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For general dynamic positioning systems, controllers are mainly based on the feedback of motions only in the horizontal plane. However, for marine structures with a small water plane area and low metacentric height, undesirable surge and pitch oscillations may be induced by the thruster actions. In this paper, three control laws are investigated to suppress the induced pitch motion by adding pitch rate, pitch angle or pitch acceleration into the feedback control loop. Extensive numerical simulations are conducted with a semi-submersible platform for each control law. The influences of additional terms on surge—pitch coupled motions are analyzed in both frequency and time domain. The mechanical constraints of the thrust allocation and the frequency characters of external forces are simultaneously considered. It is concluded that adding pitch angle or pitch acceleration into the feedback loop changes the natural frequency in pitch, and its performance is highly dependent on the frequency distribution of external forces, while adding pitch rate into the feedback loop is always effective in mitigating surge—pitch coupled motions.

As conventional treatments for diabetic wounds often fail to achieve rapid satisfactory healing, the development of effective strategies to accelerate diabetic wound repair is highly demanded. Herein, fibroblast growth factor 21 (FGF21) and metformin co-loaded multifunctional polyvinyl alcohol (PVA) hydrogel were fabricated for improved diabetic wound healing. The in vitro results proved that the hydrogel was adhesive and injectable, and that it could particularly scavenge reactive oxygen species (ROSs), while the in vivo data demonstrated that the hydrogel could promote angiogenesis by recruiting endothelial progenitor cells (EPCs) through upregulation of Ang-1. Both ROSs’ removal and EPCs’ recruitment finally resulted in enhanced diabetic wound healing. This work opens a strategy approach to diabetic wound management by combining biological macromolecules and small chemical molecules together using one promising environmental modulating drug delivery system.

Psoriasis is an autoimmune inflammatory disease which is fundamentally different from dermatitis. Its treatments include topical medications and systemic drugs depending on different stages of the disease. However, these commonly used therapies are falling far short of clinical needs due to various drawbacks. More precise therapeutic strategies with minimized side effects and improved compliance are highly demanded. Recently, the rapid development of biomaterial-based therapies has made it possible and promising to attain topical psoriasis treatment. In this review, we briefly describe the significance and challenges of the topical treatment of psoriasis and emphatically overview the latest progress in novel biomaterial-based topical therapies for psoriasis including microneedles, nanoparticles, nanofibers, and hydrogels. Current clinical trials related to each biomaterial are also summarized and discussed.

Efficient reconstruction of a fully functional skin after wounds requires multiple functionalities of wound dressing due to the complexity of healing. In these regards, topical administration of functionalized nanoparticles capable of sustainably releasing bioactive agents to the wound site may significantly accelerate wound repair. Among the various nanoparticles, superparamagnetic iron oxide (Fe3O4) nanoparticles gain increasing attractiveness due to their intrinsic response to an external magnetic field (eMF). Herein, based on the Fe3O4 nanoparticle, we developed a fibroblast growth factor (bFGF)-loaded Fe3O4 nanoparticle using a simple mussel-inspired surface immobilization method. This nanoparticle, named as bFGF-HDC@Fe3O4, could stabilize bFGF in various conditions and exhibited sustained release of bFGF. In addition, an in vitro study discovered that bFGF-HDC@Fe3O4 could promote macrophage polarization toward an anti-inflammatory (pro-healing) M2 phenotype especially under eMF. Further, in vivo full-thickness wound animal models demonstrated that bFGF-HDC@Fe3O4 could significantly accelerate wound healing through M2 macrophage polarization and increased cell proliferation. Therefore, this approach of realizing sustained the release of the growth factor with magnetically macrophage regulating behavior through modification of Fe3O4 nanoparticles offers promising potential to tissue-regenerative applications.

Growth factors (GFs) have been well known for their therapeutic effects on wound healing. Due to their vulnerable biostability, biomaterial carriers are usually used to deliver GFs to maintain their bioactivity. Among the carriers, PEG hydrogels are the most widely applied. But the uncontrolled release of GFs and their immunogenicity dramatically retard the application of PEG hydrogels as carriers of GFs. Herein, FGF2 loaded zwitterionic sulfobetaine methacrylate (SBMA) hydrogels were developed, and it was revealed that these hydrogels were more effective in delivering FGF2 for wound healing than were PEG hydrogels. In vitro studies demonstrated that SBMA hydrogels could successfully prolong the release of FGF2, which effectively maintained the bioactivity of FGF2. Further in vivo investigation showed that SBMA hydrogels could efficiently accelerate wound regeneration by promoting granulation tissue formation, collagen deposition, cell proliferation and migration, reepithelialization and angiogenesis. All results validated that SBMA hydrogels were promising substituents of PEG hydrogels for delivering FGF2 for wound regeneration.

Lower extremity arterial disease (LEAD) is a major vascular complication of diabetes. Vascular endothelial cells dysfunction can exacerbate local ischemia, leading to a significant increase in amputation, disability, and even mortality in patients with diabetes combined with LEAD. Therefore, it is of great clinical importance to explore proper and effective treatments. Conventional treatments of diabetic LEAD include lifestyle management, medication, open surgery, endovascular treatment, and amputation. As interdisciplinary research emerges, regenerative medicine strategies have provided new insights to treat chronic limb threatening ischemia (CLTI). Therapeutic angiogenesis strategies, such as delivering growth factors, stem cells, drugs to ischemic tissues, have also been proposed to treat LEAD by fundamentally stimulating multidimensional vascular regeneration. Recent years have seen the rapid growth of tissue engineering technology; tissue-engineered biomaterials have been used to study the treatment of LEAD, such as encapsulation of growth factors and drugs in hydrogel to facilitate the restoration of blood perfusion in ischemic tissues of animals. The primary purpose of this review is to introduce treatments and novel biomaterials development in LEAD. Firstly, the pathogenesis of LEAD is briefly described. Secondly, conventional therapies and therapeutic angiogenesis strategies of LEAD are discussed. Finally, recent research advances and future perspectives on biomaterials in LEAD are proposed.

