EMX2 inhibits clear cell renal cell carcinoma progress via modulating Akt/FOXO3a pathway.

Empty spiracles homeobox 2 (EMX2) is initially identified as a key transcription factor that plays an essential role in the regulation of neuronal development and some brain disorders. Recently, several studies emphasized that EMX2 could as a tumor suppressor, but its role in human clear cell renal cell carcinoma (ccRCC) remains unclear. In the present study, we investigated the role and underlying mechanism of EMX2 in the regulation of ccRCC progress. Our results demonstrated that EMX2 expression was markedly decreased in ccRCC tissues and cell lines, and low EMX2 expression predicted the poor prognosis of ccRCC patients. In addition, forced expression of EMX2 significantly inhibited the cell growth, migration, and invasion in vitro, as well as ccRCC tumor growth in nude mice, via, at least in part, regulating Akt/FOXO3a pathway. In detail, EMX2 could attenuate the phosphorylation levels of Akt and FOXO3a, and increase FOXO3a expression without affecting total Akt expression in vivo and in vitro. Meanwhile, shRNA-mediated knockdown of FOXO3a expression could obviously attenuate the effects of EMX2 on cell growth, migration, invasion, and tumor growth. Furthermore, EMX2 could significantly attenuate the interaction between Akt and FOXO3a. Taken together, our results demonstrated that EMX2 could inhibit ccRCC progress through, at least in part, modulating Akt/FOXO3a signaling pathway, thus representing a novel role and underlying mechanism of EMX2 in the regulation of ccRCC progress.

Anisotropic Microspheres-Cryogel Composites Loaded with Magnesium l-Threonate Promote Osteogenesis, Angiogenesis, and Neurogenesis for Repairing Bone Defects.

To achieve osteogenesis, angiogenesis, and neurogenesis for repairing bone defects, we constructed an anisotropic microspheres-cryogel composite loaded with magnesium l-threonate (MgT). These composites were prepared by the photo-click reaction of norbornene-modified gelatin (GB) in the presence of MgT-loaded microspheres through the bidirectional freezing method. The composites possessed an anisotropic macroporous (around 100 µm) structure and sustained release of bioactive Mg2+, which facilitate vascular ingrowth. These composites could significantly promote osteogenic differentiation of bone marrow mesenchymal stem cells, tubular formation of human umbilical vein vessel endothelial cells, and neuronal differentiation in vitro. Additionally, these composites significantly promoted early vascularization and neurogenesis as well as bone regeneration in the rat femoral condyle defects. In conclusion, owing to the anisotropic macroporous microstructure and bioactive MgT, these composites could simultaneously promote bone, blood vessel, and nerve regeneration, showing great potential for bone tissue engineering.

Biomimetic cryogel promotes the repair of osteoporotic bone defects through altering the ROS niche via down-regulating the ROMO1.

Osteoporosis is a systemic bone disease that is prone to fractures due to decreased bone density and bone quality, and delayed union or nonunion often occurs in osteoporotic fractures. Therefore, it is particularly important to develop tissue engineering materials to promote osteoporotic fracture healing. In this study, a series of biomimetic cryogels prepared from the decellularized extracellular matrix (dECM), methacrylate gelatin (GelMA), and carboxymethyl chitosan (CMCS) via unidirectional freezing, photo- and genipin crosslinking were applied for the regeneration of osteoporotic fractures. Specifically, dECM extracted from normal or osteoporotic rats was applied for the preparation of the cryogels, named as GC-Normal dECM or GC-OVX dECM, respectively. It was verified that the GC-Normal dECM demonstrated superior performance in promoting the proliferation of BMSCs isolated from osteoporotic rats (OVX-BMSCs), and the differentiation of OVX-BMSCs into osteoblasts both in vitro and in vivo. RNA sequencing and further verifications confirmed that GC-Normal dECM cryogel could scavenge the intracellular reactive oxygen species (ROS) in OVX-BMSCs to accelerate the regeneration of osteoporotic fracture by down-regulating the reactive oxygen species modulator 1 (Romo1). The results indicated that by regulating the ROS niche of OVX-BMSCs, biomimetic the GC-Normal dECM cryogel was expected to be a clinical candidate for repairing osteoporotic bone defects.

