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The proposed photoclick HC–HN bioink expands the palette of available polysaccharide-based bioinks and greatly extends the biofabrication window to broaden the application opportunities of 3D bioprinting.

Due to their inherent and tunable biomechanical and biochemical performances, bioactive hydrogels based on polysaccharides and peptides have shown attractive potential for wound management. In this review, the recent progress of bioactive hydrogels prepared by polysaccharides and peptides for soft tissue wound management is overviewed. Meanwhile, we focus on the elaboration of the relationship between chemical structures and inherent bioactive functions of polysaccharides and peptides, as well as the strategies that are taken for achieving multiple wound repairing effects including hemostasis, adhesion, wound contraction and closure, anti-bacteria, anti-oxidation, immunomodulation, molecule delivery

Three-dimensional (3D) bioprinting has played an increasingly crucial role in the manufacturing of organized complex tissues and organs, which has shown tremendous potential in the field of tissue engineering. Extrusion-based bioprinting takes advantage of its competitive pricing and flexibility to print various biomaterials, and it has now developed into one of the most used printing techniques. However, extruding soft hydrogels, also known as bioinks, often leads to poor fidelity when printed in air. As an emerging printing approach, 3D embedded bioprinting deposits bioinks not on a platform but into a support bath, preventing constructs from settling and collapsing. This review discusses the challenges faced in the traditional 3D bioprinting of soft or low-viscosity bioinks and the changes brought by embedded bioprinting as an emerging solution. Particular focus is given to the progress of hydrogels used as bioinks and support baths. Finally, we highlight the challenges involved in this process and look forward to the prospects of this technology.

Background Nanocarriers-derived antitumor therapeutics are often associated with issues of limited tumor penetration and dissatisfactory antitumor efficacies. Some multistage delivery systems have been constructed to address these issues, but they are often accompanied with complicated manufacture processes and undesirable biocompatibility, which hinder their further application in clinical practices. Herein, a novel dual-responsive multi-pocket nanoparticle was conveniently constructed through self-assembly and cross-linking of amphiphilic methoxypolyethylene glycol-lipoic acid (mPEG-LA) conjugates to enhance tumor penetration and antitumor efficacy. Results The multi-pocket nanoparticles (MPNs) had a relatively large size of ~ 170 nm at physiological pH which results in prolonged blood circulation and enhanced accumulation at the tumor site. But once extravasated into acidic tumor interstices, the increased solubility of PEG led to breakage of the supramolecular nanostructure and dissolution of MPNs to small-sized (3) bearing mice with reduced side effect. Conclusions Our facile fabrication of multi-pocket nanoparticles provided a promising way in improving solid tumor penetration and achieving a great therapeutic efficacy. Graphic Abstract

Congenital coagulation factor V (FV) deficiency is a very rare hemorrhagic disease with an incidence of approximately one in a million. The common clinical manifestations of FV deficiency include ecchymosis and mucosal bleeding. Life-threatening intracranial bleeding is rare. It has been reported in several cases. However, the molecular basis has been established in only a few cases.We reported a 2-month-old girl with congenital FV deficiency and intracranial hemorrhage. Coagulation screening combined with clinical manifestations was performed to diagnose congenital FV deficiency. Genetic testing was performed to identify the pathogenic genes. A literature review was included to emphasize the clinical manifestation, diagnosis, and treatment for congenital FV deficiency with intracranial bleeding.The coagulation tests revealed a significantly prolonged prothrombin time (PT) of 51 s and an activated partial thromboplastin time (APTT) of 73.7 s. The patient had a plasma FV activity of 0.9%. Genetic testing showed compound heterozygous mutations of the patient's FV gene. A literature review showed that patients with homozygous or compound heterozygous variants of the FV gene were often associated with a severe bleeding phenotype.Our study provides a direction for the rapid and accurate diagnosis and treatment for FV deficiency to avoid life-threatening bleeding. Infants with spontaneous cranial hematoma and intracranial hemorrhage should be investigated for underlying hemostatic defects. Congenital coagulation factor deficiency should be considered. Once congenital FV deficiency is diagnosed, fresh frozen plasma (FFP) should be given on a regular basis. Liver transplantation may be performed in severe cases.