Fundamental understanding of specific interactions of human islet amyloid polypeptide (hIAPP) with cell membrane is critical for elucidating the underlying pathogenesis of type II diabetes mellitus (T2DM). Membrane cholesterol is known to regulate membrane functions and properties, but its exact role in driving hIAPP-membrane interactions still remains controversial. In this work, we computationally investigated the concentration effect of cholesterol on the adsorption, orientation, and surface interaction of hIAPP oligomers on POPC bilayers containing different amounts of cholesterol (χ = 0, 20, and 40 mol %). Collective MD simulations consistently showed that an increased cholesterol level modulated the structure and dynamics of POPC bilayer, leading to an increase of bilayer thickness, lipid packing order, and surface hydrophobicity but a decrease of lipid mobility. Cholesterol-induced bilayer changes further caused hIAPP oligomer to more preferentially bind to POPC bilayer in the presence of cholesterol via C-terminal residues, in contrast to weak or no binding of hIAPP oligomer on pure POPC bilayers. The cholesterol-enhanced hIAPP-membrane binding is mainly contributed by electrostatic interactions between C-terminal residues and lipid head groups, which may explain the rapid adsorption and aggregation of hIAPP in the presence of cholesterol in cell membranes. This computational work provides some insights into drug development and therapeutic strategies for T2DM by considering cholesterol effects.

Thruster-assisted position mooring (PM) systems use both mooring lines and thrusters to maintain the position and heading of marine structures in ocean environments. In order to operate in an energ...

The float-over installation method has become the best solution to offshore heavy topsides installations due to its flexibility and low cost. Dynamically positioned vessels can accurately keep posi...

Development of biocompatible and bioactive drug-loaded sutures is considered as an effective but challenging strategy for the wound healing process by delivering biological drugs (e.g., antibiotics) or growth factors (e.g., bFGF) at the surgical wound sites. Conventional offline suture strategies often lead to fast and uncontrollable release of drugs at wound sites, rendering wound healing to become a longer and painful process for patients. Herein, we propose an online suture strategy to fabricate electrospun polycaprolactone (PCL) fibrous yarns, incorporated with both collagen (COL) and bFGF, to produce bFGF-COL@PCL sutures. Upon demonstrating the well-oriented and aligned fibrous microstructure, high mechanical properties, and controlled release of bFGF from bFGF-COL@PCL sutures in vitro, we then applied bFGF-COL@PCL sutures to an incision wound healing mouse model

Topical wound dressings with various silver compositions that exhibit effective bacterial inhibition properties are often used to treat infected wounds. However, a silver dressing with no bioactive functionality will typically delay subsequent wound repair processes. Therefore, development of a simple wound dressing containing silver and loaded with a bioactive drug is a very attractive solution. Herein, we developed a silver crosslinked injectable chitosan-silver hydrogel as a silver immobilization matrix, loaded with basic fibroblast growth factor (bFGF) as its cargo (namely, bFGF@CS-Ag) for treatment of both acute and infected wounds. The in vivo results showed that bFGF@CS-Ag significantly enhanced infectious wound regeneration compared to that of acute wounds. Further investigation demonstrated that the improved wound repair by bFGF@CS-Ag was ascribed to the effectiveness of bacterial inhibition, the promotion of granulation formation, collagen deposition, neovascularization and re-epithelization, and to the reduction of the inflammatory response through promotion of M2 macrophage polarization. These results proved that the immobilization of silver in the hydrogel not only reduced the side effects of silver on the bioactivity of bFGF but also allowed elution of bFGF in a controlled release manner. Thus, this novel system has promising therapeutic potential for topical treatment of wounds.

Successful dermal wound regeneration requires the coordination of repair cells and cellular signals with the extracellular matrix (ECM), which serves as an indispensable mechanical and biological supporter for cell functions and communications with varied cytokines during healing processes. Here, we developed an injectable bioactive wound dressing, methacrylated hyaluronic acid (Me-HA)-based hydrogel loading with basic fibroblast growth factor (bFGF), endowing the dressing with the pleiotropic bioactivity to mimic natural ECM. This bFGF@Me-HA dressing was applied to a mouse with full-thickness excisional wounds to investigate its positive roles in wound repair owing to the complementary functions of HA with sustained release of bioactive bFGF. Compared with the single Me-HA and bFGF group, bFGF@Me-HA hydrogel dressings significantly enhanced wound healing with accelerated re-epithelialization, granulation formation, collagen, deposition and skin appendage regeneration. Further investigations showed significantly promoted cell proliferation and vascularization in the bFGF@Me-HA group, which was mediated by the upregulation of transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) expressions. In conclusion, this bFGF@Me-HA hydrogel realized the optimization of simple ECM mimic dressing via introducing the bioactive effector, bFGF, and has the potential to be widely used as an effective bioactive ECM-based wound dressing in future wound care.