Multifunctional Injectable Microspheres Containing "Naturally-Derived" Photothermal Transducer for Synergistic Physical and Chemical Treating of Acute Osteomyelitis through Sequential Immunomodulation.

Osteomyelitis induced by Staphylococcus aureus (S. aureus) is a persistent and deep-seated infection that affects bone tissue. The main challenges in treating osteomyelitis include antibiotic resistance, systemic toxicity, and the need for multiple recurrent surgeries. An ideal therapeutic strategy involves the development of materials that combine physical, chemical, and immunomodulatory synergistic effects. In this work, we prepared injectable microspheres consisting of an interpenetrating network of ionic-cross-linked sodium alginate (SA) and genipin (Gp)-cross-linked gelatin (Gel) incorporated with tannic acid (TA) and copper ions (Cu2+). The Gp-cross-linked Gel acted as a "naturally-derived" photothermal therapy (PTT) agent. The results showed that the microspheres exhibited efficient and rapid bactericidal effects against both S. aureus and Escherichia coli (E. coli) under the irradiation of near-infrared light at 808 nm wavelength; moreover, the release of Cu2+ also induced sustained inhibitory effects against bacteria during the nonirradiation period. The in vitro cell culture results indicated that when combined with PTT, the microspheres could adaptively modulate macrophage M1 and M2 phenotypes in sequence. Additionally, these microspheres were found to enhance the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In vivo studies conducted in a rat femur osteomyelitis model with bone defects showed that under multiple laser irradiation the microspheres effectively controlled bacterial infection, improved the pathological immune microenvironment, and significantly enhanced the repair and regeneration of bone tissues in the affected area.

The BRAF V600E Mutation and Clinicopathological Changes Among Patients With Hashimoto thyroiditis, Papillary Thyroid Carcinoma With Hashimoto Thyroiditis, and Nodular Goiter.

The study aimed to investigate the BRAF V600E mutation and clinicopathological changes among patients with Hashimoto thyroiditis (HT), papillary thyroid carcinoma (PTC) with Hashimoto thyroiditis (HT), or nodular goiter (NG). A total of 87 patients with the BRAF V600E mutation who were diagnosed with HT (including with hyperplasia dysplasia), PTC with HT, and PTC with NG were enrolled. Clinical data, concentrations of antithyroglobulin antibodies (TGAb) and thyroid microsomal antibodies (TMAb) in the serum thyroid-function levels, and the result presence of the BRAF V600E mutation were retrospectively analyzed. There were significant differences in the BRAF V600E mutation rates between the HT and PTC with HT groups (P <0.05) and the HT and PTC with NG groups (P <0.05), whereas no significant difference was found between the PTC with HT and PTC with NG groups. There was no difference in incidences of PTC between HT with elevated TGAb and TMAb group and those with baseline levels. The incidence of multifocal PTC was higher in the PTC with HT group; however, the difference was not significant. Our findings documented that BRAF mutation distinguished between the benign HT and the malignant PTC groups. The serum levels of TGAb and TMAb autoantibodies did not directly correlate with PTC in the background of HT. HT and NG may similarly contribute to the pathogenesis of PTC.

Biomineralization-Inspired Anti-Caries Strategy Based on Multifunctional Nanogels as Mineral Feedstock Carriers.

