Irregular Defects Research Articles

Silver Nanowire Reinforced Conductive and Injectable Colloidal Gel for Effective Wound Healing Via Electrical Stimulation.

The remarkable biocapacity, injectability, and adaptability of colloidal gels lead to their widespread use in tissue engineering as irregular defect implants. However, multifunctionalities including electroconductivity and antibacterial property are highly required for colloidal gels. In addition, the inherently weak mechanical property of physically crosslinked colloidal gels limits their application. Herein, Ag nanowires (Ag NWs)-reinforced colloidal gels composed of biocompatible gelatin nanoparticles and polydopamine-modified Ag NWs through the controlled electrostatic assembly, which are injectable and conductive, are presented. 1D Ag NWs can significantly improve the mechanical and electrical properties of the colloidal gel while maintaining its inherent excellent injectability. Owing to the network of Ag NWs, the storage modulus and conductivity of the optimized Ag NW colloidal gel are 7.5 and 13 times higher, respectively, than those of the colloidal gel made up of polydopamine-modified Ag nanoparticles with equivalent Ag concentration. Further, this Ag NW colloidal gel can adapt to sharp wounds on skin, which accelerates the healing of an MRSA-infected wound via electrical stimulation.

Chitosan and hyaluronic acid based injectable dual network hydrogels - Mediating antimicrobial and inflammatory modulation to promote healing of infected bone defects

In bone defects, infections lead to excessive inflammation, increased bacterial, and bone lysis, resulting in irregular wounds that hinder new bone regeneration. Injectable bioactive materials with adequate antimicrobial activity and strong osteogenic potential are urgently required to remedy irregular defects, eradicate bacteria, and facilitate the generation of new bone tissue. In this research, injectable dual-network composite hydrogels consisting of sulfated chitosan, oxidized hyaluronic acid, β-sodium glycerophosphate, and CuSr doped mesoporous bioactive glass loaded with bone morphogenetic protein (CuSrMBGBMP-2) were utilized for the first time to treat infectious bone defects. Initially, the hydrogel was injected into the wound at 37 °C with minimal invasion to establish a stable state and prevent hydrogel loss. Subsequently, sulfated chitosan eliminated bacteria at the wound site and facilitated cell proliferation with oxidized hyaluronic acid. Additionally, CuSrMBGBMP-2 strengthened antibacterial properties, regulated inflammatory reactions, promoted angiogenesis and osteogenic differentiation, addressing the deficiency in late-stage osteogenesis. Specifically, the injectable dual-network hydrogel based on chitosan and hyaluronic acid is minimally invasive, offering antibacterial, anti-inflammatory, pro-angiogenic, and bone regeneration properties. Therefore, this hydrogel with injectable dual network properties holds great promise for the treatment of bone infections in the future.

Surface Crystal and Degradability of Shape Memory Scaffold Essentialize Osteochondral Regeneration.

The minimally invasive deployment of scaffolds is a key safety factor for the regeneration of cartilage and bone defects. Osteogenesis relies primarily on cell-matrix interactions, whereas chondrogenesis relies on cell-cell aggregation. Bone matrix expansion requires osteoconductive scaffold degradation. However, chondrogenic cell aggregation is promoted on the repellent scaffold surface, and minimal scaffold degradation supports the avascular nature of cartilage regeneration. Here, a material satisfying these requirements for osteochondral regeneration is developed by integrating osteoconductive hydroxyapatite (HAp) with a chondroconductive shape memory polymer (SMP). The shape memory function-derived fixity and recovery of the scaffold enabled minimally invasive deployment and expansion to fill irregular defects. The crystalline phases on the SMP surface inhibited cell aggregation by suppressing water penetration and subsequent protein adsorption. However, HAp conjugation SMP (H-SMP) enhanced surface roughness and consequent cell-matrix interactions by limiting cell aggregation using crystal peaks. After mouse subcutaneous implantation, hydrolytic H-SMP accelerated scaffold degradation compared to that by the minimal degradation observed for SMP alone for two months. H-SMP and SMP are found to promote osteogenesis and chondrogenesis, respectively, in vitro and in vivo, including the regeneration of rat osteochondral defects using the binary scaffold form, suggesting that this material is promising for osteochondral regeneration.

Defect detection of printed circuit board based on adaptive key-points localization network

Many deep neural networks (DNNs) have been applied in the defect detection of products. Due to the irregular and small defects on printed circuit boards (PCB), it is difficult for the DNN-based defect detection models to achieve good detection performance. In this paper, a new DNN, adaptive key point localization network (AKPLNet) is proposed for PCB defect detection. Firstly, residual pyramid heat mapping network (RFHNet) that is composed of ResNet50_FPN and thermodynamic mechanism (TM), is used to perform multi-scale feature extraction and defect location. Secondly, an adaptive tree structure region proposal network (AT-RPN) based on tree structure Parzen estimation is proposed to obtain the predicted regions of the target, which reduces the need for large number of priori knowledge during the detection process. Finally, a key point regression algorithm is proposed to locate defects accurately. The defect detection performance of AKPLNet is validated on two PCB datasets. The mean average precision (mAP) of AKPLNet reaches 96.9% and 99.0% on PCB-Master dataset with the color images and DeepPCB-Master dataset with the grayscale images, improving 2.1% and 2.3% compared with Yolov7, respectively. The testing results demonstrate that AKPLNet achieves the better detection accuracy than those state-of-the-art methods.