Protein‐based hydrogels have attracted great attention due to their excellent biocompatible properties, but often suffer from weak mechanical strength. Conventional strengthening strategies for protein‐based hydrogels are to introduce nanoparticles or synthetic polymers for improving their mechanical strength, but often compromise their biocompatibility. Here, a new, general, protein unfolding‐chemical coupling (PNC) strategy is developed to fabricate pure protein hydrogels without any additives to achieve both high mechanical strength and excellent cell biocompatibility. This PNC strategy combines thermal‐induced protein unfolding/gelation to form a physically‐crosslinked network and a ‐NH2/‐COOH coupling reaction to generate a chemicallycrosslinked network. Using bovine serum albumin (BSA) as a globular protein, PNC‐BSA hydrogels show macroscopic transparency, high stability, high mechanical properties (compressive/tensile strength of 115/0.43 MPa), fast stiffness/toughness recovery of 85%/91% at room temperature, good fatigue resistance, and low cell cytotoxicity and red blood cell hemolysis. More importantly, the PNC strategy can be not only generally applied to silk fibroin, ovalbumin, and milk albumin protein to form different, high strength protein hydrogels, but also modified with PEDOT/PSS nanoparticles as strain sensors and fluorescent fillers as color sensors. This work demonstrates a new, universal, PNC method to prepare high strength, multi‐functional, pure protein hydrogels beyond a few available today.

Pressure ulcer (PU) in patients with diabetes mellitus (DM) is still a clinical intractable issue due to the complicated physiological characteristics by the prolonged high glucose level and impaired angiogenesis. The PU treatment includes surgical debridement, stem cell therapy and growth factors, leading to high cost and repeated professional involvement. Developing effective wound dressing combining the therapeutic cells and growth factors has become highly demanded. Herein, we reported the direct subcutaneous administration of endothelial progenitor cells (EPCs) and acid fibroblast growth factor (aFGF) with a shape-memorable methacrylated gelatin cryogel (EPCs/aFGF@GelMA) for the therapy of PU in rats with DM. This EPCs/aFGF@GelMA cryogel system presented microporous structure, elastic mechanical strength and enhanced cell migration property with controlled release of aFGF. Moreover, compared with EPCs/aFGF and GelMA alone, in vivo results showed that this EPCs/aFGF@GelMA system exhibited accelerated wound closure rate, enhanced granulation formation, collagen deposition as well as re-epithelization. Importantly, we found that the excellent positive performance of EPCs/aFGF@GelMA is due to its up-regulation of HIF-ɑ upon the wound site, modulating the microenvironment of wound site to initiate the impaired local angiogenesis. Collectively, this hybrid gelatin cryogels show great promise for biomedical applications, especially in tissue engineering and regenerative medicine.

Thruster-assisted position mooring (PM) systems use both mooring lines and thrusters for station keeping of marine structures in ocean environments. To operate in an energy-efficient manner in moderate sea conditions, setpoints need to be appropriately chosen for the setpoint controller, so that the mooring system counteracts main environmental loads, while the thrusters reduce oscillatory motions of the marine structure. In this paper, reinforcement learning is used to design a decision-making agent for setpoint selection. In particular, a deep deterministic policy gradient (DDPG) approach is adopted with the powerful actor–critic architecture to continuously modify the setpoint setting at an optimal position. Extensive numerical experiments demonstrated that with the DDPG-based PM system, the intelligent agent is able to successfully identify the optimal positioning region in an unknown and stochastic environment, and the power consumption of the thrusters is maintained at a considerably low level.

Axon retraction greatly limits functional recovery after spinal cord injury (SCI) and neuron polarization, which affects processes including axon formation and development, is a promising target for promoting axon regeneration. Increasing microtubule stability has been demonstrated to improve intrinsic axon regeneration processes and is critically related to endoplasmic reticulum (ER)-mitochondria interactions. We used real-time polymerase chain reaction, Western blotting, and immunofluorescence to screen a variety of natural compounds, and found that Loureirin B (LrB) effectively promoted neuron polarization and axon regeneration in vitro and in vivo. LrB significantly inhibited ER stress and thereby promoted mitochondrial functions by regulating mitochondrial fusion. Further, LrB reactivated the Akt/GSK-3β pathway, which plays critical roles in cell survival and microtubule stabilization. Taken together, our results suggest that the effects of LrB on neuron regeneration involve the inhibition of ER stress-induced mitochondrial dysfunction and activation of the Akt/GSK-3β pathway, which further promotes microtubule stabilization. LrB may therefore be a promising candidate for facilitating recovery following SCI.

For dynamic positioning systems, a three degree-of-freedom motion control in the horizontal plane has usually been regarded as adequate for practical applications. However, for marine structures with a small water-plane area and low metacentric height, unintentional surge–pitch coupled motion will be induced by thruster actions. To effectively mitigate the thruster-induced pitch motion, we first apply a pitch damping controller for the dynamic positioning of a semisubmersible platform. Quantitative studies are conducted to select the optimal control coefficient for this damping controller, and its influence on surge–pitch coupled motion is analyzed theoretically and numerically. Furthermore, a novel adaptive fuzzy damping controller is proposed to improve the pitch mitigating effect. The fuzzy controller takes low-frequency pitch angle and pitch rate as inputs, and outputs time-varying damping control coefficient through fuzzy inference. Comparisons are made between the fixed damping controller and the proposed fuzzy damping controller. Finally, a parametric analysis is conducted to investigate the influence of the maximum damping control coefficient on pitch motion. The overall simulation results show that the proposed fuzzy damping controller has better performance than the fixed damping controller.