Hongli Mao,1 Jinxiu Sheng,1 Jinlin Jia,1 Chang Wang,1 Shanfeng Zhang,2 Hongle Li,3 Fucheng He1 1Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2The Laboratory Center for Basic Medicine, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Fucheng HeDepartment of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People’s Republic of ChinaEmail hefucheng@zzu.edu.cnBackground: Solute carrier family 6 member 14 (SLC6A14) is a high-capacity amino acid transporter in mammalian cells. It has gained increasing attention for its potential involvement in the progression and metabolic reprogramming of various malignant tumors. However, the role of SLC6A14 in colorectal cancer (CRC) remains unclear.Methods: Real-time polymerase chain reaction (qRT-PCR), immunoblotting and immunohistochemistry were carried out to detect the expression level of SLC6A14 in human CRC tissues and CRC-derived cell lines. HCT-116 and Caco-2 cell lines were selected to conduct in vitro functional studies. Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, cell migration and invasion assays were performed to investigate the role of SLC6A14 in CRC cells. Besides, azoxymethane/dextran sulfate sodium salt (AOM/DSS)-induced CRC and tumor xenograft models were constructed to explore the effects of SLC6A14 blockade or overexpression during tumor progression in vivo.Results: SLC6A14 was substantially increased in human CRC samples and higher levels of SLC6A14 was correlated with advanced tumor stage, lymph node metastasis and dismal survival of CRC patients. SLC6A14 markedly promoted cell growth, inhibited cell apoptosis, and exacerbated migration and invasion of CRC cells in vitro. Mechanistically, SLC6A14 aggravated these malignant phenotypes through activating JAK2/STAT3 signaling pathway, and inhibiting JAK2/STAT3 signaling with specific inhibitors could reverse SLC6A14-mediated tumorigenic effects. Besides, two different animal studies verified the tumor-promoting effect of SLC6A14 in CRC.Conclusion: Our data illustrated the crucial function of SLC6A14 during CRC progression, suggesting SLC6A14/JAK2/STAT3 axis may serve as novel therapeutic targets for patients with CRC.Keywords: SLC6A14, colorectal cancer, CRC, proliferation, migration, STAT3

The development of natural polymer-based hydrogels, combining outstanding injectability, self-healing, and tissue adhesion, with mechanical performance, able to facilitate full-thickness skin wound healing, remains challenging. We have developed an injectable micellar hydrogel (AF127/HA-ADH/OHA-Dop) with outstanding adhesive and self-healing properties able to accelerate full-thickness skin wound healing. Dopamine-functionalized oxidized hyaluronic acid (OHA-Dop), adipic acid dihydrazide-modified HA (HA-ADH), and aldehyde-terminated Pluronic F127 (AF127) were employed as polymer backbones. They were cross-linked in situ using Schiff base dynamic covalent bonds (AF127 micelle/HA-ADH network and HA-ADH/OHA-Dop network), hydrogen bonding, and π-π stacking interactions. The resulting multicross-linked double-network design forms a micellar hydrogel. The unique multicross-linked double-network structure endows the hydrogel with both improved injection abilities and mechanical performance while self-healing faster than single-network hydrogels. Inspired by mussel foot adhesive protein, OHA-Dop mimics the catechol groups seen in mussel proteins, endowing hydrogels with robust adhesion properties. We also demonstrate the potential of our hydrogels to accelerate full-thickness cutaneous wound closure and improve skin regeneration with reduced scarring. We anticipate that our hydrogel platform based on a novel multicross-linked double-network design will transform the future development of multifunctional wound dressings.

3D bioprinting has been developed as a promising technology in a wide variety of biomedical applications. However, the successful implementation of bioprinting is still heavily restricted by the relatively narrow range of printable and biocompatible materials. Recently, many comprehensive reviews of the main bioprinting methods, commonly used bioprinting materials and the trending bioprinting applications have been carried out. In this review, we focused on the trends in the development of materials for 3D bioprinting. The significance and recent advances of ECM-based materials, multi-material and stimuli-responsive materials for bioprinting were summarized successively. Moreover, the challenges in current studies and future perspectives of materials for 3D bioprinting were discussed.

