Magnesium Oxide-Assisted Dual-Cross-Linking Bio-Multifunctional Hydrogels for Wound Repair during Full-Thickness Skin Injuries

Full-thickness skin injuries have always been an intricate problem in clinical treatment. The application of biomaterials provides an artificial matrix for the recruitment of cells and deposition of extracellular matrix to accelerate wound healing. For the recovery of full-thickness skin defects, the double cross-linking of MgO-catechol and Schiff's base bonds are used as part of the gel-forming mechanism, and a bio-multifunctional hydrogel (CCOD-MgO) is prepared by adding MgO to catechol-modified chitosan (CHI-C) and oxidized dextran (ODex). The CCOD-MgO demonstrates high tissue adhesion, excellent self-repairing, hemostasis function, and low swelling rate. With the addition of MgO and catechol chelation, the adhesion strength of CCOD-MgO is about 35 kpa, which is much greater than fibrin glue. Moreover, the CCOD-MgO has better antibacterial properties than CHI-C/ODex hydrogel (CCOD) due to the synergy of chitosan and MgO in vitro. Accordingly, the CCOD-MgO can protect the wounds from infection and accelerate the healing speed of the epidermis in full-thickness cutaneous defect and burn model in vivo. These results demonstrate that the CCOD-MgO would be a promising therapeutic strategy in full-thickness skin injuries for clinical therapies.     

3D Printing Hydrogel Scaffolds with Nanohydroxyapatite Gradient to Effectively Repair Osteochondral Defects in Rats

Osteochondral (OC) defects pose an enormous challenge with no entirely satisfactory repair strategy to date. Herein, a 3D printed gradient hydrogel scaffold with a similar structure to that of OC tissue is designed, involving a pure hydrogel-based top cartilage layer, an intermediate layer for calcified cartilage with 40% (w w⁻¹) nanohydroxyapatite (nHA) and 60% (w w⁻¹) hydrogel, and a 70/30% (w w⁻¹) nHA/hydrogel-based bottom subchondral bone layer. This study is conducted to evaluate the efficacy of the scaffold with nHA gradients in terms of its ability to promote OC defect repair. The fabricated composites are evaluated for physicochemical, mechanical, and biological properties, and then implanted into the OC defects in 56 rats. Overall, bone marrow stromal cells (BMSCs)-loaded gradient scaffolds exhibit superior repair results as compared to other scaffolds based on gross examination, micro-computed tomography (micro-CT), as well as histologic and immunohistochemical analyses, confirming the ability of this novel OC graft to facilitate simultaneous regeneration of cartilage-subchondral bone.     

Injectable Self-Healing Natural Biopolymer-Based Hydrogel Adhesive with Thermoresponsive Reversible Adhesion for Minimally Invasive Surgery

Biocompatible hydrogel adhesives with multifunctional properties, including injectability, fast self-healing, and suitable on-demand detachment, are highly desired for minimally invasive procedures, but such materials are still lacking. Herein, an injectable self-healing biocompatible hydrogel adhesive with thermoresponsive reversible adhesion based on two extracellular matrix-derived biopolymers, gelatin and chondroitin sulfate, is developed to be used as a surgical adhesive for sealing or reconnecting ruptured tissues. The resulting hydrogels present good self-healing and can be conveniently injected through needles. The strong tissue adhesion at physiological temperatures originates from the Schiff base and hydrogen bonding interactions between the hydrogel and tissue that can be weakened at low temperatures, thereby easily detaching the hydrogel from the tissue in the gelation state. In vivo and ex vivo rat model show that the adhesives can effectively seal bleeding wounds and fluid leakages in the absence of sutures or staples. Specifically, a proof of concept experiment in a damaged rat liver model demonstrates the ability of the adhesives to act as a suitable laparoscopic sealant for laparoscopic surgery. Overall, the adhesive has several advantages, including low cost and ease of production and application that make it an exceptional multifunctional tissue adhesive/sealant, effective in minimally invasive surgical applications.     