Although aberrant alveolar myofibroblasts (AMYFs) proliferation and differentiation are often associated with abnormal lung development and diseases, such as bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF), epigenetic mechanisms regulating proliferation and differentiation of AMYFs remain poorly understood. Protein arginine methyltransferase 7 (PRMT7) is the only reported type III enzyme responsible for monomethylation of arginine residue on both histone and nonhistone substrates. Here we provide evidence for PRMT7’s function in regulating AMYFs proliferation and differentiation during lung alveologenesis. In PRMT7-deficient mice, we found reduced AMYFs proliferation and differentiation, abnormal elastin deposition, and failure of alveolar septum formation. We further shown that oncogene forkhead box M1 (Foxm1) is a direct target of PRMT7 and that PRMT7-catalyzed monomethylation at histone H4 arginine 3 (H4R3me1) directly associate with chromatin of Foxm1 to activate its transcription, and thereby regulate of cell cycle-related genes to inhibit AMYFs proliferation and differentiation. Overexpression of Foxm1 in isolated myofibroblasts (MYFs) significantly rescued PRMT7-deficiency-induced cell proliferation and differentiation defects. Thus, our results reveal a novel epigenetic mechanism through which PRMT7-mediated histone arginine monomethylation activates Foxm1 transcriptional expression to regulate AMYFs proliferation and differentiation during lung alveologenesis and may represent a potential target for intervention in pulmonary diseases.

Amyloid aggregation and microbial infection are considered as pathological risk factors for developing amyloid diseases, including Alzheimer's disease (AD), type II diabetes (T2D), Parkinson's disease (PD), and medullary thyroid carcinoma (MTC). Due to the multifactorial nature of amyloid diseases, single-target drugs and treatments have mostly failed to inhibit amyloid aggregation and microbial infection simultaneously, thus leading to marginal benefits for amyloid inhibition and medical treatments. Herein, we proposed and demonstrated a new “anti-amyloid and antimicrobial hypothesis” to discover two host-defense antimicrobial peptides of α-defensins containing β-rich structures (human neutrophil peptide of HNP-1 and rabbit neutrophil peptide of NP-3A), which have demonstrated multi-target, sequence-independent functions to (i) prevent the aggregation and misfolding of different amyloid proteins of amyloid-β (Aβ, associated with AD), human islet amyloid polypeptide (hIAPP, associated with T2D), and human calcitonin (hCT, associated with MTC) at sub-stoichiometric concentrations, (ii) reduce amyloid-induced cell toxicity, and (iii) retain their original antimicrobial activity upon the formation of complexes with amyloid peptides. Further structural analysis showed that the sequence-independent amyloid inhibition function of α-defensins mainly stems from their cross-interactions with amyloid proteins via β-structure interactions. The discovery of antimicrobial peptides containing β-structures to inhibit both microbial infection and amyloid aggregation greatly expands the new therapeutic potential of antimicrobial peptides as multi-target amyloid inhibitors for better understanding pathological causes and treatments of amyloid diseases., We report a new “anti-amyloid and antimicrobial hypothesis” by discovering host-defense antimicrobial peptides of α-defensins containing β-sheet structures, which possess inhibition functions against amyloid aggregation and microbial infection.

Background: Effective cancer immunotherapy is significantly affected by intratumoral heterogeneity, not only in different cell types and functions but also in the spatial pattern of immune cells within the tumor tissue. While most single-cell RNA sequencing technologies could enable the exploration of gene expression heterogeneity at the single-cell level, they cannot reveal spatial information within the tumor for us to map the whole transcriptome with morphological context. Spatial transcriptomics is an in situ capturing technique, which profiles gene expression at the RNA level, whilst preserving the spatial information of histological tissue sections. Thus we try to develop our spatial transcriptomics assay through a serial of validation experiments and to explore the mechanism of immune therapy against tumors. Material and Method: Firstly, the tumor was frozen and sections were cryosectioned at 10 μm thickness. Sections processing including H&E staining, tissue optimization, permeabilization, reverse transcription, and cDNA library preparation was carried out following the user guide of Visium Spatial Gene Expression Reagent Kits (10X Genomics). And the final cDNA libraries were sequenced using the Illumina Novaseq instrument. Using gene expression matrix and aligned H&E image processed by Cell Ranger and Loupe Browser with default parameters, we performed data QC, normalization, dimensionality reduction, and clustering by Seurat and cell components identification in tumor microenvironment based on a multistep approach. Differential gene expression and spatial heterogeneity were analyzed in each cluster. Results: Here we established a reliable system for spatial transcriptomics assay to elucidate the mechanism of anti-PD1 treatment in MC38 syngeneic colorectal tumor. Using this system, we constructed the gene expression spatial patterns of tumor cells and immune cells, including periphery and center of tumor cell, immune-cell enrichment area, and tumor cell surrounding the immune cell. Furthermore, we explored the cell-cell interactions in which the tumor cells directly interact with adjacent non-tumor cells, for example, macrophages. Using this system, we tried to investigate the mechanism of anti-PD-1 therapy against the tumors by comparing the spatial transcriptome profiles after the treatment with anti-PD-1 or isotype control in colorectal cancer models. Interestingly, changes in both gene-level and spatial levels were observed, and it will help reveal how the immune therapy may shake up the complex ecosystem. Summary: We established a reliable system for spatial transcriptomics analysis and explored the mechanism of anti-PD-1 treatment against the colorectal cancer by using this system. Citation Format: Panpan Wang, Huacheng He, Qiyao Zhang, Jingjing Wang, Dan Lu, Fei Duan, Qiangqiang Fan, Qingyang Gu, Qunsheng Ji. Establishment of spatial transcriptomics assay to study the mechanism of immune therapy against tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6128.