Although tissue adhesives have potential advantages over traditional sutures, existing ones suffer from several limitations: slow adhesion kinetic, low mechanical strength, and poor interfacial bonding with wet biological tissues. Herein, a cooperative mussel/slug double-bioinspired hydrogel adhesive (DBHA) composed of a robust adhesive interface and a stretchable dissipative matrix is developed. The DBHA is formed by a cationic polysaccharide (chitosan), an anionic polysaccharide (carboxymethyl cellulose), and a barbell-like dendritic lysine grafted with catechol groups (G3KPCA). Compared to various commercial bio-glues and traditional adhesives, the DBHA has significantly stronger tissue adhesion and enhanced toughness both ex vivo and in vivo. Meanwhile, the DBHA exhibits fast, strong, tough, and durable adhesion to diverse ex vivo tissue surfaces with blood. The adhesion energy between the adhesive and porcine skin can reach 200-900 J m

Photocrosslinked hydrogels show great potential as dressings for skin wound healing. However, most current hydrogels suffer from poor adhesion, toxic photoinitiators, and insufficient versatility. Therefore, developing novel hydrogel dressings with appropriate properties is of great importance to accelerate the wound healing process. In this study, we developed a polysaccharide-based dual-network hydrogel consisting of azide-functionalized carboxymethyl chitosan and o-nitrobenzyl-modified hyaluronic acid (CMC-AZ/HA-NB). The hydrogel showed excellent mechanical, tissue adhesion, and water retention properties. Controllable in situ photocrosslinking was carried out without photoinitiator, avoiding issues associated with the cytotoxicity of photoinitiators. An antibacterial agent-loaded hydrogel (CMC-AZ/HA-NB@D) showed enhanced antibacterial properties. In addition, the CMC-AZ/HA-NB@D hydrogel promoted collagen deposition and vascular formation, as well as reducing the expression of pro-inflammatory factors, thereby accelerating the wound healing process and improving skin regeneration. The present results highlight the promising potential of multifunctional photoinitiator-free polysaccharide hydrogels for application in wound dressings.

Hydrogel tissue adhesives that currently available are often fabricated by mixing two or more polymeric components. Single-component hydrogels afford injectability, strong and reversible adhesion remain a formidable challenge. This research describes the creation of the first single-component hyaluronic acid hydrogel adhesive-based on phenylboronic acid-diol ester linkages. Phenylboronic acid can not only serve as a cross-linker to form hydrogel, but also act as an adhesion site for glycosyl compounds found in biological cell membranes. The rheological and compressive tests for the hydrogel show that it has excellent self-healing properties, good injectability and strong compressive strength. Adhesion tests demonstrated that the hydrogel has significantly greater adhesion strength than commercial fibrin glue. These findings suggest that the rational design of hydrogel precursors facilitates the formation of single-component networks and multiple functionalities. In vivo studies further proved the hydrogel was an ideal bio-adhesive with biocompatibility, absorbed wound exudate and hemostasis, and accelerated wound closure.

Osteoporosis is a prevalent metabolic bone disease with low bone mass and degenerative disorders of bone tissues. Abnormal osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs) is involved in osteoporosis progression. Nevertheless, the underlying mechanisms for such event are still largely unknown. B7 family member B7H3 plays a critical role in regulating diverse cellular processes, but little is known about its effects on osteoporosis. In our present study, we found that B7H3 expression was down-regulated upon osteogenic induction, and remarkably decreased B7H3 expression was detected in bone marrow derived MSCs from ovariectomized (OVX) mice. Notably, we found that B7H3 conditional knockout (B7H3cKO) in bone marrow MSCs considerably strengthened bone mass in OVX-challenged mice. Loss-of-function experiments indicated that B7H3 ablation remarkably improved the osteogenic differentiation of MSCs both in vitro and in vivo, accompanied by restrained inflammatory response and NF-κB activation. Mechanistically, a direct association between B7H3 and AKT1 was detected. B7H3 deletion strongly up-regulated AKT1 activation in MSCs during osteogenic induction in vitro and in vivo. Further studies suggested that B7H3 knockdown-improved osteogenic differentiation was almost abolished by the blockage of AKT1 activation, demonstrating that B7H3-mediated osteogenic differentiation was largely AKT1-dependent. Together, our results concluded that B7H3 is a critical modulator for osteogenesis of MSCs, and can be a promising therapeutic target for osteoporosis treatment.