Background: Dentin caries remains a significant public concern, with no clinically viable material that effectively combines remineralization and antimicrobial properties. To address this issue, this study focused on the development of a bio-inspired multifunctional nanogel with both antibacterial and biomineralization properties. Methods: First, p(NIPAm-co-DMC) (PNPDC) copolymers were synthesized from N-isopropylacrylamide (NIPAm) and 2-methacryloyloxyethyl-trimethyl ammonium chloride (DMC). Subsequently, PNPDC was combined with γ-polyglutamic acid (γ-PGA) through physical cross-linking to form nanogels. These nanogels served as templates for the mineralization of calcium phosphate (Cap), resulting in Cap-loaded PNPDC/PGA nanogels. The nanogels were characterized using various techniques, including TEM, particle tracking analysis, XRD, and FTIR. The release properties of ions were also assessed. In addition, the antibacterial properties of the Cap-loaded PNPDC/PGA nanogels were evaluated using the broth microdilution method and a biofilm formation assay. The remineralization effects were examined on both demineralized dentin and type I collagen in vitro. Results: PNPDC/PGA nanogels were successfully synthesized and loaded with Cap. The diameter of the Cap-loaded PNPDC/PGA nanogels was measured as 196.5 nm at 25°C and 162.3 nm at 37°C. These Cap-loaded nanogels released Ca2+ and PO43- ions quickly, effectively blocking dental tubules with a depth of 10 µm and promoting the remineralization of demineralized dentin within 7 days. Additionally, they facilitated the heavy intrafibrillar mineralization of type I collagen within 3 days. Moreover, the Cap-loaded nanogels exhibited MIC50 and MIC90 values of 12.5 and 50 mg/mL against Streptococcus mutans, respectively, with an MBC value of 100 mg/mL. At a concentration of 50 mg/mL, the Cap-loaded nanogels also demonstrated potent inhibitory effects on biofilm formation by Streptococcus mutans while maintaining good biocompatibility. Conclusion: Cap-loaded PNPDC/PGA nanogels are a multifunctional biomimetic system with antibacterial and dentin remineralization effects. This strategy of using antibacterial nanogels as mineral feedstock carriers offered fresh insight into the clinical management of caries.

Study on the Friction and Wear Properties of PEEK against Cortical Bone Tissue Under Different Lubricating Conditions.

The tribological behavior between orthopedic implants and cortical bone is important but usually neglected. Poly(ether-ether-ketone) (PEEK) is a promising material for orthopedic applications. To further understand and improve the interfacial tribological properties between PEEK implant and host bone tissue, a PEEK-cortical bone tribo-pair is designed and fabricated. The frictional and wear performance of such tribo-pair is investigated under different lubricants, i.e., simulated body fluid (SBF), calf serum (CS), hyaluronic acid (HA), and mucin (MUC). The results suggest that MUC solution can be utilized as an artificial natural synovial fluid to improve the tribological properties of PEEK-based implants.

ß-Arrestin2 promotes docetaxel resistance of castration-resistant prostate cancer via promoting hnRNP A1-mediated PKM2 alternative splicing.

PURPOSE: To investigate the influence of ß-arrestin2 on the docetaxel resistance in castration-resistant prostate cancer (CRPC) and elucidate the underlying molecular mechanisms. METHODS: PC3 and DU145 cells with stable ß-arrestin2 overexpression and C4-2 cells with stable ß-arrestin2 knockdown, were constructed via using lentivirus and puromycin selection. MTT and colony formation assays were carried out to investigate the effect of ß-arrestin2 expression on the docetaxel resistance of CRPC cells. Glycolysis analysis was used to assess the glycolytic capacity modulated by ß-arrestin2. GO enrichment analysis, gene set enrichment analysis and Spearman correlation test were carried out to explore the potential biological function and mechanism via using public data from GEO and TCGA. The expressions of PKM2, Phospho-PKM2, Phospho-ERK1/2 and hnRNP A1 were detected by western blot. Functional blocking experiments were carried out to confirm the roles of PKM2 and hnRNP A1 in the regulation of ß-arrestin2's biological functions via silencing PKM2 or hnRNP A1 expression in cells with stable ß-arrestin2 overexpression. Finally, nude mice xenograft models were established to confirm the experimental results of cell experiments. RESULTS: ß-Arrestin2 significantly decreased the sensitivity of CRPC cells to docetaxel stimulation, through enhancing the phosphorylation and expression of PKM2. Additionally, ß-arrestin2 increased PKM2 phosphorylation via the ERK1/2 signaling pathway and induced PKM2 expression in a post-transcriptional manner through an hnRNP A1-dependent PKM alternative splicing mechanism, rather than by inhibiting its ubiquitination degradation. CONCLUSION: Our findings indicate that the ß-arrestin2/hnRNP A1/PKM2 pathway could be a promising target for treating docetaxel-resistant CRPC.