Bioinspired Highly Anisotropic,Ultrastrong and Stiff,and Osteoconductive Mineralized Wood Hydrogel Composites for Bone Repair

Anisotropic hydrogels mimicking the biological tissues with directional functions play essential roles in damage-tolerance, cell guidance and mass transport. However, conventional synthetic hydrogels often have an isotropic network structure, insufficient mechanical properties and lack of osteoconductivity, which greatly limit their applications for bone repair. Herein, inspired by natural bone and wood, a biomimetic strategy is presented to fabricate highly anisotropic, ultrastrong and stiff, and osteoconductive hydrogel composites via impregnation of biocompatible hydrogels into the delignified wood followed by in situ mineralization of hydroxyapatite (HAp) nanocrystals. The well-aligned cellulose nanofibrils endow the composites with highly anisotropic structural and mechanical properties. The strong intermolecular bonds of the aligned cellulose fibrils and hydrogel/wood interaction, and the reinforcing nanofillers of HAp enable the composites remarkable tensile strength of 67.8 MPa and elastic modulus of 670 MPa, three orders of magnitude higher than those of conventional alginate hydrogels. More importantly, the biocompatible hydrogel together with aligned HAp nanocrystals could effectively promote osteogenic differentiation in vitro and induce bone formation in vivo. The bone ingrowth into the hydrogel composite scaffold also yields good osteointegration. This study provides a low-cost, eco-friendly, feasible, and scalable approach for fabricating anisotropic, strong, stiff, hydrophilic, and osteoconductive hydrogel composites for bone repair.     

Hernia Mesh with Biomechanical and Mesh–Tissue Interface Dual Compliance for Scarless Abdominal Wall Reconstruction

A fabric hydrogel composite hernia mesh with biomechanical and mesh–tissue interface dual compliance is designed for scarless abdominal wall reconstruction. The mesh is composed of a polyester knitted fabric and chitosan–polyacrylamide hydrogel complex. The mechanical properties of the composite mesh are adjusted to resemble the human abdominal wall by alkali treatment of chitosan to achieve good biomechanical compliance. An adhesion group is introduced into the composite mesh that forms covalent bonds with tissue, eliminating the need for suturing, reducing stress concentration at the fixation site, achieving mesh-tissue interface compliance, and improving the simplicity of the operation. Covalent bonds and hydrogen bonds make the mesh have strong adhesion (70.1 ± 3.2 kPa) and repeatable (four times) robust adhesiveness. In vivo experiments using a rabbit abdominal wall defect model demonstrate quick adhesiveness and excellent functional reconstruction. Biomechanical and mesh–tissue interface dual compliance allow the tissue to regenerate an intact abdominal wall structure. The adhesive fabric hydrogel composite hernia mesh offers significant clinical values for repairing abdominal wall defects and provides design ideas for repairing other load-bearing soft tissues.     

Doxorubicin‐Loaded Single Wall Nanotube Thermo‐Sensitive Hydrogel for Gastric Cancer Chemo‐Photothermal Therapy

Single wall carbon nanotube (SWNT) based thermo‐sensitive hydrogel (SWNT‐GEL) is reported, which provides an injectable drug delivery system as well as a medium for photothermal transduction. SWNT‐hydrogel alone appears to be nontoxic on gastric cancer cells (BGC‐823 cell line) but leads to cell death with NIR radiation through a hyperthermia proapoptosis mechanism. By incorporating hyperthermia therapy and controlled in situ doxorubicin (DOX) release, DOX‐loaded SWNT‐hydrogel with NIR radiation proves higher tumor suppression rate on mice xenograft gastric tumor models compared to free DOX without detectable organ toxicity. The developed system demonstrates improved efficacy of chemotherapeutic drugs which overcomes systemic adverse reactions and presents immense potential for gastric cancer treatment.     

Digital Plasmonic Patterning for Localized Tuning of Hydrogel Stiffness

The mechanical properties of the extracellular matrix (ECM) can dictate cell fate in biological systems. In tissue engineering, varying the stiffness of hydrogels—water‐swollen polymeric networks that act as ECM substrates—has previously been demonstrated to control cell migration, proliferation, and differentiation. Here, “digital plasmonic patterning” (DPP) is developed to mechanically alter a hydrogel encapsulated with gold nanorods using a near‐infrared laser, according to a digital (computer‐generated) pattern. DPP can provide orders of magnitude changes in stiffness, and can be tuned by laser intensity and speed of writing. In vitro cellular experiments using A7R5 smooth muscle cells confirm cell migration and alignment according to these patterns, making DPP a useful technique for mechanically patterning hydrogels for various biomedical applications.     

