Advances in Polysaccharides for Cartilage Tissue Engineering Repair: A Review.

Cartilage repair has been a significant challenge in orthopedics that has not yet been fully resolved. Due to the absence of blood vessels and the almost cell-free nature of mature cartilage tissue, the limited ability to repair cartilage has resulted in significant socioeconomic pressures. Polysaccharide materials have recently been widely used for cartilage tissue repair due to their excellent cell loading, biocompatibility, and chemical modifiability. They also provide a suitable microenvironment for cartilage repair and regeneration. In this Review, we summarize the techniques used clinically for cartilage repair, focusing on polysaccharides, polysaccharides for cartilage repair, and the differences between these and other materials. In addition, we summarize the techniques of tissue engineering strategies for cartilage repair and provide an outlook on developing next-generation cartilage repair and regeneration materials from polysaccharides. This Review will provide theoretical guidance for developing polysaccharide-based cartilage repair and regeneration materials with clinical applications for cartilage tissue repair and regeneration.

Hydrophobic Cross-Linked Chains Regulate High Wet Tissue Adhesion Hydrogel with Toughness, Anti-hydration for Dynamic Tissue Repair.

Hydrogel adhesion materials are widely reported for tissue engineering repair applications, however, wet tissue surface moisture can reduce the wet-adhesion properties and mechanical strength of hydrogels limiting their application. Here, anti-hydration gelatin-acrylic acid-ethylene dimethacrylate (GAE) hydrogels with hydrophobic cross-linked chains are constructed. The prepared GAE hydrogel is soaked in PBS (3 days) with a volume change of 0.6 times of the original and the adhesive strength, Young's modulus, toughness, and burst pressure are maintained by ≈70% of the original. A simple and universal method is used to introduce hydrophobic chains as cross-linking points to prepare hydrogels with anti-hydration, toughness, and high wet state adhesion. The hydrophobic cross-linked chains not only restrict the movement of molecular chains but also hinder the intrusion of water molecules. Antihydration GAE hydrogels exhibit good biocompatibility, slow drug release, and dynamic oral wet-state tissue repair properties. Therefore, the anti-hydration hydrogel has excellent toughness, wet tissue adhesion properties, and good prospects for biological applications.

Multifunctional wet-adhesive chitosan/acrylic conduit for sutureless repair of peripheral nerve injuries.

The incidence of peripheral nerve injury (PNI) is high worldwide, and a poor prognosis is common. Surgical closure and repair of the affected area are crucial to ensure the effective treatment of peripheral nerve injuries. Despite being the standard treatment approach, reliance on sutures to seal the severed nerve ends introduces several limitations and restrictions. This technique is intricate and time-consuming, and the application of threading and punctate sutures may lead to tissue damage and heightened tension concentrations, thus increasing the risk of fixation failure and local inflammation. This study aimed to develop easily implantable chitosan-based peripheral nerve repair conduits that combine acrylic acid and cleavable N-hydroxysuccinimide to reduce nerve damage during repair. In ex vivo tissue adhesion tests, the conduit achieved maximal interfacial toughness of 705 J m-2 ± 30 J m-2, allowing continuous bridging of the severed nerve ends. Adhesive repair significantly reduces local inflammation caused by conventional sutures, and the positive charge of chitosan disrupts the bacterial cell wall and reduces implant-related infections. This promises to open new avenues for sutureless nerve repair and reliable medical implants.

Prospects of Using Chitosan-Based Biopolymers in the Treatment of Peripheral Nerve Injuries.