Artificial materials have no biological functions, but they are important for medical devices such as artificial organs and matrices for regenerative medicine. In this study, mitogenic and differentiation‐inducible materials are devised via the simple coating of polypeptides, which contain the sequence of epidermal growth factor or insulin‐like growth factor with a key amino acid (3,4‐dihydroxyphenylalanine) of underwater adhesive proteins. The adhesive polypeptides prepared via solid‐phase synthesis form layers on various substrates involving organic and inorganic materials to provide biological surfaces. Through the direct activation of cognate receptors on interactive surfaces, the materials enable increased cell growth and differentiation compared to that achieved by soluble growth factors. This superior growth and differentiation are attributed to the long‐lasting signal transduction (triggered by the bound growth factors), which do not cause receptor internalization and subsequent downregulation., 3,4‐dihydroxyphenylalanine‐containing peptides form bioactive layers on organic and inorganic material surfaces. On the adhesive growth factor nanolayers, cells receive long‐term biological signals from immobilized growth factors, leading to improved cell growth and differentiation.

Regulating the secretion and endothelial differentiation of human mesenchymal stem cells (hMSCs) plays an important role in the vascularization in tissue engineering and regenerative medicine. In this study, a recombinant cadherin fusion protein consisting of a human vascular endothelial-cadherin extracellular domain and immunoglobulin IgG Fc region (hVE-cad-Fc) was developed as a bioartificial matrix for modulating hMSCs. The hVE-cad-Fc matrix significantly enhanced the secretion of angiogenic factors, activated the VE-cadherin-VEGFR2/FAK-AKT/PI3K signaling pathway in hMSCs, and promoted the endothelial differentiation of hMSCs even without extra VEGF. Furthermore, the hVE-cad-Fc matrix was applied for the surface modification of a poly (lactic-co-glycolic acid) (PLGA) porous scaffold, which significantly improved the hemocompatibility and vascularization of the PLGA scaffold in vivo. These results revealed that the hVE-cad-Fc matrix should be a superior bioartificial ECM for remodeling the pro-vascularization extracellular microenvironment by regulating the secretion of hMSCs, and showed great potential for the vascularization in tissue engineering.

Combinatorial short interference RNA (siRNA) technology for the silencing of multiple genes is expected to provide an effective therapeutic approach for cancer with complex genetic mutation and dysregulation. Herein we present a tumor-activatable supramolecular nanoplatform for the delivery of siRNAs to target telomerase and telomeres for paclitaxel-resistant non-small-cell lung cancer (A549/PTX) treatment. Two different sequences of siRNA are incorporated in a single nanoparticle, which is obtained by self-assembly from a peptide dendrimer. The siRNA stability is improved by the nanoparticle in the presence of serum compared to free siRNA, and these siRNAs are protected from RNA enzyme degradation. In the tumor extracellular acid environment, the PEG corona of the nanoparticle is removed to promote the internalization of siRNAs into tumor cells. The disulfide linkages between the nanoparticle and siRNAs are cleared in the reductive environment of the tumor cells, and the siRNAs are released in the cytoplasm. In vitro experiments show that the gene expression of hTERT and TRF2 at the mRNA and protein levels of A549/PTX tumor cells is down-regulated, which results in cooperative restraining proliferation and invasion of A549/PTX tumor cells. For the tumor cell-targeting function of the MUC1 aptamer and the EPR effect, sufficient tumor accumulation of nanoparticles was observed. Meanwhile, a shift of negative surface charge of nanoparticles to positive charge in the tumor extracellular microenvironment enhances deep penetration of siRNA-incorporating nanoparticles into tumor tissues. In vivo animal studies support that successful down-regulation of hTERT and TRF2 gene expression achieves effective inhibition of the growth and neovascularization of drug-resistant tumor cells. This work has provided a new avenue for drug-resistant cancer treatment by designing and synthesizing a tumor-activatable nanoplatform to achieve the delivery of dual-gene targeted combinatorial siRNAs.

