ABSTRACT
Osteoid plays a crucial role in directing cell behavior and osteogenesis through its unique characteristics, including viscoelasticity and liquid crystal (LC) state. Thus, integrating osteoid-like features into 3D printing scaffolds proves to be a promising approach for personalized bone repair. Despite extensive research on viscoelasticity, the role of LC state in bone repair has been largely overlooked due to the scarcity of suitable LC materials. Moreover, the intricate interplay between LC state and viscoelasticity in osteogenesis remains poorly understood. Here, we developed innovative hydrogel scaffolds with osteoid-like LC state and viscoelasticity using digital light processing with a custom LC ink. By utilizing these LC scaffolds as 3D research models, we discovered that LC state mediates high protein clustering to expose accessible RGD motifs to trigger cell-protein interactions and osteogenic differentiation, while viscoelasticity operates via mechanotransduction pathways. Additionally, our investigation revealed a synergistic effect between LC state and viscoelasticity, amplifying cell-protein interactions and osteogenic mechanotransduction processes. Furthermore, the interesting mechanochromic response observed in the LC hydrogel scaffolds suggests their potential application in mechanosensing. Our findings shed light on the mechanisms and synergistic effects of LC state and viscoelasticity in osteoid on osteogenesis, offering valuable insights for the biomimetic design of bone repair scaffolds.
ABSTRACT
Bone defects can interfere with bone healing by disrupting the local environment, resulting in vascular damage and hypoxia. Under these conditions, insufficient oxygen availability is a significant factor that exacerbates disease by blocking angiogenesis or osteogenesis. Exosomes play a crucial role in intercellular communication and modulation of inflammation to aid bone regeneration. However, the distance between exosomes and areas of damage can hinder efficient bone generation and cell survival. To overcome this limitation, we fabricated a continuous oxygen-supplying composite scaffold, with the encapsulation of calcium peroxide in a polylactic acid three-dimensional (3D) printing construct (CPS), as both an oxygen source and hydroxyapatite (HAP) precursor. Furthermore, bone marrow mesenchymal stem cell (BMSC)-derived exosomes were incorporated into hyaluronic acid (HA) hydrogels to stimulate cell growth and modulate inflammation. The release of exosomes into cells leads to an increase in alkaline phosphatase production. In vivo results demonstrated that the composite scaffold regulated the inflammatory microenvironment, relieved tissue hypoxia, and promoted new bone formation. These results indicate that the synergistic effect of exosomes and oxygen promoted the proliferation of BMSCs, alleviated inflammation and exhibited excellent osteogenic properties. In conclusion, this osteogenic functional composite scaffold material offers a highly effective approach for bone repair.
Subject(s)
Bone Regeneration , Exosomes , Hyaluronic Acid , Hydrogels , Mesenchymal Stem Cells , Osteogenesis , Oxygen , Polyesters , Printing, Three-Dimensional , Tissue Scaffolds , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Polyesters/chemistry , Tissue Scaffolds/chemistry , Exosomes/metabolism , Bone Regeneration/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Osteogenesis/drug effects , Tissue Engineering/methods , Cell Proliferation/drug effects , Bone and Bones/drug effects , Bone and Bones/metabolismABSTRACT
Existing artificial periostea face many challenges, including difficult-to-replicate anisotropy in mechanics and structure, poor tissue adhesion, and neglected synergistic angiogenesis and osteogenesis. Here, inspired by natural wood (NW), a wood-derived elastic artificial periosteum is developed to mimic the structure and functions of natural periosteum, which combines an elastic wood (EW) skeleton, a polydopamine (PDA) binder layer, and layer-by-layer (LBL) biofunctional layers. Specifically, EW derived from NW is utilized as the anisotropic skeleton of artificial periosteum to guide cell directional behaviors, moreover, it also shows a similar elastic modulus and flexibility to natural periosteum. To further enhance its synergistic angiogenesis and osteogenesis, surface LBL biofunctional layers are designed to serve as spatiotemporal release platforms to achieve sequential and long-term release of pamidronate disodium (PDS) and deferoxamine (DFO), which are pre-encapsulated in chitosan (CS) and hyaluronic acid (HA) solutions, respectively. Furthermore, the combined effect of PDA coating and LBL biofunctional layers enables the periosteum to tightly adhere to damaged bone tissue. More importantly, this novel artificial periosteum can boost angiogenesis and bone formation in vitro and in vivo. This study opens up a new path for biomimetic design of artificial periosteum, and provides a feasible clinical strategy for bone repair.