Peripheral nerve injuries are common neurological disorders, and the available treatment options, such as conservative management and surgical repair, often yield limited results. However, there is growing interest in the potential of using chitosan-based biopolymers as a novel therapeutic approach to treating these injuries. Chitosan-based biopolymers possess unique characteristics, including biocompatibility, biodegradability, and the ability to stimulate cell proliferation, making them highly suitable for repairing nerve defects and promoting nerve regeneration and functional recovery. Furthermore, these biopolymers can be utilized in drug delivery systems to control the release of therapeutic agents and facilitate the growth of nerve cells. This comprehensive review focuses on the latest advancements in utilizing chitosan-based biopolymers for peripheral nerve regeneration. By harnessing the potential of chitosan-based biopolymers, we can pave the way for innovative treatment strategies that significantly improve the outcomes of peripheral nerve injury repair, offering renewed hope and better prospects for patients in need.

Micron track chitosan conduit fabricated by 3D-printed model topography provides bionic microenvironment for peripheral nerve regeneration.

The micron track conduit (MTC) and nerve factor provide a physical and biological model for simulating peripheral nerve growth and have potential applications for nerve injury. However, it has rarely been reported that they synergize on peripheral nerves. In this study, we used bioderived chitosan as a substrate to design and construct a neural repair conduit with micron track topography using threedimensional (3D) printing topography. We loaded the MTC with neurotrophin-3 (NT-3) to promote the regeneration of sensory and sympathetic neurons in the peripheral nervous system. We found that the MTC@NT3 composite nerve conduit mimicked the microenvironment of peripheral nerves and promoted axonal regeneration while inducing the targeted growth of Schwann cells, which would promote functional recovery in rats with peripheral nerve injury. Artificial nerve implants with functional properties can be developed using the strategy presented in this study.

Mimosa-Inspired Stimuli-Responsive Curling Bioadhesive Tape Promotes Peripheral Nerve Regeneration.

Trauma often results in peripheral nerve injuries (PNIs). These injuries are particularly challenging therapeutically because of variable nerve diameters, slow axonal regeneration, infection of severed ends, fragility of the nerve tissue, and the intricacy of surgical intervention. Surgical suturing is likely to cause additional damage to peripheral nerves. Therefore, an ideal nerve scaffold should possess good biocompatibility, diameter adaptability, and a stable biological interface for seamless biointegration with tissues. Inspired by the curl of Mimosa pudica, this study aimed to design and develop a diameter-adaptable, suture-free, stimulated curling bioadhesive tape (SCT) hydrogel for repairing PNI. The hydrogel is fabricated from chitosan and acrylic acid-N-hydroxysuccinimide lipid via gradient crosslinking using glutaraldehyde. It closely matches the nerves of different individuals and regions, thereby providing a bionic scaffold for axonal regeneration. In addition, this hydrogel rapidly absorbs tissue fluid from the nerve surface achieving durable wet-interface adhesion. Furthermore, the chitosan-based SCT hydrogel loaded with insulin-like growth factor-I effectively promotes peripheral nerve regeneration with excellent bioactivity. This procedure for peripheral nerve injury repair using the SCT hydrogel is simple and reduces the difficulty and duration of surgery, thereby advancing adaptive biointerfaces and reliable materials for nerve repair.

Leaf-stomata-inspired packaging nanofibers with humidity-triggered thymol release based on thymol/EVOH coaxial electrospinning.

Active packaging systems that are sustainable and capable of delivering antimicrobial agents intelligently are in demand in food industry. In this work, an extremely simple strategy inspired by leaf stomata was introduced to smartly trigger thymol release at different relative humidity using EVOH as the "stomata". Thymol was encapsulated into ethylene vinyl alcohol copolymer (EVOH) to form core-shell nanofibers (thymol/EVOH) via coaxial electrospinning. The core-shell structure of the nanofiber was confirmed by transmission electron microscopy. Thymol release could be triggered by the relative humidity (RH), and nanofibers released more thymol at 90% RH than at 30% RH. In addition, this functionalized nanofibers showed excellent antibacterial activity in vitro against Escherichia coli and Staphylococcus aureus and performed good biocompatibility. The nanofiber film was also applied to fruit preservation, and was found to extend the strawberries shelf-life. Sensory analysis also showed that the strawberries flavor treated by thymol/EVOH nanofibers presented high acceptability. The work will provide an innovative approach to design packaging film.