TFT—LCDs的缺陷检测和修补技术

概述了 TFT-LCDs 的缺陷分类、成因以及各种 TFT-LCDs 无缺陷技术,着重阐述了 TFT 矩阵板的一种电气缺陷检测原理和确定缺陷类型及位置的方法;介绍了各种缺陷的激光修补技术。     

A Mineralized High Strength and Tough Hydrogel for Skull Bone Regeneration

Over the past decade, high strength hydrogels have been intensively investigated. However, developing high strength biofunctional hydrogels for eliciting bone regeneration has been rarely reported. In this work, a mineralized high strength and tough hydrogel is synthesized by one‐step copolymerization of acrylonitrile, 1‐vinylimidazole, and polyethylene glycol diacrylate, followed by in situ precipitation mineralization. It is demonstrated that the CN? CN dipole–dipole pairings combined with the interaction of CaP nanocrystals with polymer chains contribute to tremendous increase of tensile/compressive strength, modulus, and fracture energy up to 6.1 MPa, 11.5 MPa, 6.47 MPa, and 7935 J m^?2, respectively. The biomineralization is shown to facilitate the attachment and proliferation of C2C12 cells in vitro. This biomineralized hydrogel scaffold is implanted into an 8 mm diameter critical‐size of calvarial defect of rats to evaluate the bone regeneration. 12 week postsurgery results reveal that the mineralized hydrogel exhibits the highest bone volume and density within the defect as measured by computed tomography and histology. This mineralized high strength and tough hydrogel offers a broad range of possibilities to be developed as biofunctional scaffold to promote the reconstruction and regeneration of not only bone, but also load‐bearing connective tissue.     

Micropatterned Protein for Cell Adhesion through Phototriggered Charge Change in a Polyvinylpyrrolidone Hydrogel

Regulated immobilization of proteins on hydrogels allows for the creation of highly controlled microenvironments to meet the special requirements of cell biology and tissue engineering devices. Light is an ideal stimulus to regulate immobilization because it can be controlled in time, space, and intensity. Here, a photoresponsive hydrogel that enables the patterning of proteins by a combination of electrostatic adsorption and photoregulated charge change on a hydrogel is developed. It is based on a photosensitive cationic monomer ( CLA ), a coumarin caged lysine betaine zwitterion, incorporated into a polyvinylpyrrolidone ( PVP ) hydrogel, which can controllably change the charge from an adhesive positive state to an anti‐adhesive zwitterion state upon irradiation at 365 nm. With this strategy, the immobilization of proteins is regulated and cell adhesion is programmed on hydrogels on demand. This approach should open up new avenues for hydrogels in biomedical applications.     

A Single Component Conducting Polymer Hydrogel as a Scaffold for Tissue Engineering

Conducting polymers (CPs) have exciting potential as scaffolds for tissue engineering, typically applied in regenerative medicine applications. In particular, the electrical properties of CPs has been shown to enhance nerve and muscle cell growth and regeneration. Hydrogels are particularly suitable candidates as scaffolds for tissue engineering because of their hydrated nature, their biocompatibility, and their tissue‐like mechanical properties. This study reports the development of the first single component CP hydrogel that is shown to combine both electro‐properties and hydrogel characteristics. Poly(3‐thiopheneacetic acid) hydrogels were fabricated by covalently crosslinking the polymer with 1,1′‐carbonyldiimidazole (CDI). Their swelling behavior was assessed and shown to display remarkable swelling capabilities (swelling ratios up to 850%). The mechanical properties of the networks were characterized as a function of the crosslinking density and were found to be comparable to those of muscle tissue. Hydrogels were found to be electroactive and conductive at physiological pH. Fibroblast and myoblast cells cultured on the hydrogel substrates were shown to adhere and proliferate. This is the first time that the potential of a single component CP hydrogel has been demonstrated for cell growth, opening the way for the development of new tissue engineering scaffolds.     

Charge-Driven Self-Assembled Microspheres Hydrogel Scaffolds for Combined Drug Delivery and Photothermal Therapy of Diabetic Wounds

The treatment of diabetic wound remains a big clinical challenge. Hydrogel that can provide physical barrier and humidity displays amazing potentials for managing the diabetic wounds healing. Herein, a new charge-driven self-assembled microsphere hydrogel scaffold (SMHS) is reported based on an electric charge interaction, by combining use of black phosphorus (BP)-contained chitosan methacryloyl (CS) microspheres with positive charge and basic fibroblast growth factor-contained hyaluronic acid methacryloyl (HA) microspheres with negative charge. The weak charge attraction among microspheres gives the SMHS the injectable characteristic. Due to the existence of BP, near-infrared (NIR) irradiation has obvious effects on the degradation and drug release behaviors of SMHS. Significantly, SMHS that combines the short-term physical (photothermal) intervention and long-term chemical (drug release) intervention may be promising in spatio-temporal regulation of regenerative microenvironment. SMHS with NIR irradiation (SMHS+NIR) can promote cell proliferation, cell migration, angiogenesis and macrophage polarization. Moreover, in diabetic rat skin wounds, SMHS+NIR significantly accelerates the wound healing process by simultaneously inhibiting the inflammatory response, promoting angiogenesis and tissues remodeling. The outcome of this research not only provides a biomaterial for diabetic wounds healing, but also demonstrates a new strategy for designing novel hydrogel-based biomaterials which have the free editing and combination functions.     