The thrust allocation of Dynamic Positioning System (DPS) equipped with multiple thrusters is usually formulated as an optimization problem. Hydrodynamic interaction effects such as thruster-thruster interaction results in thrust loss. This interaction is generally avoided by defining forbidden zones for some azimuth angles. However, it leads to a higher power consumption and stuck thrust angles. For the purpose of improving the traditional Forbidden Zone (FZ) method, this paper proposes an optimized thrust allocation algorithm based on Radial Basis Function (RBF) neural network and Sequential Quadratic Programming (SQP) algorithm, named RBF-SQP. The thrust coefficient is introduced to express the thrust loss which is then incorporated into the mathematical model to remove forbidden zones. Specifically, the RBF neural network is constructed to approximate the thrust efficiency function, and the SQP algorithm is selected to solve the nonlinear optimization problem. The training dataset of RBF neural network is obtained from the model test of thrust-thrust interaction. Numerical simulations for the dynamic positioning of a semi-submersible platform are conducted under typical operating conditions. The simulation results demonstrate that the demanded forces can be correctly distributed among available thrusters. Compared with the traditional methods, the proposed thrust allocation algorithm can achieve a lower power consumption. Moreover, the advantages of considering hydrodynamic interaction effects and utilizing a neural network for function fitting are also highlighted, indicating a practical application prospect of the optimized algorithm.

The obstacle avoidance problem of autonomous surface vessels (ASV) has attracted the attention of the marine control research community for long years. Out of safety consideration, it is important for ASV to avoid all kinds of obstacles like shores, cliffs, floaters and other vessels. Developing a heading and path planning strategy for ASV is the main task and the remaining challenge. Traditional obstacle avoidance algorithms lead to too much computing in working environment. The issue of computation cost can be solved by training obstacle avoidance models with reinforcement learning (RL). By using the RL method, the ASV will choose the most efficient action according to the ASV’s experience it learned from the past. In this paper, RL is adopted to design a decision-making agent for obstacle avoidance. To train the obstacle avoidance model under a sparse feedback environment, hierarchical reinforcement learning (HRL) method is applied. Using this algorithm, better obstacle avoidance performance and longer survival time can be achieved. Memory pool modification and target network modification are also used to smooth the training process of the ASV. Simulation results demonstrate that HRL can make the learning process of un-manned ship’s obstacle avoidance smoother and more effective. Also, the living time of ASVs is improved.

Zwitterionic hydrogels, as highly hydrated and soft materials, have been considered as promising materials for wound dressing, due to their unique antifouling and mechanical properties. While the viscoelasticity and softness of zwitterionic hydrogels are hypothetically essential for creating adaptive cellular niches, the underlying mechanically regulated wound healing mechanism still remains elusive. To test this hypothesis, we fabricated zwitterionic poly(sulfobetaine methacrylate) (polySBMA) hydrogels with different elastic moduli prepared at different crosslinker contents, and then applied the hydrogels to full-thickness cutaneous wounds in mice. In vivo wound healing studies compared the mechanical cue-induced effects of soft and stiff polySBMA hydrogels on wound closure rates, granulation tissue formation and collagen deposition. Collective results showed that the softer and more viscoelastic hydrogels facilitated cell proliferation, granulation formation, collagen aggregation, and chondrogenic ECM deposition. Such high wound healing efficiency by the softer hydrogels is likely attributed to stress dissipation by expanding the cell proliferation, the up-regulation of blood vessel formation, and the enhanced polarization of M2/M1 macrophages, both of which would provide more oxygen and nutrients for cell proliferation and migration, leading to enhanced wound repair. This work not only reveals a mechanical property–wound healing relationship of zwitterionic polySBMA hydrogels, but also provides a promising candidate and strategy for the next-generation of wound dressings.

Intervertebral disc degeneration (IDD) usually causes lower back and neck pain with a high incidence, which significantly reduces the life quality of patients. However, there is no effective treatment available currently. Our previous study has found that hydrogen sulfide (H2S) shows potential therapeutic effect toward IDD. However, the burst release and fast vanishing of H2S in the lesion severely limit its further application. Therefore, in this study, we develop a pH and enzyme dual-responsive H2S releasing hydrogel system to treat IDD. This hydrogel named Col-JK1 is quite stable under neutral conditions but rapidly releases H2S by responding to acidic pH and high matrix metalloproteinases (MMPs) levels in the pathological IDD environment. In vivo study firstly uncovered that Col-JK1 can effectively impede disc degeneration in a puncture-induced IDD rat model. Further in vitro studies reveal that Col-JK1 protects the disc from degeneration by inhibiting the apoptosis of nucleus pulposus (NP) cells and attenuating the degradation of the disc extracellular matrix (ECM). And the protective effect of Col-JK1 is attributed to its anti-inflammatory effects through the regulation of the NF-κB signaling pathway. Thus, our study provides a novel therapeutic option for IDD therapy by controlling the release of H2S.

A review of the synthesis, structure and specifically the effect of counter-ions on the properties of ionic metal organic frameworks (ionic-MOFs) is presented, highlighting the important advances in this regard over the past decade. Most focus is on ionic porous metal–organic frameworks (MOFs) materials consisting of porous anionic or cationic frameworks and cationic or anionic guests. The structure and performance of cationic and anionic MOFs are influenced by several factors, such as organic ligands, metal ions and charge-balancing anions. These types of anionic and cationic materials have distinct advantages in comparison with neutral MOFs in the design of functional materials and their synthesis affords several distinct advantages over that for routine neutral frameworks by virtue of the isolated charged species in confined nano-spaces. The nanosized and charged pores in these ionic structures generate a strong interaction between the host and guest molecules, including enhanced adsorption towards small gases and solvent molecules. Ionic-MOFs can be easily modified via ion exchange and accommodate other charged guest molecules, making them an ideal platform for different applications, such as functional materials. The development of synthesis methods by ion exchange and the potential applications of such cationic or anionic structures have been discussed thoroughly in this review.