Morphology genetic biomedical materials (MGBMs), referring to fabricating materials by learning from the genetic morphologies and strategies of natural species, hold great potential for biomedical applications. Inspired by the cargo-carrying-bacterial therapy (microbots) for cancer treatment, a MGBM (artificial microbots, AMBs) was constructed. Rather than the inherent bacterial properties (cancerous chemotaxis, tumor invasion, cytotoxicity), AMBs also possessed ingenious nitric oxide (NO) generation strategy. Mimicking the bacterial construction, the hyaluronic acid (HA) polysaccharide was induced as a coating capsule of AMBs to achieve long circulation in blood and specific tissue preference (tumor tropism). Covered under the capsule-like polysaccharide was the combinatorial agent, the self-assembly constructed by the amphiphilic dendrons with abundant l-arginine residues peripherally (as endogenous NO donor) and hydrophobic chemotherapeutic drugs at the core stacking on the surface of SWNTs (the photothermal agent) for a robust chemo-photothermal therapy (chemo-PTT) and the elicited immune therapy. Subsequently, the classic inducible nitric oxide synthase (iNOS) pathway aroused by immune response was revolutionarily utilized to oxidize the l-arginine substrates for NO production, the process for which could also be promoted by the high reactive oxygen species level generated by chemo-PTT. The NO generated by AMBs was intended to regulate vasodilation and cause a dramatic invasion (as the microbots) to disperse the therapeutic agents throughout the solid tumor for a much more enhanced curative effect, which we defined as "self-propulsion". The self-propelled AMBs exhibiting impressive primary tumor ablation, as well as the distant metastasis regression to conquer the metastatic triple negative breast cancer, provided pioneering potential therapeutic opportunities, and enlightened broad prospects in biomedical application.

Ischemia/reperfusion (I/R) is a well-known injury to the myocardium, but the mechanism involved remains elusive. In addition to the well-accepted apoptosis theory, autophagy was recently found to be involved in the process, exerting a dual role as protection in ischemia and detriment in reperfusion. Activation of autophagy is mediated by mitochondrial permeability transition pore (MPTP) opening during reperfusion. In our previous study, we showed that MPTP opening is regulated by VDAC1, a channel protein located in the outer membrane of mitochondria. Thus, up-regulation of VDAC1 expression is a possible trigger to cardiomyocyte autophagy via an unclear pathway. Here, we established an anoxia/reoxygenation (A/R) model in vitro to simulate the I/R process in vivo. At the end of A/R treatment, VDAC1, Beclin 1 and LC3-II/I were up-regulated, and autophagic vacuoles were increased in cardiomyocytes, which showed a connection of VDAC1 and autophagy development. These variation also led to ROS burst, mitochondrial dysfunction and aggravated apoptosis. Knockdown of VDAC1 by RNAi could alleviate the above-mentioned cellular damages. Additionally, the expression of PINK1 and Parkin were enhanced after A/R injury. Furthermore, Parkin was recruited to mitochondria from the cytosol, which suggested that the PINK1/Parkin autophagic pathway was activated during A/R. Nevertheless, the PINK1/Parkin pathway was effectively inhibited when VDAC1 was knocked-down. Taken together, the A/R-induced cardiomyocyte injury was mediated by VDAC1 up-regulation, which led to cell autophagy via the PINK1/Parkin pathway, and finally aggravated apoptosis. This article is protected by copyright. All rights reserved.