Radiopaque Highly Stiff and Tough Shape Memory Hydrogel Microcoils for Permanent Embolization of Arteries

Transcatheter arterial embolization of aneurysm with metal microcoils is notoriously prone to recanalization arising from the low filling ratio due to their extreme rigidity. Smart hydrogel microcoils with tunable modulus may essentially significantly improve the therapeutic efficacy. Here, a radiopaque highly stiff body‐temperature‐triggered shape memory (SM) hydrogel is fabricated for the first time by introducing reversible hydrophobic dipole pairing microdomains in the flexibly crosslinked network, followed by BaSO₄ precipitation. This radiopacification does not affect their mechanical performances as well as the SM effect. It is demonstrated that the mechanical properties of SM hydrogels are comparable to those of rubbers and can be modulated by adjusting temperature ranging from 20 to 40 °C. Benefiting from the thermoresponsive mechanical properties, the stiff radiopaque hydrogel strip can easily pass through a catheter under the protection of cool saline for delivery into pig's renal artery, and spontaneously and rapidly transformed into a microcoil upon contacting blood. Real‐time angiogram reveals that continuous delivery of several hydrogel microcoils can efficiently occlude the blood supply. The kidneys are atrophied considerably over three month postoperative follow‐up, and no recanalization occurs throughout the experimental time. These novel hydrogel microcoils are promising to be developed as novel permanent embolic agents for treating aneurysm.     

Injection of ROS-Responsive Hydrogel Loaded with Basic Fibroblast Growth Factor into the Pericardial Cavity for Heart Repair

Myocardial infarction, among other ischemic heart diseases, is the major cause of mortality and morbidity for patients who have heart diseases. Timely reperfusion of the ischemic myocardium is the most effective way to treat myocardial infarction. However, blood reperfusion to the ischemic tissues leads to an overproduction of toxic reactive oxygen species (ROS), which can further exacerbate myocardial damage on top of ischemic injury. ROS has been used as a diagnostic marker and therapeutic target for ischemia-reperfusion (I/R) injury and as an environmental stimulus to trigger drug release. In this study, a ROS-sensitive cross-linked poly(vinyl alcohol) (PVA) hydrogel is synthesized to deliver basic fibroblast growth factor (bFGF) for myocardial repair. The therapeutic gel is injected into the pericardial cavity. Upon delivery, the hydrogel spread on the surface of the heart and form an epicardiac patch in situ. In a rat model of I/R injury, bFGF released from the gel could penetrate the myocardium. Such intervention protects cardiac function and reduces fibrosis in the post-I/R heart, with enhanced angiomyogenesis. Furthermore, the safety and feasibility of minimally invasive injection and access into the pericardial cavity in both pigs and human patients are demonstrated.     

Tissue Adhesive Catechol‐Modified Hyaluronic Acid Hydrogel for Effective,Minimally Invasive Cell Therapy

Current hyaluronic acid (HA) hydrogel systems often cause cytotoxicity to encapsulated cells and lack the adhesive property required for effective localization of transplanted cells in vivo. In addition, the injection of hydrogel into certain organs (e.g., liver, heart) induces tissue damage and hemorrhage. In this study, we describe a bioinspired, tissue‐adhesive hydrogel that overcomes the limitations of current HA hydrogels through its improved biocompatibility and potential for minimally invasive cell transplantation. HA functionalized with an adhesive catecholamine motif of mussel foot protein forms HA‐catechol (HA‐CA) hydrogel via oxidative crosslinking. HA‐CA hydrogel increases viability, reduces apoptosis, and enhances the function of two types of cells (human adipose‐derived stem cells and hepatocytes) compared with a typical HA hydrogel crosslinked by photopolymerization. Due to the strong tissue adhesiveness of the HA‐CA hydrogel, cells are easily and efficiently transplanted onto various tissues (e.g., liver and heart) without the need for injection. Stem cell therapy using the HA‐CA hydrogel increases angiogenesis in vivo, leading to improved treatment of ischemic diseases. HA‐CA hydrogel also improved hepatic functions of transplanted hepatocytes in vivo. Thus, this bioinspired, tissue‐adhesive HA hydrogel can enhance the efficacy of minimally invasive cell therapy.     