[Three-dimensional morphological study of the effect of false acetabulum on the femoral structure in Crowe type â £ developmental dysplasia of the hip].

Objective: To explore the effect of false acetabulum on the development and anatomical morphology of proximal femur in Crowe type Ⅳ developmental dysplasia of the hip (DDH), providing a theoretical basis for the development of femoral reconstruction strategy and prosthesis selection for total hip arthroplasty. Methods: The medical records of 47 patients (54 hips) with Crowe type Ⅳ DDH between February 2008 and March 2020 were retrospectively analyzed, of which 21 patients (26 hips) were Crowe type Ⅳa (type Ⅳa group) and 26 patients (28 hips) were Crowe type Ⅳb (type Ⅳb group). There was no significant difference in general data such as gender, age, height, weight, body mass index, and side between the two groups ( P>0.05), which were comparable. The height of femoral head dislocation, the height of pelvis, and the proportion of dislocation were measured based on preoperative anteroposterior pelvic X-ray film. Based on the preoperative femoral CT scan data, the anatomical parameters of the femur and femoral medullary cavity were measured after three-dimensional reconstruction using Mimics19.0 software to calculate the canal fare index; and the femoral medullary cavity parameters were matched with the modular S-ROM prosthesis parameters. Results: The results of X-ray film measurement showed that the height of femoral head dislocation and the proportion of dislocation in type Ⅳa group were significantly higher than those in type Ⅳb group ( P<0.05). There was no significant difference in the height of pelvis between the two groups ( P>0.05). The results of CT three-dimensional reconstruction measurements showed that compared with the type Ⅳb group, the type Ⅳa group had less isthmus height, smaller femoral head, shorter femoral neck, narrower neck-shaft angle, increased anteversion angle, and higher greater trochanter, and the differences were significant ( P<0.05). There was no significant difference in the height of femoral head, femoral offset, and height difference between greater trochanter and femoral head between the two groups ( P>0.05). There was no significant difference in the mediolateral width (ML), anteroposterior width (AP), and diameter of the isthmus (Ci level) and the AP of the medullary cavity in the plane 40 mm distal to the most prominent point on the medial side of the lesser trochanter (C -40 level) ( P>0.05), and the size of medullary cavity was significantly smaller in type Ⅳa group than in type Ⅳb group at the other levels ( P<0.05). Compared with the type Ⅳb group, the difference between the outer diameter of the prosthetic sleeve and the diameter of the medullary cavity fitting circle in the plane where the center of femoral head rotation was located from the medial most prominent point of the lesser trochanter (C 0 level) in type Ⅳa group was smaller, and the proportion of negative values was greater ( P<0.05). The difference between the longest diameter of the prosthetic sleeve triangle and the ML of the medullary cavity in the plane 10 mm proximal to the most prominent point on the medial side of the lesser trochanter (C +10 level) in type Ⅳa group was smaller, and the proportion of negative values was greater ( P<0.05). Conclusion: False acetabulum has a significant impact on the morphology of the proximal femur and medullary cavity in patients with Crowe type Ⅳ DDH, and the application of three-dimensional reconstruction technique can accurately evaluate the femoral morphology and guide the selection of femoral prosthesis.

Macrophage-targeting bioactive glass nanoparticles for the treatment of intracellular infection and subcutaneous abscess.