Zwitterionic hydrogels are promising biomaterials because of their high water content, three-dimensional network structure, and antifouling property. However, it still remains unclear about how mechanical properties of zwitterionic hydrogels affect their antifouling property. In this work, we propose a simple, thermal-pretreatment method to fabricate poly(sulfobetaine methacrylate) (pSBMA) hydrogels with varied mechanical properties that can be readily tuned by thermal pretreatment time and cross-linker density, as well as to correlate their mechanical property with antifouling property. The resulting thermal-treated pSBMA hydrogels show significantly enhanced mechanical properties with tunable compressive modulus and elastic modulus as compared to the untreated hydrogels. A combination of ELISA investigations and short-term cell adhesion assays also confirm that pSBMA hydrogels exhibit superior antifouling properties to resist protein adsorption and cell adhesion. Further analysis shows a linear inversion correlation between elastic modulus and protein adsorption of pSBMA hydrogels, i.e., the hydrogel with the higher elastic modulus exhibits the lower protein adsorption (the better antifouling property). This work not only provides a simple thermal-pretreatment strategy for fabricating pSBMA hydrogels, but also demonstrates multifunctional properties of the pSBMA hydrogels, which possess a great potential to fulfill some biomedical applications.

Skin wound healing is a still long-history challenging problem and impeded by the foreign-body reaction including severe inflammation response, poor neovascularization, incomplete re-epithelialization and defective ECM remodeling. Development of biocompatible polymers, in combination with specific drugs or growth factors, has been considered as a promising strategy to treat skin wounds. Significant research efforts have been made to develop poly(ethylene glycol) PEG-based polymers for wound healing, however less efforts has been paid to zwitterionic materials, some of which have demonstrated their super low-fouling property in vitro and anti-inflammatory property in vivo. Here, we synthesized ultra-low-fouling zwitterionic sulfated poly(sulfobetaine methacrylate) (polySBMA) hydrogels and applied them to full-thickness cutaneous wounds in mice. The healing effects of SBMA hydrogels on the wound closure, re-epithelialization ratio, ECM remodeling, angiogenesis, and macrophage responses during wound healing processes were histologically evaluated by in vivo experiments. Collective results indicate that SBMA hydrogels promote full-thickness excisional acute wound regeneration in mice by enhancing angiogenesis, decreasing inflammation response, and modulating macrophage polarization. Consistently, the incorporation of SBMA into PEG hydrogels also improved the overall wound healing efficiency as compared to pure PEG hydrogels. This work demonstrates zwitterionic SBMA hydrogels as promising wound dressings for treating full-thickness excisional skin wounds. Statement of Significance Development of highly effective wound regeneration system is practically important for biomedical applications. Here, we synthesized ultra-low-fouling zwitterionic sulfated poly(sulfobetaine methacrylate) (polySBMA) hydrogels and applied it to full-thickness cutaneous wounds in mice, in comparison with PEG hydrogels as a control. We are the first to examine and reveal the difference between zwitterionic SBMA hydrogels and PEG hydrogels using a full-thickness excisional mice model. Overall, a series of in vivo systematic tests demonstrated that zwitterionic SBMA hydrogels exhibited superior wound healing property in almost all aspects as compared to PEG hydrogels.

Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia after injury. Hemisection spinal cord injury (HSCI) is a special type of SCI. The most important difference between HSCI and SCI is the occurrence of spinal cord dissection. Therefore, a calcium alginate hydrogel combined with dental pulp stem cells (DPSCs) and fibroblast growth factor 21 (FGF21) was designed based on the principle that cadherin expression is regulated by calcium ion concentration. Each element in Ca2+@Alg-FGF21 + DPSC hydrogel can exert different effects 1). calcium ions can regulate cadherin to achieve self-adhesion; 2). alginic acid can absorb calcium ions to prevent calcium overload induced injury; 3) FGF21 can regulate microenvironment; 4). DPSCs can supplement exogenous neurons. The multi-factorially comprehensive effects were hypothesized to improve the HSCI recovery. It was revealed in our study that Ca2+@Alg-FGF21 + DPSC hydrogel could effectively promote the recovery after spinal cord hemisection in mice via regulating apoptosis and autophagy, providing potential clues and cues of using Ca2+@Alg-FGF21 + DPSC hydrogel for HSCI treatment.

This paper presents a Predicted Trajectory Approach (PTA) for global motion planning of an underactuated unmanned surface vehicle (USV). Different from the conventional path planning algorithms which mostly focus on the shortest, safest or smoothest paths, PTA takes all the dynamic constraints of the USV into account, and finds the global trajectory that can be traced precisely via its own maneuvering system. In present strategy, the predicted trajectories produced by the mathematical model of the USV are decomposed into a series of waypoints on grid map. Then an efficient trajectory can be found for the USV by performing the A* search method. To improve the search efficiency and accuracy, the PTA is enhanced with global path guiding (GPTA). When searching for feasible trajectories, GPTA can employ the global path obtained by Theta* to accurately estimate the heuristic cost of the objective function, rather than using the Euclidean distance directly as PTA does. Numerical simulations in various scenarios are conducted to compare the performance of the PTA, GPTA, Trajectory Units (TUs) and hybrid path planning algorithm combining global and local path planning (HGL). The results demonstrate that GPTA has higher safety and navigation efficiency for motion planning of the underactuated USV.

