOFs and conduct a comprehensive review of the latest research progress of MOFs in the treatment of diabetes and its wounds. State-of-the-art in vivo oral hypoglycemic strategies and the in vitro diagnosis of diabetes are enumerated and different antimicrobial strategies (including physical contact, oxidative stress, photothermal, and related ions or ligands) and provascular strategies for the treatment of diabetic wounds are compared. It focuses on the connections and differences between different applications of MOFs as well as possible directions for improvement. Finally, the potential toxicity of MOFs is also an issue that we cannot ignore.

Multifunctional nanosystems sequentially regulating intratumor Fenton chemistry by remodeling the tumor microenvironment to reinforce chemodynamic therapy.

The particularity of the tumor microenvironment (TME) significantly limits the efficiency of chemodynamic therapy (CDT). Although various measures have been taken to improve the efficiency of CDT, how to organically integrate them into one nanosystem to achieve efficient synergy for CDT according to predetermined procedures is still an urgent problem to be solved. This work reported a multifunctional nanosystem, TPI@PPCAI, which comprised the inner triphenylphosphine modified D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS-PPh3) micelles loading iron-oxide nanoparticles (IONs), and the outer poly (dopamine-co-protocatechuic acid) (PDA-PA, PP) coating modified with carbonic anhydrase IX inhibitor (CAI). TPI@PPCAI remodeled TME by sequential function adjustment to make it suitable for the efficient Fenton reactions: CAI first inhibited the overexpressed CA IX to result in intracellular acidification, which combined with near-infrared light (NIR) irradiation to accelerate the PP coating degradation, thereby promoting the exposure and disintegration of the inner micellar structure to release TPGS-PPh3 and IONs. The TPGS-PPh3 further elevated the intracellular ROS basal level by targeting and interfering with the mitochondrial function. Therefore, the TME was transformed into an acidic microenvironment with high ROS levels, which vigorously promoted the Fenton reaction mediated by IONs with the aid of photothermal effect induced by PP coating via NIR irradiation, ultimately earning high-efficiency CDT on xenograft MDA-MB-231 tumor-bearing mice. This study improved the efficiency of Fenton reaction in biological systems through the practical design of nanostructures and provided a novel thought for ROS-mediated therapy.

Research Progress on Improving the Efficiency of CDT by Exacerbating Tumor Acidification.

In recent years, chemodynamic therapy (CDT) has received extensive attention as a novel means of cancer treatment. The CDT agents can exert Fenton and Fenton-like reactions in the acidic tumor microenvironment (TME), converting hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (·OH). However, the pH of TME, as an essential factor in the Fenton reaction, does not catalyze the reaction effectively, hindering its efficiency, which poses a significant challenge for the future clinical application of CDT. Therefore, this paper reviews various strategies to enhance the antitumor properties of nanomaterials by modulating tumor acidity. Ultimately, the performance of CDT can be further improved by inducing strong oxidative stress to produce sufficient ·OH. In this paper, the various acidification pathways and proton pumps with potential acidification functions are mainly discussed, such as catalytic enzymes, exogenous acids, CAIX, MCT, NHE, NBCn1, etc. The problems, opportunities, and challenges of CDT in the cancer field are also discussed, thereby providing new insights for the design of nanomaterials and laying the foundation for their future clinical applications.

The contribution of pore size and porosity of 3D printed porous titanium scaffolds to osteogenesis.

Porous titanium implants were popularly fabricated to promote bone formation. A desirable porous scaffold was recommended to be with porosity of >60% or/and pore size of >300 µm for better osteointegration. However, whether the pore size and porosity could be randomly selected within the recommended values? And what is the correlation between pore size and porosity for accelerating osteointegration? In this study, porous titanium with cubic cell structure was produced by selective laser melting. The designed porosities of scaffolds with 700-µm pore size were 40%, 70% and 90%; and the pore sizes of scaffolds with 70% porosity were 400, 700 and 900 µm. The in vitro osteogenic potential and in vivo bone formation were investigated. Results showed that porosity and pore size could be tuned by altering strut size, which was further directly responsible for mechanical properties. Besides, pore size and porosity synergistically contributed to osteogenic activity in vitro and new bone formation in vivo. In regard to pore sizes herein, the optimized one for better osteogenic response and bone forming ability was ~600-700 µm (p70). Too smaller or too larger pore size might more or less hinder cellular behaviors and bone regeneration, even if both pore size (300-900 µm) and porosity (70%) were within the recommended value range. At a constant pore size (~600-700 µm), p70 and p90 with higher porosity was more conductive to biological effects, compared with p40. As a result, pore-size variation revealed more significant influence on osteogenesis, compared with variation of porosity within recommended values. However, the applicable porosity within recommended values should be designed with the consideration of specific load-bearing conditions. This study helps to provide guidance for designing porous scaffolds with appropriate mechanical strengths and effective bone-forming ability, so as to develop better custom-made bone substitutes.

Degradable and self-luminescence porous silicon particles as tissue adhesive for wound closure, monitoring and accelerating wound healing.