Janus mucosal dressing with a tough and adhesive hydrogel based on synergistic effects of gelatin, polydopamine, and nano-clay.

There are many problems and challenges related to the treatment of highly prevalent oral mucosal diseases and oral drug delivery because of a large amount of saliva present in the oral cavity, the accompanying oral movements, and unconscious swallowing in the mouth. Therefore, an ideal oral dressing should possess stable adhesion and superior tough strength in the oral cavity. However, this fundamental requirement greatly limits the use of synthetic adhesive dressings for oral dressings. Here, we developed a mussel-inspired Janus gelatin-polydopamine-nano-clay (GPC) hydrogel with controlled adhesion and toughness through the synergistic physical and chemical interaction of gelatin (Gel), nano-clay, and dopamine (DA). The hydrogel not only exhibits strong wet adhesion force (63 kPa) but also has high toughness (1026 ± 100 J m-3). Interfacial adhesion of hydrogels is achieved by modulating the interaction of catechol groups of the hydrogel with specific functional groups (e.g., NH2, SH, OH, and COOH) on the tissue surface. The matrix dissipation of the hydrogel is regulated by physical crosslinking of gelatin, chemical crosslinking of gelatin with polydopamine (Michael addition and Schiff base formation), and nano-clay-induced constraint of the molecular chain. In addition, the GPC hydrogel shows high cell affinity and favors cell adhesion and proliferation. The hydrogel's instant and strong mucoadhesive properties provide a long-lasting therapeutic effect of the drug, thereby enhancing the healing of oral ulcers. Therefore, mussel-inspired wet-adhesion Janus GPC hydrogels can be used as a platform for mucosal dressing and drug delivery systems. STATEMENT OF SIGNIFICANCE: It is a great challenge to treat oral mucosal diseases due to the large amount of saliva present in the oral cavity, the accompanying oral movements, unconscious swallowing, and flushing of drugs in the mouth. To overcome the significant limitations of clinical bioadhesives, such as weakness, toxicity, and poor usage, in the present study, we developed a simple method through the synergistic effects of gelatin, polydopamine, and nano-clay to prepare an optimal mucosal dressing (Janus GPC) that integrates Janus, adhesion, toughness, and drug release property. It fits effectively in the mouth, resists saliva flushing and oral movements, provides oral drug delivery, and reduces patient discomfort. The Janus GPC adhesive hydrogels have great commercial potential to support further the development of innovative therapies for oral mucosal diseases.

Application of Chitosan and Its Derivative Polymers in Clinical Medicine and Agriculture.

Chitosan is a biodegradable natural polymer derived from the exoskeleton of crustaceans. Because of its biocompatibility and non-biotoxicity, chitosan is widely used in the fields of medicine and agriculture. With the latest technology and technological progress, different active functional groups can be connected by modification, surface modification, or other configurations with various physical, chemical, and biological properties. These changes can significantly expand the application range and efficacy of chitosan polymers. This paper reviews the different uses of chitosan, such as catheter bridging to repair nerve broken ends, making wound auxiliaries, as tissue engineering repair materials for bone or cartilage, or as carriers for a variety of drugs to expand the volume or slow-release and even show potential in the fight against COVID-19. In addition, it is also discussed that chitosan in agriculture can improve the growth of crops and can be used as an antioxidant coating because its natural antibacterial properties are used alone or in conjunction with a variety of endophytic bacteria and metal ions. Generally speaking, chitosan is a kind of polymer material with excellent development prospects in medicine and agriculture.

Recent Progress in Intelligent Wearable Sensors for Health Monitoring and Wound Healing Based on Biofluids.