A Universal and Facile Approach for the Formation of a Protein Hydrogel for 3D Cell Encapsulation

A universal and facile approach to modifying proteins so that they can rapidly form hydrogel upon mixing with crosslinkers is presented. The concept of it is to introduce maleimide, which is highly reactive with dithiol‐containing crosslinkers via thiol‐ene click chemistry, onto proteins. Bovine serum albumin (BSA) is used as a model protein due to its good stability and low cost. The results here show that a protein hydrogel can be readily formed by blending modified BSA and resilin‐related peptide crosslinker solutions at a proper ratio. The hydrogel exhibits good elasticity and tunable mechanical as well as biochemical properties. Moreover, it allows convenient 3D cell encapsulation and shows good biocompatibility. Muscle cells embedded in the hydrogel are promoted to spread by incorporating arginyl‐glycyl‐aspartic acid (RGD)‐containing peptide into the system, thus warranting a bright future of it in regenerative medicine.     

Injectable Hydrogel with NIR Light-Responsive,Dual-Mode PTH Release for Osteoregeneration in Osteoporosis

Effective treatments to overcome osteoblast/osteoclast imbalance are the key to achieving desirable bone regeneration for osteoporosis patients. When used for local bone repair, parathyroid hormone (PTH) often leads to either excessive osteoclasts under continuous exposure or insufficient osteoclasts with pulsatile release of PTH. Herein, an injectable multifunctional in situ-generated calcium phosphate nanoparticle (ICPN)-coordinated poly(dimethylaminoethyl methacrylate-co-2-hydroxyethyl methacrylate) (DHCP) hydrogel loaded with PTH for near-infrared (NIR)-stimulated release is developed to achieve bone regeneration in an ovariectomized (OVX) model. Photothermal-responsive poly(N-acryloyl glycinamide-co-acrylamide) PNAm-indocyanine green ICG-PTH microspheres (PIP MSs) endow a dual-mode release system with a sustained release at low concentrations, a pulse release of PTH, and in situ pore formation properties. The PIP MS-encapsulated DHCP hydrogel (DHCP-10PIP/d) is injected into the bone defects of OVX rats. Under NIR irradiation, the localized photothermal effects trigger on-demand PTH release and in situ micropores formation through the gel–sol transition of PIP MSs, and the repeated treatment is harmless to the bioactivity of PTH. This platform can enhance osteoblast and osteoclast activity at the same time both in vitro and in vivo and repair the cranial defects of OVX rats successfully. Overall, this work provides a promising strategy for PTH delivery to repair osteoporotic bone defects.     

A Protein-Adsorbent Hydrogel with Tunable Stiffness for Tissue Culture Demonstrates Matrix-Dependent Stiffness Responses

Although tissue culture plastic has been widely employed for cell culture, the rigidity of plastic is not physiologic. Softer hydrogels used to culture cells have not been widely adopted in part because coupling chemistries are required to covalently capture extracellular matrix (ECM) proteins and support cell adhesion. To create an in vitro system with tunable stiffnesses that readily adsorbs ECM proteins for cell culture, a novel hydrophobic hydrogel system is presented via chemically converting hydroxyl residues on the dextran backbone to methacrylate groups, thereby transforming non-protein adhesive, hydrophilic dextran to highly protein adsorbent substrates. Increasing methacrylate functionality increases the hydrophobicity in the resulting hydrogels and enhances ECM protein adsorption without additional chemical reactions. These hydrophobic hydrogels permit facile and tunable modulation of substrate stiffness independent of hydrophobicity or ECM coatings. Using this approach, it is shown that substrate stiffness and ECM adsorption work together to affect cell morphology and proliferation, but the strengths of these effects vary in different cell types. Furthermore, it is revealed that stiffness-mediated differentiation of dermal fibroblasts into myofibroblasts is modulated by the substrate ECM. The material system demonstrates remarkable simplicity and flexibility to tune ECM coatings and substrate stiffness and study their effects on cell function.     

均压环螺栓补装工具的研制

均压环是改善绝缘子串电压分布的环状金具。装在均压环上的螺栓,受大风天气及高压输电线路来回摆动的影响,时间久了会造成螺栓的脱落,从而影响线路的使用。为了解决带电作业情况下远距离安装均压环上脱落的螺栓或螺母,设计研制了均压环螺栓补装工具。通过现场应用发现,研制的工具设计合理,结构紧凑,使用方便。