This paper presents Extended Dynamic Window Approach (EDWA) for the automatic berthing of an underactuated unmanned surface vehicle (USV). Different from the conventional works based on Control Theory, present approach focuses on the field of planning to complete the process of the automatic berthing. The approach takes all the dynamic constraints of the USV into account, and obtains the whole predicted trajectories of both constant force and deceleration phases. By performing the collision detection, the predicted trajectories with obstacles are discarded and remaining trajectories are evaluated by an objective function to select the optimal trajectory for the USV. The case studies are conducted in order to verify the feasibility and performance of the presented approach. The results show that the approach can realize the automatic berthing under the influence of wind loads and obstacles.

Most photothermal converting systems are not biodegradable, which bring the uneasiness when they are administered into human body due to the uncertainty of their fate. Hereby, we developed a mussel-inspired PLGA/polydopamine core-shell nanoparticle for cancer photothermal and chemotherapy. With the help of an anti-EGFR antibody, the nanoparticle could effectively enter head and neck cancer cells and convert near-infrared light to heat to trigger drug release from PLGA core for chemotherapy as well as ablate tumors by the elevated temperature. Due to the unique nanoparticle concentration dependent peak working-temperature nature, an overheating or overburn situation can be easily prevented. Since the nanoparticle was retained in the tumor tissue and subsequently released its payload inside the cancer cells, no any doxorubicin-associated side effects were detected. Thus, the developed mussel-inspired PLGA/polydopamine core-shell nanoparticle could be a safe and effective tool for the treatment of head and neck cancer.The described EGFR targeted PLGA/polydopamine core-shell nanoparticle (PLGA/PD NP) is novel in the following aspects: Different from most photothermal converting nanomaterials, PLGA/PD NP is biodegradable, which eliminates the long-term safety concerns thwarting the clinical application of photothermal therapy. Different from most photothermal nanomaterials, upon NIR irradiation, PLGA/PD NP quickly heats its surrounding environment to a NP concentration dependent peak working temperature and uniquely keeps that temperature constant through the duration of light irradiation. Due to this unique property an overheating or overburn situation for the adjacent healthy tissue can be easily avoided. The PLGA/PD NP releases its payload through detaching PD shell under NIR laser irradiation. The EGFR-targeted doxorubicin-loaded PLGA/PD NP effectively eradicate head and neck tumor in vivo through the synergism of photothermal therapy and chemotherapy while not introducing doxorubicin associated cardiotoxicity.

Conventional 2-hydroxyethyl methacrylate (HEMA)-based hydrogels have an inverse relationship between optical transparency (OP) and oxygen permeability (Dk) as a function of water content. While the higher water content favors the oxygen permeability of HEMA-based hydrogels, it also causes poor optical transparency due to the water-induced scattering center effect. Here, we propose and demonstrate that the incorporation of zwitterionic [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide (SBMA) with HEMA hydrogels enables the achievement of both properties (OP = 98% and Dk = 54.7) in hydrogels at high water contents of 84%, and both values are much higher than those of pure HEMA hydrogels (OP = 2.3% and Dk = 17.5 barriers). HEMA-SBMA hydrogels are crosslinked by electrostatic interactions between the zwitterionic SBMA groups and hydrogen bonds between the HEMA groups. The introduction of SBMA into HEMA not only increases the quantity and quality of strongly binding water inside the networks, but also affects the porous structure of the gels, both of which are correlated with OP and Dk. Moreover, hybrid HEMA-SBMA hydrogels demonstrate their excellent antifouling function to prevent nonspecific protein adsorption in vitro, as well as their biocompatibility and hemocompatibility when implanted in mice in vivo. A combination of these excellent properties of HEMA-SBMA hydrogels (high water content, high optical transparency, high oxygen permeability, good antifouling function, and low foreign-body reaction) makes them highly promising for contact lens-based ophthalmic applications. This work, in line with our other HEMA-CBMA hydrogels, offers a new strategy to design hybrid hydrophilic-zwitterionic materials for improving their multi-faceted properties of interest, beyond the conventional designs of hydrophilic-hydrophilic and hydrophilic-hydrophobic materials.

Photodynamic therapy has attracted significant attention due to its localized treatment advantage. However, the non-specific distribution of photosensitizers and the subsequent potential toxicity caused by sunshine exposure hinder its wide adoption in cancer treatment. To minimize these unwanted effects and improve its efficacy, we developed a bioactivatable self-quenched nanogel, which remains in its inactive state in healthy tissues. Anti-EGFR Affibody decorated nanogels can effectively target head and neck cancer and release activated pheophorbide A in a reducing environment, such as in the tumor stroma and cytoplasm. Consequently, the EGFR targeted nanogel coupled with NIR irradiation alleviates tumor burden by 94.5% while not inducing systemic toxicity.