Staphylococcus aureus (S. aureus) can survive phagocytosis and gain shelter from macrophages in some cases, and the clinical treatment of the intracellular bacterium also encounters the difficulty of traditional antibiotics in entering mammalian cells. In this work, we use mannose-modified bioactive glass nanoparticles decorated with silver nanoparticles (BGNs-Man/Ag) to treat the S. aureus-induced intracellular infection of macrophages. The results showed that BGNs-Man/Ag could target macrophages, elevate the intracellular ROS levels and drive them toward the M1 phenotype, which was crucial to activate the cell autonomous defence in disposing the intracellular infection. Attractively, BGNs-Man/Ag exhibited higher intracellular bacterial killing efficiency than free vancomycin. For the in vivo treatment of subcutaneous abscess, BGNs-Man/Ag significantly increased the population of M1 macrophages at the early stages of the infection site, resulting in enhanced bactericidal activity and improved regeneration of skin tissues. In short, BGNs-Man/Ag can be a promising antibacterial material in treating the S. aureus-induced intracellular infection of macrophages and subcutaneous abscesses.

Robust Near-Infrared-Responsive Composite Hydrogel Actuator Using Fe3+/Tannic Acid as the Photothermal Transducer.

Light-driven hydrogel actuators show potential applications because their spatiotemporal precision and contact-free manner, especially for near-infrared light (NIR), can be focused on a specific area, which possesses tunable intensity and strong penetrability. Herein, we propose a novel NIR-responsive hydrogel actuator incorporating Fe3+/tannic acid (Fe3+/TA) as a photothermal transducer into the poly(N-isopropylacrylamide) (PNIPAAm) hydrogel via photo-cross-linking and subsequent immersion in FeCl3 solution. TA contains abundant pyrogallol and catechol groups, which can be linked to PNIPAAm through hydrogen bonds during in situ polymerization; moreover, as a mediator, TA can form metal-phenolic networks with Fe3+ via the coordination between catechol and metal ions, endowing the PNIPAAm gel with enhanced mechanical properties as well as NIR-responsive photothermal effect. We demonstrated that introduction of Fe3+/TA maintained the volume phase transition temperature of the hydrogel around 32 °C and guaranteed its deformation behaviors upon NIR irradiation. Furthermore, a higher concentration level of BIS and Fe3+ were verified to facilitate a stronger photothermal capacity of the hydrogels. Therefore, under NIR irradiation, Fe3+/TA within the hydrogel converted NIR light into heat, and the local high temperature in the irradiated region would cause the petals of the "snowflake"-shaped hydrogel to bend upward perpendicular to the horizontal plane within 1 min, possessing excellent repeatability. This study puts forward a new idea of preparing NIR-responsive hydrogel actuators based on Fe3+/TA, which show promising application in the fields of biomimetic devices, flowing control, and soft robotics.

Matrix stiffness-regulated cellular functions under different dimensionalities.

Various cues from the microenvironment in which cells live can regulate cellular functions. In addition to biochemical cues, increasing evidence has demonstrated that mechanical cues (namely, substrate/matrix stiffness in this review) presented by the cell microenvironment are also critically important in regulating cellular functions. However, most studies on stiffness-regulated cellular functions mainly focus on 2D conditions, which might not be able to recapitulate the 3D microenvironment encountered by the cells in vivo. In contrast to the observations in 2D microenvironments, studies have already shown that cells respond differently to mechanical cues under 3D microenvironments. In this review, the mechanisms of cellular mechanosensing and mechanotransduction are briefly presented, followed by the introduction of the most studied 2D/3D platforms. The effects of substrate/matrix stiffness on cellular functions, including cell migration, spreading, proliferation, phenotype, and differentiation, under different dimensionalities are summarized and discussed. Finally, the persisting questions and future outlook are also proposed.

Fast responsive photo-switchable dual-color fluorescent cyclodextrin nanogels for cancer cell imaging.