Subject(s)
Osteogenesis , Periosteum , Wood , Periosteum/drug effects , Wood/chemistry , Animals , Osteogenesis/drug effects , Drug Liberation , Bone Regeneration/drug effects , Humans , Anisotropy , Indoles/chemistry , Indoles/pharmacology , Mice , Polymers/chemistry , Chitosan/chemistry , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Neovascularization, Physiologic/drug effectsABSTRACT
Natural bone exhibits a complex anisotropic and micro-nano hierarchical structure, more importantly, bone extracellular matrix (ECM) presents liquid crystal (LC) phase and viscoelastic characteristics, providing a unique microenvironment for guiding cell behavior and regulating osteogenesis. However, in bone tissue engineering scaffolds, the construction of bone-like ECM microenvironment with exquisite microstructure is still a great challenge. Here, we developed a novel polysaccharide LC hydrogel supported 3D printed poly(l-lactide) (PLLA) scaffold with bone-like ECM microenvironment and micro-nano aligned structure. First, we prepared a chitin whisker/chitosan polysaccharide LC precursor, and then infuse it into the pores of 3D printed PLLA scaffold, which was previously surface modified with a polydopamine layer. Next, the LC precursor was chemical cross-linked by genipin to form a hydrogel network with bone-like ECM viscoelasticity and LC phase in the scaffold. Subsequently, we performed directional freeze-casting on the composite scaffold to create oriented channels in the LC hydrogel. Finally, we soaked the composite scaffold in phytic acid to further physical cross-link the LC hydrogel through electrostatic interactions and impart antibacterial effects to the scaffold. The resultant biomimetic scaffold displays osteogenic activity, vascularization ability and antibacterial effect, and is expected to be a promising candidate for bone repair.
Subject(s)
Chitosan , Liquid Crystals , Animals , Chitosan/chemistry , Hydrogels/pharmacology , Hydrogels/metabolism , Chitin/pharmacology , Chitin/metabolism , Vibrissae , Tissue Scaffolds/chemistry , Bone Regeneration , Tissue Engineering , Osteogenesis , Extracellular Matrix/metabolism , Anti-Bacterial Agents/pharmacologyABSTRACT
Slow healing at the tendon-bone interface is a prominent factor in the failure of tendon repair surgeries. The development of functional biomaterials with 3D gradient structures is urgently needed to improve tendon-bone integration. The crystalline form of hydroxyapatite (HAP) has a crucial impact on cell behavior, which directly influences protein adsorption, such as bone morphogenetic protein 2, the adhesion, proliferation, and osteogenic differentiation with cells. This work aimed to generate gradient mineral structures in situ by stabilizing calcium and phosphate ions using a polymer-induced liquid precursor process. To regulate the crystalline growth of HAP at the interface of ß-chitin, this work made use of the surface properties of the organic matrix found in cuttlefish bone. These techniques allowed us to prepare an organic-inorganic composite gradient scaffold comprising plate-like HAP mineralized in situ on the surface of the scaffold and fibrous HAP in the scaffold's interior. Organic-inorganic composite gradient materials are anticipated for use in tendon-bone healing produced via the in situ construction of gradient-distributed HAP mineralization layers having varying crystalline morphologies on chitin scaffolds that possess a three-dimensional bionic structure.