The intelligent wearable sensors promote the transformation of the health care from a traditional hospital-centered model to a personal portable device-centered model. There is an urgent need of real-time, multi-functional, and personalized monitoring of various biochemical target substances and signals based on the intelligent wearable sensors for health monitoring, especially wound healing. Under this background, this review article first reviews the outstanding progress in the development of intelligent, wearable sensors designed for continuous, real-time analysis, and monitoring of sweat, blood, interstitial fluid, tears, wound fluid, etc. Second, this paper reports the advanced status of intelligent wound monitoring sensors designed for wound diagnosis and treatment. The paper highlights some smart sensors to monitor target analytes in various wounds. Finally, this paper makes conservative recommendations regarding future development of intelligent wearable sensors.

Design and Performance Verification of a Space Radiation Detection Sensor Based on Graphene.

In order to verify the performance of a graphene-based space radiation detection sensor, the radiation detection principle based on two-dimensional graphene material was analyzed according to the band structure and electric field effect of graphene. The method of space radiation detection based on graphene was studied and then a new type of space radiation sensor samples with small volume, high resolution, and radiation-resistance was formed. Using protons and electrons, the electrical performance of GFET radiation sensor was verified. The designed graphene space radiation detection sensor is expected to be applied in the radiation environment monitoring of the space station and the moon, and can also achieve technological breakthroughs in pulsar navigation and other fields.

Repair of Peripheral Nerve Injury Using Hydrogels Based on Self-Assembled Peptides.

Peripheral nerve injury often occurs in young adults and is characterized by complex regeneration mechanisms, poor prognosis, and slow recovery, which not only creates psychological obstacles for the patients but also causes a significant burden on society, making it a fundamental problem in clinical medicine. Various steps are needed to promote regeneration of the peripheral nerve. As a bioremediation material, self-assembled peptide (SAP) hydrogels have attracted international attention. They can not only be designed with different characteristics but also be applied in the repair of peripheral nerve injury by promoting cell proliferation or drug-loaded sustained release. SAP hydrogels are widely used in tissue engineering and have become the focus of research. They have extensive application prospects and are of great potential biological value. In this paper, the application of SAP hydrogel in peripheral nerve injury repair is reviewed, and the latest progress in peptide composites and fabrication techniques are discussed.

Pectin-based injectable and biodegradable self-healing hydrogels for enhanced synergistic anticancer therapy.

We report a new injectable and biodegradable self-healing hydrogel that shows enhanced anticancer drug release property. The hydrogel was prepared based on biodegradable pectin aldehyde (pectin-CHO) and acylhydrazide functionalized polymer poly(N-isopropylacrylamide-stat-acylhydrazide) P(NIPAM-stat-AH). Due to the dynamic nature of acylhydrazone bonds, the hydrogel exhibits self-healing behavior and its mechanical properties can be regulated by the weight ratio of P(NIPAM-stat-AH) to pectin-CHO. The in vitro and in vivo experiments show the hydrogel has not only good biocompatibility and biodegradability, but also decreases the toxicity of the drugs to living body and exhibits controlled drug release behavior as synergetic anti-tumor drug delivery carriers. The results demonstrate that the pectin-based self-healing hydrogels are injectable, biodegradable, and self-healable that is promising for localized anti-tumor therapy. STATEMENT OF SIGNIFICANCE: Injectable hydrogels with self-healing property and biodegradability are excellent candidates as drug loading and release carrier for biomedical applications. However the pectin as a biobased material is always neglected in self-healing hydrogel preparation. In this study, we fabricated biodegradable self-healing hydrogels from aldehyde group bearing pectin (pectin-CHO) and thermo-responsive copolymer of P(NIPAM-stat-AH). The hydrogel showed sustained drug release behavior, good biocompatibility and biodegradability both in vitro and in vivo. The in vivo experiment shows that the hydrogel with coloaded DOX and CA4 has synergetic therapy to CT26 tumors and this kind of biodegradable hydrogel has great potential application in antitumor therapy.

Smart Hydrogel Bilayers Prepared by Irradiation.