Photo-switchable dual-color fluorescent nanogels were fabricated via nanoprecipitation in aqueous solution. The spiropyran-modified ß-cyclodextrin (ß-CD-SP) and 4-amino-7-nitro-1,2,3-benzoxadiazole (NBDNH2) were encapsulated into nanogels in the presence of 1,6-hexamethylene diisocyanate (HMDI). In the nanogels, spiropyran moiety acted as fluorescence molecule acceptors under the irradiation of UV or visible light to quench or recover the fluorescence of the NBDNH2 to achieve reversible dual-color fluorescence. The feed ratio of the two fluorophores played vital role on the energy transfer efficiency (E) of the nanogels, and the results showed that high E (90.7%) can be achieved when the feed ratio of NBDNH2/ß-CD-SP is 1:2 (mol/mol). In addition, the nanogels can maintain good photo-switchable fluorescent behavior as long as 5 weeks. With rapid photo-responsiveness (within 60 s), good reversibility, long-term stability, and excellent cytocompatibility, the as-prepared nanogels have been successfully applied to photo-switchable dual-color fluorescent imaging in cancer cell.

A photo-switchable and thermal-enhanced fluorescent hydrogel prepared from N-isopropylacrylamide with water-soluble spiropyran derivative.

Herein, a photo-switchable and thermal-enhanced fluorescent hydrogel has been fabricated from N-isopropylacrylamide (NIPAAm) with a mixture of water-soluble acryloyl-α-cyclodextrin/acryloyl-α-cyclodextrin-spiropyran (acryloyl-α-CD/ acryloyl-α-CD-SP) as cross-linkers. The physical properties, photochromic properties, and fluorescent behavior of the hydrogel were characterized. The fluorescence emission of the hydrogel can be reversibly switched 'on/off' by UV/visible light irradiation, and meanwhile the fluorescence intensity can be enhanced by increasing the temperature above the volume phase transition temperature (VPTT) of the hydrogel. The hydrogel also shows spatiotemporal fluorescent behavior, excellent cytocompatibility, and fatigue resistance in photochromic and photo-switchable fluorescent behaviors.

Preparation and mineralization of a biocompatible double network hydrogel.

Double network (DN) hydrogels have shown favorable toughness and strength and been harnessed as scaffolding materials in tissue engineering, particularly, mineralized DN hydrogels may be potential scaffolds in bone tissue engineering. In this paper, DN hydrogels were fabricated from poly(ethylene glycol) diacrylate (PEGDA) and methacrylated poly(γ-glutamic acid) (mPGA). This DN hydrogel not only showed excellent mechanical properties but also good cytocompatibility as evidenced by the characterizations in terms of swelling ratio, mechanical strength/modulus, and cytotoxicity. Further, the DN hydrogels were subjected to mineralization in simulated body fluid, during which hydroxyapatite or analogues formed within the DN hydrogels; the DN hydrogels may be potentially harnessed as bone tissue engineering scaffold.

Near-infrared Light Responsive Polymeric Nanocomposites for Cancer Therapy.

Inorganic nanoparticles, which can absorb and convert near infrared (NIR) light to heat to ablate cancer cells, have been widely investigated in photothermal therapy. However, the inherent poor solubility and acute systemic toxicity of these inorganic particles hinder their application in clinical practice. Polymeric nanocomposites materials containing both inorganic nanoparticles and polymers could be harnessed to achieve enhanced photothermal therapeutic effect as well as improved biocompatibility and multi-responsiveness. Synergistic chemo-photothermal efficacy towards cancer cells and tumor tissue can thus be realized through such multi-functional and multi-responsive polymeric nanocomposites. In this review, the recent developments in polymeric nanocomposites based on different types of inorganic nanoparticles (i.e. gold, carbon nanotube, graphene, and upconversion nanoparticles) for NIR-triggered cancer therapy are summarized.

Preparation of a novel antibacterial chitosan-poly(ethylene glycol) cryogel/silver nanoparticles composites.

Cryogel was synthesized through cryogelation of methacrylated carboxymethyl chitosan (mCMC) and poly(ethylene glycol) diacrylate (PEGDA) precursors by photopolymerization. Due to its excellent properties, such as fast swelling behavior, inter-connective porous structure, high water absorbing capacity, especially the presence of abundant carboxylmethyl groups on its backbone, the cryogel not only favored the absorption of silver ions but also was proved to be a good matrix for the incorporation of silver nanoparticles (AgNPs) by in situ chemical reduction. The structure, morphology, and swelling behavior of the cryogel and cryogel/AgNPs composite were characterized. And the results of inhibition zone test and antibacterial inhibition ratio indicated the cryogel/AgNPs composite exhibited prominent and durable antibacterial activity against Gram-negative E. coli and could be utilized as potential antibacterial materials.