The extracellular matrix (ECM) plays the role of a double-edged sword for controlling the differentiation of fibroblasts toward contractile myofibroblasts in the wound healing process. However, the exact structure-function relationship between ECM morphology and fibroblast behaviors still remains unclear. To better understand this relationship, herein, we designed and prepared a series of biocompatible polycaprolactone (PCL)-based fibers with different fiber diameters (nano vs micro) and different alignments (random vs aligned) using a simple electrospinning process, with a particular attention to the morphological effect of PCL fiber scaffolds on guiding fibroblast behaviors. Microfibers with the larger fiber diameters induce less cell spreading, adhesion, differentiation, and migration because of their lower surface tension. In contrast, nanofibers will retain fibroblast cells with typical spindle shapes and promote the expression of focal adhesion proteins through the integrin pathway. Furthermore, nanofibers upregulate the expression of α-smooth muscle actin (α-SMA), transforming growth factor, and vimentin filaments, indicating that the size change of the PCL fiber matrix from micrometers to nanometers indeed alters fibroblast differentiation to activate more α-SMA-expressed contractile myofibroblasts. Such a fiber size-dependent fibroblast behavior is largely attributed to the enhanced surface tension from the dressing matrix, which helps to promote the conversion of fibroblasts to myofibroblasts via either tissue regeneration or fibrosis. Therefore, this work further indicated that the rearrangement of collagen from nano-tropocollagen to micro-collagen bundles during the wound healing process can reverse fibroblasts to myofibroblasts from motivated to demise. This finding allows us to achieve the structural-based design of a new fibrous matrix for promoting wound healing and tissue regeneration.

Hydrogen sulfide (H

Herein, we discovered that the sunflower sporopollenin exine capsule (SEC) is an effective photothermal agent. In vitro study finds that the spikes on the surface of the sunflower SEC and its structural integrity are the two key factors to determine the photothermal effect. In vivo melanoma mouse model proves that the sunflower SEC can effectively inhibit tumor growth by inducing cell apoptosis and reducing cell proliferation through the near-infra red light triggered photothermal therapy. The in vivo biosafety of the SEC is also validated. In consideration of its safety, uniform size distribution and abundant availability, the sunflower SEC will be a promising photothermal agent candidate for clinical translational application.

Chemotherapy has been adopted for cancer treatment for decades. However, its efficacy and safety are frequently compromised by the multidrug-resistance of cancer cells and the poor cancer cell selectivity of anticancer drugs. Hereby, we report a combination of a pyridine-2-thiol containing polymer and copper which can effectively kill a wide spectrum of cancer cells, including drug resistant cancer cells, while sparing normal cells. The polymer nanoparticle enters cells via an exofacial thiol facilitated route, and releases active pyridine-2-thiol with the help of intracellularly elevated glutathione (GSH). Due to their high GSH level, cancer cells are more vulnerable to the polymer/copper combination. In addition, RNA microarray analysis revealed that the treatment can reverse cancer cells' upregulated oncogenes (CIRBP and STMN1) and downregulated tumor suppressor genes (CDKN1C and GADD45B) to further enhance the selectivity for cancer cells.

Imbalance of metal ions in the wound microenvironment is a key factor that leads to delayed wound healing. However, single metal administration to enhance wound repair is usually not enough due to the overlapping nature of the wound healing phases. Herein, a facile freeze-thawing strategy is developed to incorporate chitosan/ions hydrogel into medical gauzes to realize on-demand release of multiple ions to accelerate wound healing. In vitro study reveals that the gauzes can temporally release multiple metal ions on demand, and the released metal ions show effectiveness in killing bacteria and expediting cell migration. In vivo studies demonstrate that the metal ions loaded gauzes can efficiently enhance infected wound healing. Further histological analysis find that these metal ion-loaded gauzes accelerate wound healing by promoting granulation formation, collagen deposition and maturation, re-epithelization, angiogenesis, and inhibiting inflammation via regulating the expression of inflammatory factors (e.g., tumor necrosis factor-α) and polarization of macrophages. Thus, this novel metal ions delivery system has great potential in infected tissue repair and antibacterial applications.

Gauze is the leading dressing for wound management. However, infection and tissue adhesion pose serious challenges to the application of gauzes. Herein, inspired by the self-cleaning property of lotus leaf, we develop a novel antiadhesive and antibacterial gauze. The gauze, named Lotus@Gauze, is fabricated by decorating an ordinary medical gauze sequentially with polydopamine, perfluorocarbon and silver nanoparticle to obtain a lotus leaf-mimic surface structure. Lotus@Gauze exhibits excellent antiadhesive and antibacterial effects, and its antibacterial ability is enhanced under NIR irradiation due to the photothermal effect of polydopamine. Furthermore, in vivo results reveal that, in comparison with clinically available antiadhesive or antibacterial gauzes, Lotus@Gauze shows better efficacy in promoting infectious wound regeneration due to its low tissue adhesion and effective bactericidal activity. Overall, this study explores a new attempt to overcome the challenge of tissue adhesion and infection by integrating antiadhesive and antibacterial properties into one piece of simple gauze.

Skin wounds, especially chronic wounds such as pressure and diabetic ulcers, are posing a huge threat to healthcare systems worldwide. Thus, novel strategies to realize effective wound therapy are nowadays extremely needed. Herein, we are the first to report a combination therapy of electric stimulation and heat for wound healing just using a facile piezoelectric and photothermal dual functional film. The film, name as CM@DA, is simply fabricated by coating polydopamine on a chitosan film. CM@DA generates electric voltages under mechanical pressure and shows photothermal effect with irradiation of near-infra red (NIR) light. In vivo experiment with rat full-thickness wound model validates that CM@DA with NIR can effectively promote wound regeneration due to the generation of electric stimulation and heat on wounds. The healing mechanism of CM@DA is further investigated, and the result demonstrates that CM@DA enhances wound healing through a pathway in which heat shock protein 90 (Hsp90) and hypoxia-inducible factor 1α (HIF-1α) participate. These results indicate that CM@DA is a promising wound dressing candidate for clinical application in the future.