Environment-responsive hydrogel actuators have attracted tremendous attention due to their intriguing properties. Gamma radiation has been considered as a green cross-linking process for hydrogel synthesis, as toxic cross-linking agents and initiators were not required. In this work, chitosan/agar/P(N-isopropyl acrylamide-co-acrylamide) (CS/agar/P(NIPAM-co-AM)) and CS/agar/Montmorillonite (MMT)/PNIPAM temperature-sensitive hydrogel bilayers were synthesized via gamma radiation at room temperature. The mechanical properties and temperature sensitivity of hydrogels under different agar content and irradiation doses were explored. The enhancement of the mechanical properties of the composite hydrogel can be attributed to the presence of agar and MMT. Due to the different temperature sensitivities provided by the two layers of hydrogel, they can move autonomously and act as a flexible gripper as the temperature changes. Thanks to the antibacterial properties of the hydrogel, their storage time and service life may be improved. The as prepared hydrogel bilayers have potential applications in control devices, soft robots, artificial muscles and other fields.

An injectable and biodegradable nano-photothermal DNA hydrogel enhances penetration and efficacy of tumor therapy.

The biological barrier of solid tumors hinders deep penetration of nanomedicine, constraining anticancer treatment. Moreover, the inherent multidrug resistance (MDR) of cancer tissues may further limit the efficacy of anti-tumor nanomedicine. We synthesized highly permeable, photothermal, injectable, and positively charged biodegradable nucleic acid hydrogel (DNA-gel) nanoparticles to deliver cancer drugs. The nanoparticles are derived from photothermal materials containing black phosphorus quantum dots (BPQDs). The intra-tumoral BPQDs improve the sensitivity of tumor cells to photothermal therapy (PTT) and photodynamic treatment (PDT). Tumor cells take up the positively charged and controllable size DNA-gel nanoparticles, facilitating easy penetration and translocation of the particles across and within the cells. Mouse models demonstrated the anti-tumor activity of the DNA gel nanoparticles in vivo. In particular, the DNA gel nanoparticles enhanced clearance of both small and large tumor masses. Just 20 days after treatment, the tumor masses had been cleared. Compared to DOX chemotherapy alone, the DNA-gel treatment also significantly reduced drug resistance and improved the overall survival of mice with orthotopic breast tumors (83.3%, 78 d). Therefore, DNA gel nanoparticles are safe and efficient supplements for cancer therapy.

Fabrication of self-healing hydrogel from quaternized N-[3(dimethylamino)propyl]methacrylamide copolymer for antimicrobial and drug release applications.

Self-healing hydrogels have attracted great attention in recent years because of their wide application in bioscience and biotechnology. In this study, P(DMAPMA-stat-DAA) were synthesized by Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization and quaternized to import antimicrobial properties. Then quaternized P(DMAPMA-stat-DAA) was used to prepare hydrogel containing acylhydrazone groups with Polyethylene oxide (PEO) diacylhydrazide as a cross-linking agent. The acylhydrazone groups imparted a variety of properties, including group responsiveness and self-healing properties to the hydrogel. At the same time, the quaternary ammonium endowed the hydrogel with the antimicrobial property. The mechanical property, self-healing properties, and antimicrobial property of hydrogels were investigated intensively. Results showed hydrogels formed in neutral conditions, and the luminescent property was introduced with PEO23 dinaphthhydrazide (DNH) cross-linking. The hydrogels showed a controlled pH-sensitive DOX·HC l and Ovalbumin (OVA) release profile. In addition, the hydrogel showed the antimicrobial property and may have important applications in the biomedical field in the near future.

Self-healing PEG-poly(aspartic acid) hydrogel with rapid shape recovery and drug release.