Subject(s)
Durapatite , Osteogenesis , Durapatite/chemistry , Tissue Scaffolds/chemistry , Chitin , Bionics , Tissue EngineeringABSTRACT
Tissue-engineered poly(l-lactide) (PLLA) scaffolds have been widely used to treat bone defects; however, poor biological activities have always been key challenges for its further application. To address this issue, introducing bioactive drugs or factors is the most commonly used method, but there are often many problems such as high cost, uncontrollable and monotonous drug activity, and poor bioavailability. Here, a drug-free 3D printing PLLA scaffold with a triple-effect combination induced by surface-modified copper-doped layered double hydroxides (Cu-LDHs) is proposed. In the early stage of scaffold implantation, Cu-LDHs exert a photothermal therapy (PTT) effect to generate high temperature to effectively prevent bacterial infection. In the later stage, Cu-LDHs can further have a mild hyperthermia (MHT) effect to stimulate angiogenesis and osteogenic differentiation, demonstrating excellent vascularization and osteogenic activity. More importantly, with the degradation of Cu-LDHs, the released Cu2+ and Mg2+ provide an ion microenvironment effect and further synergize with the MHT effect to stimulate angiogenesis and osteogenic differentiation, thus more effectively promoting the healing of bone tissue. This triple-effect combined scaffold exhibits outstanding antibacterial, osteogenic, and angiogenic activities, as well as the advantages of low cost, convenient procedure, and long-term efficacy, and is expected to provide a promising strategy for clinical repair of bone defects.
Subject(s)
Osteogenesis , Tissue Scaffolds , Copper/pharmacology , Bone Regeneration , Hydroxides/pharmacology , Printing, Three-DimensionalABSTRACT
Chronic diabetic wound healing remains a formidable challenge due to susceptibility to bacterial infection, excessive oxidative stress, and poor angiogenesis. To address these issues, a sodium alginate (SA) based photothermal hydrogel dressing with multifunction was fabricated to facilitate wound treatment. Ceria nanoparticles (CeO2NPs) was synthesized, and their antibacterial performance by near-infrared light triggered photothermal effects was first studied and verified in this work. In addition, to release CeO2NPs to achieve antioxidation and pro-vascularization, thermosensitive gelatin (Gel) was utilized to embed the nanoparticles in advance and then composited in SA hydrogel networks. SA network was finally strengthened by acid soaking to form partially crystalline regions to act as natural crosslinkers. Results showed that the Gel/SA/CeO2 hydrogel displayed temperature-responsive release of CeO2NPs, significant antibacterial and antioxidative activity, as well as the ability to remove without injury and promote infected diabetic wound healing with low cytotoxicity, according to antibacterial investigations, cell studies, and in vivo animal studies. This research offers not only a successful method for quickening the healing of diabetic wounds but also a fresh approach to the general use of CeO2NPs.
ABSTRACT
Inspired by the similarity of anisotropic channels in wood to the canals of bone, the elastic wood-derived (EW) scaffolds with anisotropic channels were prepared via simple delignification treatment of natural wood (NW). We hypothesize that the degree of delignification will lead to differences in mechanical properties of scaffolds, which in turn directly affect the behaviors and fate of stem cells. The delignification process did not destroy the anisotropic channel structure of the scaffolds, but endowed the scaffolds with good elasticity and rapid stress relaxation. Interestingly, the micron-scale anisotropic channels of the scaffolds can highly promote the polarization of cells along the direction of channels. We also found that the alkaline phosphatase of EW scaffold can reach to about 13.1 U/gprot, which was about double that of NW scaffold. Moreover, the longer the delignification time, the better the osteogenic activity of the EW scaffolds. We further hypothesize that the osteogenic activity of scaffolds is related to the stress relaxation properties. The immunofluorescence staining showed that when the stress relaxation time of scaffold was shortened to about 10 s, the nuclear ratio of YAP of scaffold increased to 0.22, which well supports our hypothesis.