Tissue adhesives have received much attention for their effectiveness in sealing wounds or incisions in clinical surgery, especially in minimally invasive surgery. To meet the safe and smart wound management requirements, ideal tissue adhesives are expected to have high biocompatibility, and be able to accelerate wound closing and healing, and monitor wound healing process. However, few adhesives fit all of the above descriptions. It has been demonstrated that inorganic nanoparticles can directly glue biological tissue based on nano-bridging effect. In this study, self-luminescence porous silicon (LPSi) particles were prepared with degradable and biocompatible properties. In addition, the self-luminescence property of LPSi particles was discovered by In Vivo Imaging System (IVIS) for the first time, which can avoid the limitations of photoluminescence imaging. Due to the oxidation and degradation reaction, LPSi particles not only can be degraded completely in several days, but also showed satisfactory biocompatibility. And their degradation product could promote tube formation of HUVECs. Moreover, owing to the high specific surface area and the outer oxide layer of LPSi particles, LPSi tissue adhesive exhibited strong adhesive strength to pig livers. Furthermore, this adhesive closed wound rapidly, promoted angiogenesis and epidermal regeneration, and facilitated wound healing in a mouse skin incision model. Importantly, the wound healing ratio can be monitored by measuring the self-luminescence intensity of LPSi particles in the wound site. This study reveals that LPSi particles could be employed as a safe and smart wound management tissue adhesive for wound closure, as well as accelerating and monitoring wound healing.

Co-culture of BMSCs and HUVECs with simvastatin-loaded gelatin nanosphere/chitosan coating on Mg alloy for osteogenic differentiation and vasculogenesis.

Mg alloys are increasingly being investigated as a versatile and economical alternative for developing bone repair implants because of their high mechanical strength, wide availability, adjustable structure and properties. In this study, magnesium alloy WE43 is coated on both sides with gelatin nanosphere/chitosan (GNs/CTS), a coating enhanced by incorporating simvastatin (SIM). SIM-loaded GNs/CTS coated magnesium alloy can promote the osteogenic differentiation of bone mesenchymal stem cells (BMSCs). BMSCs and human umbilical vein endothelial cells (HUVECs) are co-cultured through transwell systems. The release of SIM from the coating is found to increase the secretion of chemokine and angiogenic factors from BMSCs, which promote the migration and tube formation of HUVECs, respectively. Bone morphogenetic protein secreted by HUVECs is seen to increase by the release of SIM from the coating, promoting the osteogenic differentiation of BMSCs. The secretion of chemokines from HUVECs promote the migration of BMSCs. The coated magnesium alloy substrate loaded with SIM is found to regulate the osteogenic differentiation of BMSCs. The study of the paracrine interaction between BMSCs and HUVECs proves that the applied coating promotes both osteogenic differentiation and vascularization, thus demonstrating a new approach for the design of bone repair materials based on magnesium alloys.

Gelatin-based adhesive hydrogel with self-healing, hemostasis, and electrical conductivity.

As a kind of natural protein derived material, gelatin has been widely used in the preparation of medical hydrogels due to its good biocompatibility, non-immunogenicity and the ability of promoting cell adhesion. Functionalization of gelatin-based hydrogels is a hot topic in research and its clinic application. Herein, a novel gelatin-based adhesive hydrogel was prepared via mussel-inspired chemistry. Gelatin was firstly functionalized by dopamine to form dopamine grafted gelatin (GelDA). After the mixture with 1,4-phenylenebisboronic acid and graphene oxide (GO), the GelDA/GO hydrogels were obtained by H2O2/HRP (horseradish peroxidase) catalytic system. Based on the self-healing and tissue adhesion of the hydrogels, the hemostatic property has been exhibited in the rat hepatic hemorrhage model. Additionally, the incorporation of GO endowed conductivity and enhanced the mechanical property of GelDA/GO hydrogels. The electromyography (EMG) signals of finger movement were successfully monitored by using hydrogel as the adhesive electrodes of EMG monitor. L929 cell experiments showed that the hydrogels had good cytocompatibility. The results indicated the potential application of GelDA/GO hydrogels in tissue adhesives, wound dressings, and wearable devices.

Study on hemostatic effect and mechanism of starch-based nano-microporous particles.

The powdered hemostatic particles have broad application prospects in large open wounds, internal organ injuries and penetrating injuries of the body. In this study, nanoscale mescoporous and macroporous silica (MMSN), nanoscale mescoporous and macroporous bioactive glass (MBG), micron-scale cross-linked corn starch porous microspheres (CMS), MMSN@CMS and MBG@CMS starch-based nano-microporous particles were synthesized and their hemostatic effect and hemostatic mechanism were studied. The results showed that comparted with the single particle of CMS, the combination particles MBG@CMS and MMSN@CMS significantly increased the water absorption rate, activated both internal and external coagulation pathways, significantly shortened CBT, as well as the improved hemostatic effects in vitro. The immediately released Ca2+ from MBG@CMS in the blood to participate in the coagulation pathway, and MMSN@CMS activated platelets by concentrating blood coagulation factors, might be the main hemostatic mechanisms for the starch-based nano-microporous particles. Furthermore, the hemostatic efficacy of particles, both in the model of tail-amputation and liver injury in SD rats, showed the starch-based nano-microporous particles, especial MBG@CMS, could significantly reduce the weight of blood loss and shorten the bleeding time. Our research work stated that the starch-based nano-microporous particles MBG@CMS might be a hemostasis biomaterial with the potential applications for the emergency bleeding.