Self-healing hydrogels were prepared from hydrazide functionalized poly(aspartic acid) (PAsp). The polymer succinimide (PSI) was reacted with hydrazine and ethanolamine successively to obtain water soluble poly(aspartic acid) derivatives with hydrazide functional groups (PAEH). The hydrogel was prepared by cross-linking PAEH with poly(ethylene glycol) dialdehyde (PEG DA) under mild conditions without addition of catalyst. The rheological property and the self-healing property of the hydrogels were investigated intensively. The in vitro toxicity experiment showed the hydrogels have good bio-compatibility and the doxorubicin (DOX)-loaded hydrogels showed controlled release profile. Importantly, the hydrogel can still be degraded based on poly(aspartic acid) backbone. The bio-degradable poly(amino acid) based on self-healing hydrogel could have great potential application in bioscience including tissue repairing, drug loading and release.

Cellulose-based self-healing hydrogel through boronic ester bonds with excellent biocompatibility and conductivity.

Self-healing hydrogels based on degradable resources have developed rapidly in the past decade due to their extensive bioapplications with biosecurity. In this research, a new kind of cellulose-based self-healing hydrogel with bio-degradability is constructed through boronic ester linkage. The carboxyethyl cellulose-graft-phenylboronic acid (CMC-B(OH)2) was synthesized through condensation reaction conveniently and then hydrogels were prepared with dynamic boronic ester cross-linking. The chemical structures, microscopic morphologies, mechanical and self-healing properties of the hydrogels were investigated intensively through Fourier transform infrared (FT-IR) spectroscopy, rheological, SEM and tensile testing. The hydrogels formed instantly without any additional catalyst and exhibit excellent self-healing ability with good mechanical properties. Moreover, the hydrogels were applied for controlled release of doxorubicin (DOX·HCl) and showed a successive slow release profile. Importantly, the hydrogel exhibited excellent biocompatibility and show potential applications in controlled drug delivery, 3D cell culture and tissue engineering.

Self-Healing Hydrogels with both LCST and UCST through Cross-Linking Induced Thermo-Response.

Self-healing hydrogels have drawngreat attention in the past decade since the self-healing property is one of the characteristics of living creatures. In this study, poly(acrylamide-stat-diacetone acrylamide) P(AM-stat-DAA) with a pendant ketone group was synthesized from easy accessible monomers, and thermo-responsive self-healing hydrogels were prepared through a series of diacylhydrazide compounds cross-linking without any additional stimulus. Although the copolymers do not show thermo-response, the hydrogels became thermo-responsive andboth the lower critical solution temperature (LCST) and upper critical solution temperature (UCST) varied with the composition of the copolymer and structure of cross-linkers. With a dynamic covalent bond connection, the hydrogel showed gel-sol-gel transition triggered by acidity, redox, and ketone to acylhydrazide group ratios. This is another interesting cross-linking induced thermo-responsive (CIT) hydrogel with different properties compared to PNIPAM-based thermo-responsive hydrogels. The self-healing hydrogel with CIT properties could have great potential for application in areas related to bioscience, life simulation, and temperature switching.

Evaluation of expression levels and mechanism of complement activation.

The present study aimed to reveal the expression changes of complement system activation and complement activation product C3a receptor during acute myocardial infarction. Blood samples were collected from healthy individuals and from patients with coronary artery stenosis or acute myocardial infarction. The subjects received physical examination in hospital between January and July 2015 (n=5). Cytometric bead array was performed to measure the levels of complement system activation product anaphylatoxin C3a, C4a and C5a. Immunohistochemical investigations were performed in tissues of patients who underwent coronary artery bypass grafting between January and July 2015 to detect the expression of C3a receptor. The results of cytometric bead array showed that the content of complement activation products C3a, C4a and C5a in the plasma of patients with coronary artery stenosis and acute myocardial infarction were significantly higher than those of the control group (P<0.01). The results of immunoblotting suggested that the protein expression of C3a receptor in infarct tissues of patients with acute myocardial infarction was significantly higher than that of normal tissues adjacent to the infarcted area (P<0.05). There is complement system activation in patients with acute myocardial infarction. Additionally, the increase in the expression of complement C3a receptor in tissues of infarct area suggested that C3a-C3a receptor signaling pathway may be involved in the development of myocardial infarction.