Nanocomposite Hydrogels and Their Applications in Drug Delivery and Tissue Engineering.

Traditional hydrogels usually possess inferior mechanical properties as well as lacking multi-functionalities. Nano-sized particles/fillers, both inorganic and organic materials, have unique chemical, physical, and biological functions, and have been extensively studied as biomaterials or bio-functional materials. Nanocomposite hydrogels, which combine the advantages of both nano-fillers and hydrogel matrices, may result in improved mechanical and biological properties and find their potential applications in biomedical field. This paper reviews recent developments in the synthesis, preparation, and characterization of nanocomposite hydrogels; their biomedical applications, such as drug delivery matrices and tissue engineering scaffolding materials are also summarized.

Enzymatically cross-linked hyaluronic acid/graphene oxide nanocomposite hydrogel with pH-responsive release.

Hyaluronic acid (HA) is made up of repeating disaccharide units (ß-1,4-d-glucuronic acid and ß-1,3-N-acetyl-d-glucosamine) and is a major constituent of the extracellular matrix. HA and its derivatives which possess excellent biocompatibility and physiochemical properties have been studied in drug delivery and tissue engineering applications. Tyramine-based HA hydrogel with good compatibility to cell and tissue has been reported recently. However, inferior mechanical property may limit the biomedical application of the HA hydrogel. In this study, HA/graphene oxide (GO) nanocomposite (NC) hydrogel was prepared through a horseradish peroxidase catalyzed in situ cross-linking process. As compared with pure HA hydrogels, incorporation of GO to the HA matrix could significantly enhance the mechanical properties (storage moduli 1800 Pa) of the hydrogel and prolong the release of rhodamine B (RB) as the model drug from the hydrogel (33 h) as well. In addition, due to the multiple interactions between GO and RB, the NC hydrogels showed excellent pH-responsive release behavior. The release of RB from the NC hydrogel was prolonged at low pH (pH 4.0) in the presence of GO, which could be attributed to the enhanced interactions between GO and HA as well as with RB. In situ three-dimensional encapsulation of mouse embryonic fibroblasts (BALB 3T3 cells) in the NC hydrogels and cytotoxicity results indicated the cytocompatibility of both the enzymatic cross-linking process and HA/GO NC hydrogels (cell viability 90.6 ± 4.25%). The enzymatically catalyzed fabrication of NC hydrogels proved to be an easy and mild approach, and had great potential in the construction of both tissue engineering scaffolds and stimuli-responsive drug release matrices.

Preparation and characterization of double macromolecular network (DMMN) hydrogels based on hyaluronan and high molecular weight poly(ethylene glycol).

Abundant research efforts have been devoted to meet the demands for high-strength hydrogels in biomedical applications. Double-network (DN) hydrogels and homogeneous hydrogels are two typical samples. In this study, a novel ultra-strong and resilient double macromolecular network (DMMN) hydrogel system has been developed via a two-step sequential cross-linking process using hyaluronan (HA) and high molecular weight poly(ethylene glycol) (PEG) for the first and second network, respectively. A lower concentration of the HA precursor solution and a higher concentration of the PEG precursor solution as well as a higher molecular weight of the PEG precursor are beneficial to produce high-strength DMMN gels. Dynamic light scattering measurements demonstrate that DMMN gels possess the more evenly distributed polymer networks; the distinctive double and relatively evenly distributed networks of the DMMN gel make it combine the current DN and homogeneous network strategies for preparing robust hydrogels. The optimized DMMN gel is capable of sustaining up to 50 MPa of compressive stress. Besides, DMMN gels exhibit excellent cytocompatibility. This study expands the DN principle in designing and fabricating high-strength hydrogels with biocompatible macromolecules that show a promising prospect for biomedical applications.