Additional file 1: Fig. S1. 1H NMR spectrum (400 MHz) of mPEG-LA conjugates in CDCl3. Fig. S2. SEM image (A), size (B) and zeta potential (C) of the self-assembly of mPEG-LA conjugates (NPs, 100 g mL−1). Fig. S3. Size distribution of MPNs at different concentrations. Fig. S4. Fluorescence spectra of a mixed solution of NPs (100 μg mL−1)and MPNs (100 μg mL−1) prepared with 0.1 wt% DiO/DiI tracing the development of FRET between two dyes. Fig. S5. Critical aggregation concentration of MPNs at (A) pH 7.4 or (B) 6.5. Fig. S6. Fluorescence spectra of a mixed solution of MPNs (100 μg mL−1, pH 6.5) prepared with 0.1 wt% DiO/DiI tracing the development of FRET between two dyes over time. Fig. S7. Flow cytometric histogram profiles of 4T1 cells treated with MPNs, DOX, D-NPs and D-MPNs for 3 h (DOX concentration: 10 μg mL−1). Fig. S8. CLSM images of 4T1 cells incubated with DOX, D-NPs, D-MPNs and DOX·HCl for 1 h (DOX dosage: 2 μg mL−1). Hoechst 33342 was used to stain the cell nuclei. Scale bar: 10 μm. Fig. S9. Quantitative assessment of penetration of DOX formulations into 4T1 cells. The cells were incubated with DOX, D-NPs and D-MPNs at a DOX concentration of 5 μg mL−1 for 2 h. Fig. S10. IOD (Integrated optical density) of immunohistochemical images for saline, MPNs, DOX·HCl, D-NPs and D-MPNs groups. The apoptotic rates of tumor sections based on TUNEL images (A), tumor microvessel density based on CD31 images (B) and Ki67 positive cells (C) of tumor sections were calculated with Image-Pro Plus 6.0 software. Data were presented as mean ± SD (n = 3), *p < 0.01, **p < 0.005. Fig. S11. Body weight changes of 4T1-bearing BALB/c mice after administration with saline, MPNs, DOX·HCl, D-NPs and D-MPNs (n = 8, dosage: 5 mg DOX kg−1 mouse body weight, *p < 0.01). The arrows indicated the time points for intravenous injection. Fig. S12. Routine blood analysis results of the mice collected on the 12th day after intravenous injection of saline, MPNs, DOX·HCl, D-NPs or D-MPNs. The results show mean and standard deviation of white blood cells (WBCs), red blood cell (RBC), hemoglobin (HGB) and platelets (PLT). Fig. S13. Histological examination of major organs separated from 4T1-bearing BALB/c mice after administration with saline, MPNs, DOX·HCl, D-NPs and D-MPNs for 18 days. Scale bar: 100 μm. Fig. S14. TUNEL staining of heart (×200) of 4T1-bearing BALB/c mice after administration with saline, MPNs, DOX·HCl, D-NPs and D-MPNs for 18 days. The apoptotic cells (red arrow) and normal cells were stained brown and blue, respectively. Table S1. Pharmacokinetic parameters of DOX·HCl, D-NPs and D-MPNs after intravenous administration at an equivalent dose of 10 mg DOX/kg mouse body weight (n = 3 per group).

Effective wound dressings are of great significance in preventing infections and promoting wound healing. However, most existing hydrogel dressings have an inadequacy in either mechanical performance, biological activities, or versatilities. Here we presented a double-network cross-linked polysaccharide-based hydrogel composed of collagen peptide-functionalized carboxymethyl chitosan (CS) and oxidized methacrylate sodium alginate (SA). The hydrogel possessed interconnected porous morphologies, suitable swelling ratios, excellent mechanical properties, and favorable biocompatibility. Meanwhile, the in vivo studies using a mouse full-thickness skin defect model showed that the double-network CS/SA hydrogel significantly accelerated wound healing by regulating the inflammatory process, promoting collagen deposition, and improving vascularization. Therefore, the functionalized double-network hydrogel should be a potential candidate as wound dressings.