Subject(s)
Cues , Osteogenesis , Alkaline Phosphatase , Anisotropy , Cell DifferentiationABSTRACT
Chitin can self-assemble into a liquid crystal phase with supramolecular chirality and Bouligand structure, which is widely found in the exoskeletons of arthropods. However, bionically replicating this structure via the self-assembly of chitin whiskers (CHWs) is still a challenge. Here, the effects of several internal and external parameters on the self-assembly of CHWs were revealed based on liquid crystal phase, chirality, Bouligand structure, and rheological properties. The formation of chiral liquid crystal phase and Bouligand structure largely depends on the concentration of CHWs and, meanwhile, is affected by the aspect ratio and zeta potential of CHWs and the self-assembly time. Impressively, introducing electrolytes and changing pH significantly affect the thickness of the electrical double layer, thereby also affecting the self-assembly of CHWs. This study offers a comprehensive understanding of CHWs' self-assembly process, which is beneficial for the bionic design of new nature-inspired functional materials with chiral characteristic and Bouligand structure.
Subject(s)
Arthropods , Chitin , Animals , Chitin/chemistry , Vibrissae , ElectricityABSTRACT
While pioneering methods have demonstrated that bacterial N-acyl homoserine lactone (AHL) signaling molecules can influence the growth and self-aggregation of suspended microalgae, whether AHLs can affect the initial adhesion to a carrier has remained an open question. Here we revealed that the microalgae exhibited different adhesion potential under AHL mediation, where the performance was affiliated to both AHL types and concentrations. The result can be well explained by the interaction energy theory, where the energy barrier between the carriers and the cells varied due to AHL mediation. Depth analyses revealed that AHL acted through modifying the properties of the surface electron donor of the cells, which were dependent upon three major components, i.e., extracellular protein (PN) secretion, the PN secondary structure, and the PN amino acid composition. These findings expand the known diversity of AHLs mediation on microalgal initial adhesion and metabolisms, which may interface with other major cycles and become helpful to theoretically guide the application of AHLs in microalgal culture and harvesting.
Subject(s)
Acyl-Butyrolactones , Microalgae , 4-Butyrolactone/chemistry , 4-Butyrolactone/metabolism , Signal Transduction , BiofilmsABSTRACT
Excessive oxidative stress and inflammation often impede wound healing and ultimately lead to excessive skin fibrosis formation. It was known that the structural properties of biomaterials can affect the healing and immune response of surrounding tissues. In this work, a composite structure of Mn-Si-chitooligosaccharides (COS) was designed (COS@Mn-MSN) and the ability of regulating wound microenvironment for inhibiting skin fibrosis was investigated. In order to reduce the negative effects of Mn, the nano-level Mn was doped into MSN to minimize its content. The results show that Mn in COS@Mn-MSN showed significant ability of scavenging excess intracellular ROS within 1 d. The Si released from COS@Mn-MSN can shift M2 macrophage polarization in the later stage (1-3 d), showing anti-inflammatory effect. Macrophage (RAW264.7) were activated alternatively by COS released from COS@Mn-MSN, with upregulated expression of anti-inflammatory factors (IL-10 and CD206) and downregulated expression of pro-inflammatory factors (TNF-α, CD80, and IL-1ß) in the whole time. The expression of fibrosis associated factor TGF-ß1 and CD26 in fibroblast cells (L929) were inhibited by COS and Si. Besides, the inflammatory microenvironment mediated by COS@Mn-MSN downregulated Smad-7 gene expression and upregulated Col-1α gene expression. With the function of reducing oxidative stress (0-1 d), the TGF-ß1 inhibition (1-3 d) and anti-inflammatory effects (0-3 d), COS@Mn-MSN could inhibit excessive skin fibrosis formation mediated with ROS/TGF-ß1/Smad7 signal. Therefore, the prepared COS@Mn-MSN shows great potential to active scarless wound therapy.
Subject(s)
Skin Diseases , Transforming Growth Factor beta1 , Humans , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/pharmacology , Reactive Oxygen Species/pharmacology , Signal Transduction , Fibrosis , Wound Healing , Chitin/pharmacologyABSTRACT
Currently, hemoperfusion is clinically the most rapid and effective treatment for removing toxins from the blood. The core of hemoperfusion is the sorbent inside the hemoperfusion device. Due to the complex composition of the blood, adsorbents tend to adsorb substances such as proteins in the blood (non-specific adsorption) while adsorbing toxins. Hyperbilirubinemia is caused by excessive levels of bilirubin in the human blood, causing irreversible damage to the patient's brain and nervous system, and even leading to death. High adsorption and high biocompatibility adsorbents with specific bilirubin adsorption are urgently needed to treat hyperbilirubinemia. Herein, poly(L-arginine) (PLA) which can specifically adsorb bilirubin, was introduced into chitin/MXene (Ch/MX) composite aerogel spheres. Ch/MX/PLA prepared by supercritical CO2 technology had higher mechanical properties than Ch/MX and can withstand 50,000 times its own weight. The in vitro simulated hemoperfusion test showed that the adsorption capacity of Ch/MX/PLA was as high as 596.31 mg/g, which was 15.38 % higher than that of Ch/MX. Binary and ternary competitive adsorption tests showed that Ch/MX/PLA also had good adsorption capacity in the presence of a variety of interfering molecules. In addition, hemolysis rate testing and CCK-8 testing confirmed that Ch/MX/PLA had better biocompatibility and hemocompatibility. Ch/MX/PLA can meet the required properties of clinical hemoperfusion sorbents and has the ability to produce mass production. It has good application potential in the clinical treatment of hyperbilirubinemia.
Subject(s)
Bilirubin , Chitin , Humans , Adsorption , Hyperbilirubinemia/therapy , PolyestersABSTRACT
Reliable, fast and switchable gluing modes are critically important in medical adhesives and intelligent climbing robot applications. The octopus-bionic patch has attracted the attention of many scholars. The suction cup structure of the octopus achieves adhesion through differential pressure, showing strong adhesion in both dry and wet environments. However, the construction of the octopus-bionic patch remains limited in terms of adaptability, personalization and mass production. Herein, a composite hydrogel consisting of gelatin methacryloyl (GelMA), polyethylene glycol diacrylate (PEGDA) and acrylamide (AAM) was developed, and a structure mimicking the octopus sucker was constructed by digital light processing (DLP). The obtained octopus-bionic patch has strong adhesion, good biocompatibility and multi-functionality. Compared with the template method in most studies, the octopus-bionic patch constructed by the DLP printing method has the advantages of customizability and low cost. In addition, the DLP printing method endows the patch surface with an octopus-like groove structure for a better bionic effect.
Subject(s)
Octopodiformes , Animals , Bionics , Curing Lights, Dental , Light-Curing of Dental Adhesives , Printing, Three-DimensionalABSTRACT
Unsatisfactory solid-tumor penetration or rapid metabolism of nanomaterials limits their therapeutic efficacy. Here, we designed an injectable thiolated hyaluronate (HA-SH) hydrogel as a stable drug-releasing platform for in situ tumor treatment. Biodegradable star-shaped polylactide (S-PLLA) was first synthesized and fabricated to porous microspheres to encapsulate hydrophobic curcumin (Cur@S-PLLA), which was then blended with hydrophilic doxorubicin (Dox) and the HA-SH precursor to form composite in situ formable hydrogels [Cur@S-PLLA/(Dox)HA-SH]. The results showed that adding the microspheres improved the performance of the hydrogel, such as decreasing the gelation time from 1080 s to 960 s and also the swelling ratio. The mechanical strength increased from 27 to 45 kPa. In addition, the double drug system guaranteed a sustained release of drugs, releasing Dox at the early stage, with the continuous later release of Cur after gel swelling or S-PLLA degradation to achieve long-lasting tumor suppression, which inhibits the survival of cancer cells. The inhibitory effects of the hydrogels on MCF-7 were studied. The cell activity in the double-loaded hydrogel was significantly lower than that of the control groups, and apparent dead cells appeared in 2 days and fewer living cells with time. Flow cytometry revealed that the Cur@S-PLLA/(Dox)HA-SH group had the highest apoptosis ratio of 86.60% at 12 h, and the drugs caused the cell cycle to be blocked in phase M to reduce cell division. In summary, the innovative release platform is expected to be used in long-lasting tumor suppression and provides more ideas for the design of drug carriers.