Vascular endothelial growth factors (VEGFs) play an important role in tissue repair and regeneration. In this study, VEGFs were immobilised by photo-reactive gelatine by photo-irradiation and the effect of immobilisation was quantitatively investigated. Immobilised VEGFs enhanced endothelial cell migration and growth more than soluble VEGFs. In addition, the activation effects depended on the VEGF isoforms. Prolonged activation of phosphorylation sites in the VEGF receptor, which is associated with migration and proliferation, was observed on the immobilised VEGF surfaces. The results indicated that photo-immobilised VEGFs induced high cell activation by stimulating phosphorylation of the VEGF receptor, VEGFR2, which activated multiple cell functions.

Origami research is always devoted to exploring the transformation from a paper-like material into a three-dimensional (3D) object, which is widely used in the storage of planar structures. However, origami only has a two-dimensional crease map, so it performs limited effect on the storage of 3D surface. Inspired by waterbomb origami, this paper presents a scheme of folding discretized surfaces of revolution to create foldable 3D geometries. The geometries, which are the approximation of target surfaces of revolution, consist of discretizing surfaces of revolution and have 3D crease maps to guide folding. The discretized surfaces constructed by the approaching scheme can satisfy the error requirements and retain the features of original surfaces. The paper verifies the feasibility of the folding scheme by showing the formula of four typical surfaces, including convex shape, concave shape, concave-convex shape and capsule shape. This scheme of folding discretized surfaces of revolution shows the potential of origami to 3D deployable structures in the field of aerospace.

Due to the inconvenience of application, risk of extra damage to fragile soft tissues, and the high incidence of late-stage complications, significant research endeavors have been focused on developing safe and effective bioadhesives to replace or assist the traditional suture techniques for wound closure. Here, we describe a fast and high strength bioadhesive based on polysaccharides and peptide dendrimers (OCMC/G3KP) with inherent hemostatic ability and antibacterial properties. Compared with the commercial bioadhesive Coseal, the OCMC/G3KP hydrogel shows a remarkable 5-fold increase in adhesion strength. The in vivo studies further confirm the superior wound healing performance of the OCMC/G3KP hydrogel in contrast with Coseal and conventional sutures. The OCMC/G3KP hydrogels are efficient and biocompatible bioadhesives with precise controllability that could be flexibly modulated to meet diverse clinical demands.

An integrated gene nanovector capable of overcoming complicated physiological barriers in one vector is desirable to circumvent the challenges imposed by the intricate tumor microenvironment. Herein, a nuclear localization signals (NLS)-decorated element and an iRGD-functionalized element based on O-carboxymethyl chitosan were synthesized, mixed, and coated onto PEI/DNA to fabricate bacterium-mimicking sequentially targeted therapeutic nanocomplexes (STNPs) which were internalized through receptor-mediated endocytosis and other pathways and achieved nuclear translocation of DNA. The endo/lysosomal membrane disruption triggered by reactive oxygen species (ROS) after short-time illumination, together with the DNA nuclear translocation, evoked an enhanced gene expression. Alternatively, the excessive ROS from long-time irradiation induced apoptosis in tumor cells, bringing about greater anti-tumor efficacy owing to the integration of gene and photodynamic therapy. Overall, these results demonstrated bacterium-mimicking STNPs could be a potential candidate for tumor treatments.

In vitro expansion of human mesenchymal stem cells (hMSCs) using serum-free culture medium is important for basic research and clinical applications. It is known that some growth factors are required for developing a defined medium for hMSC culture. However, growth factors usually show poor stability, short circulating half-life and a rapid rate of cellular internalization when they are in a diffusible state. A potential way to overcome these problems is to immobilize growth factors on materials. Here, three different types of growth factors, basic fibroblast growth factor, transforming growth factor-beta, and platelet-derived growth factor, were co-immobilized on cell culture dish surfaces by photo-reactive gelatin and used for serum-free hMSC cultures. The results showed that the immobilized growth factors supported cell proliferation similarly to the serum-containing medium. More importantly, the immobilization of growth factors significantly improved their thermal stability and efficiently prolonged their shelf life at 4 °C and 37 °C. Furthermore, the immobilized growth factors could be reused at least three times without losing their stimulation effect on cell proliferation. This photo-reactive gelatin-based immobilization of growth factors appears to be a promising method for serum-free hMSC culturing.