ABSTRACT
Chronic wound unhealing is a common complication in diabetic patients, which is mainly caused by tissue hypoxia, slow vascular recovery, and a long period of inflammation. Here we present a sprayable alginate hydrogel (SA) dressing consisting of oxygen-productive (CP) microspheres and exosomes (EXO) to promote local oxygen generation, accelerate macrophage towards M2 polarization, and improve cell proliferation in diabetic wounds. Results show that the release of oxygen continues for up to 7 days, reducing the expression of hypoxic factors in fibroblasts. In vivo, the diabetic wounds experiment showed that the CP/EXO/SA dressing apparently accelerated full-thickness wound healing characteristics such as the promotion of wound healing efficiency, rapid re-epithelization, favorable collagen deposition, abundant angiogenesis at the wound beds, and shortened inflammation period. EXO synergistic oxygen (CP/EXO/SA) dressing suggests a promising treatment measure for diabetic wounds.
Subject(s)
Diabetes Mellitus , Exosomes , Humans , Hydrogels/metabolism , Oxygen/metabolism , Exosomes/metabolism , Alginates/metabolism , Diabetes Mellitus/drug therapy , Diabetes Mellitus/metabolism , Bandages , Inflammation/metabolismABSTRACT
Scaffold-based tissue engineering is a promising strategy to address the rapidly growing demand for bone implants, but developing scaffolds with bone extracellular matrix-like structures, suitable mechanical properties, and multiple biological activities remains a huge challenge. Here, it is aimed to develop a wood-derived composite scaffold with an anisotropic porous structure, high elasticity, and good antibacterial, osteogenic, and angiogenic activities. First, natural wood is treated with an alkaline solution to obtain a wood-derived scaffold with an oriented cellulose skeleton and high elasticity, which can not only simulate collagen fiber skeleton in bone tissue but also greatly improve the convenience of clinical implantation. Subsequently, chitosan quaternary ammonium salt (CQS) and dimethyloxalylglycine (DMOG) are further modified on the wood-derived elastic scaffold through a polydopamine layer. Among them, CQS endows the scaffold with good antibacterial activity, while DMOG significantly improves the scaffold's osteogenic and angiogenic activities. Interestingly, the mechanical characteristics of the scaffolds and the modified DMOG can synergistically enhance the expression of yes-associated protein/transcriptional co-activator with PDZ binding motif signaling pathway, thereby effectively promoting osteogenic differentiation. Therefore, this wood-derived composite scaffold is expected to have potential application in the treatment of bone defects.
Subject(s)
Chitosan , Mesenchymal Stem Cells , Tissue Scaffolds/chemistry , Osteogenesis , Wood , Tissue Engineering , Chitosan/chemistry , Anti-Bacterial Agents/pharmacology , Bone Regeneration , Cell DifferentiationABSTRACT
As a particular cell niche, natural bone extracellular matrix (ECM) is an organic-inorganic composite material formed by mineralization of liquid crystal (LC) collagen fiber network. However, designing bone repair materials that highly imitate the LC characteristic and composite components of natural bone ECM is a great challenge. Here, we report a novel kind of bone ECM-inspired biomineralization chitin whisker LC hydrogels. First, photocurable chitin whisker LC hydrogels with bone ECM-like chiral nematic LC state and viscoelasticity are created. Next, biomineralization, guided by LC hydrogels, is carried out to truly mimic the mineralization process of natural bone, so as to obtain the organic-inorganic composite materials with bone ECM-like microenvironment. The chitin whisker LC hydrogels exhibit superior biomineralization, protein adsorption and osteogenesis ability, more importantly, LC hydrogel with negatively charged -COOH groups is more conducive to biomineralization and shows more desirable osteogenic activity than that with positively charged -NH2 groups. Notably, compared with the pristine LC hydrogels, the biomineralization LC hydrogels display more favorable osteogenesis ability due to their bone ECM-like LC texture and bone-like hydroxyapatite. This study opens an avenue toward the design of bone ECM-inspired biomineralization chitin whisker LC hydrogels for bone regeneration.
Subject(s)
Hydrogels , Liquid Crystals , Animals , Hydrogels/chemistry , Chitin/chemistry , Biomineralization , Vibrissae , Bone Regeneration , Osteogenesis , Extracellular MatrixABSTRACT
To achieve the pH-responsive release of metformin in tumor acidic microenvironment, we prepared OHA-Met by covalently grafting metformin (Met) onto oxidized hyaluronic acid (OHA) through imine bonds, and then prepared carboxymethyl chitosan (CMCS)/OHA-Met drug loaded hydrogels. The CMCS/OHA-Met hydrogels showed the in-situ injection performance. At pH = 7.4, the cumulative release rate of metformin from CMCS/OHA-Met20 hydrogel was 42.7 ± 2.6 % in 6 h, and the release tended to balance after 72 h. At pH = 5.5, the release kept constant and the cumulative release rate was 79.3 ± 4.7 % at 6 h, showing good pH-responsive behavior. Metformin induced apoptosis of MCF-7 cells through the caspase 3/PARP pathway. CMCS/OHA-Met20 hydrogel could effectively kill MCF-7 cells, while reducing the cytotoxicity of free metformin to L929 cells. In vivo breast cancer recurrence experiments showed CMCS/OHA-Met20 hydrogel could achieve local injection and pH-responsive smart drug delivery at the tumor resection site, inhibiting breast cancer recurrence. Compared with direct administration, CMCS/OHA-Met20 hydrogel reduced the metformin dosage, frequency of administration and systemic side effects.
Subject(s)
Breast Neoplasms , Chitosan , Humans , Female , Breast Neoplasms/drug therapy , Hyaluronic Acid/chemistry , Hydrogels/pharmacology , Hydrogels/chemistry , Drug Delivery Systems , Hydrogen-Ion Concentration , Chitosan/chemistry , Tumor MicroenvironmentABSTRACT
Monitoring hydroxyl radical (â¢OH) fluctuation is of great importance to study some relative pathological processes and to predict early diagnosis of diseases. Efficient â¢OH-responsive fluorescent sensors based on carbon dots (CDs) have been reported, but most researches have focused on the new strategies for the synthesis and doping of the CDs. Herein, a kind of biomass CDs (F-CDs) with Flammulina velutipes (F. velutipes) as the carbon source was prepared by a one-step hydrothermal method without any additional modification. The prepared F-CDs have remarkable sensitivity and selectivity and there is a good linear relationship from 0 to 12 µM with a low detection limit of 95 nM for quantitative â¢OH assay. With excitation-independent emission, favourable biocompatibility and low toxicity, the F-CDs can penetrate cell membranes as â¢OH-responsive fluorescent sensors to detect intracellular â¢OH in A549 cells stimulated by phorbol 12-myristate 13-acetate (PMA) and successfully monitor the â¢OH concentration levels by the corresponding fluorescence change. Given the combined benefits of the green and eco-friendly approach, the F-CDs show promise as novel theranostics tools for early detection and treatment of related diseases.
Subject(s)
Flammulina , Quantum Dots , Fluorescence , Quantum Dots/toxicity , Hydroxyl Radical , Carbon , Fluorescent Dyes/pharmacologyABSTRACT
We develop a kind of photocurable liquid crystal hydrogels with bone extracellular matrix (ECM)-like liquid crystal state and viscoelasticity, as well as different chargeability. First, positively charged chitin whiskers (CHWs) and negatively charged maleic anhydride chitin whiskers (mCHWs) were prepared, which further self-assemble to form chiral nematic liquid crystals under ultrasonic treatment, respectively. Subsequently, poly (ethylene glycol) diacrylate (PEGDA) and photo initiator were added, and then two kinds of liquid crystal hydrogels with bone ECM-like viscoelasticity and different chargeability were prepared under ultraviolet (UV) irradiation. Benefiting from the bone ECM-like liquid crystal state and viscoelasticity, the prepared liquid crystal hydrogels exhibit remarkable cell affinity and osteogenic ability. Moreover, the liquid crystal hydrogel with negatively charged mCHWs is more favorable for cell adhesion, spreading and osteogenic differentiation than that with positively charged CHWs. This work provides a promising strategy to prepare the hydrogels with bone ECM-like liquid crystal properties and viscoelasticity for bone repair.