Enhancing the biological functionality of poly (lactic‐co‐glycolic acid) cage‐like structures through surface modification with micro‐ and nano‐sized hydroxyapatite particles

AbstractBiomaterials with exceptional performance are crucial for addressing the challenges of complex bone regeneration. Compared with traditional three‐dimensional scaffolds, injectable microspheres enable new strategies for the treatment of irregular bone defects. Biodegradable poly (lactic‐co‐glycolic acid) has found widespread applications as microcarriers of drugs, proteins, and other active macromolecules. Applied to the surface of poly (lactic‐co‐glycolic acid) cage‐like structures (PLGA‐CAS), hydroxyapatite (HA) effectively reduces inflammation while enhancing biological effects. In this study, we loaded the surface of PLGA‐CAS with micro‐ and nano‐hydroxyapatite particles, referred to as μHA/PLGA‐CAS and nHA/PLGA‐CAS, respectively. Subsequently, their material characteristics and biological effects were assessed. The incorporation of hydroxyapatite onto PLGA‐CAS resulted in enhanced surface roughness and hydrophilicity, coupled with improved thermal stability and delayed degradation. Furthermore, μHA/PLGA‐CAS induced osteogenic differentiation of osteoblast precursor cells, while nHA/PLGA‐CAS improved endothelial cell adhesion and stimulated angiogenic differentiation in vitro. Collectively, these findings suggest that μHA/PLGA‐CAS and nHA/PLGA‐CAS, each with distinct characteristics, hold significant potential for application as microcarriers in various biomedical contexts.

Integration of BMP-2/PLGA microspheres with the 3D printed PLGA/CaSO4 scaffold enhances bone regeneration

Treatment of large and complex irregular bone defects is a major clinical challenge in orthopedic surgery. The current treatment includes bone transportation using the Ilizarov technique and bone cement repair using the Masquelet technique, but they require long-term manual intervention or secondary operation. To improve this situation, we compared the different implanting materials in the literature published in the past 10 years, finding that glycolic acid copolymer (PLGA) and Calcium sulfate (CaSO4) are appropriated to be used as synthetic bone materials due to their advantages of easy-availability, nontoxicity, osteogenic properties and rapid degradation. Meanwhile, the development of 3D printing technique and devices makes it relatively easier to synthetize customized bio-mimetic porous scaffolds, thus facilitating the release of modified protein. In this study, we compounded BMP-2/PLGA microspheres with polylactic glycolic acid copolymer/CaSO4 (PC) 3D printed scaffold to improve the osteogenic properties of the scaffold. The result of our in vitro experiment demonstrated that the prepared PCB scaffold not only had satisfactory bio-compatibility, but also promoted osteogenic differentiation. This 3D printed scaffold is capable to accelerate the repair of complex bone defects by promoting new bone formation, suggesting that it may prove to be a potential bone tissue engineering substitute.

Mechanically robust and personalized silk fibroin-magnesium composite scaffolds with water-responsive shape-memory for irregular bone regeneration

The regeneration of critical-size bone defects, especially those with irregular shapes, remains a clinical challenge. Various biomaterials have been developed to enhance bone regeneration, but the limitations on the shape-adaptive capacity, the complexity of clinical operation, and the unsatisfied osteogenic bioactivity have greatly restricted their clinical application. In this work, we construct a mechanically robust, tailorable and water-responsive shape-memory silk fibroin/magnesium (SF/MgO) composite scaffold, which is able to quickly match irregular defects by simple trimming, thus leading to good interface integration. We demonstrate that the SF/MgO scaffold exhibits excellent mechanical stability and structure retention during the degradative process with the potential for supporting ability in defective areas. This scaffold further promotes the proliferation, adhesion and migration of osteoblasts and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. With suitable MgO content, the scaffold exhibits good histocompatibility, low foreign-body reactions (FBRs), significant ectopic mineralisation and angiogenesis. Skull defect experiments on male rats demonstrate that the cell-free SF/MgO scaffold markedly enhances bone regeneration of cranial defects. Taken together, the mechanically robust, personalised and bioactive scaffold with water-responsive shape-memory may be a promising biomaterial for clinical-size and irregular bone defect regeneration.

Individualized design program of multiple flaps for adapting different zones to repair large irregular wounds in children

ObjectiveManagement of large irregular wounds in children had been confusing plastic and reconstructive surgeons. Herein, this study was aimed to propose a new treatment method based on the principle of adapting different recipient zones to overcome the intractable wounds, simplifying and programing the design process of targeted flaps for covering large irregular soft-tissue defects. Patients and methodsFrom January 2009 to December 2020, 31 children (9 girls and 22 boys) aged 3–16 years (mean 9.8 years) underwent multiple modular flaps with edge to edge splicing reconstruction of the lower extremities. All the wounds were large with non-adjacent defects and with or without a dead space. Several variants of flaps were harvested according to the needs and reconstruction requirements of patients. ResultsA total of 71 flaps were harvested from 31 patients and all flaps donor sites received primary closure. Nine patients underwent split-thickness skin grafting, and three cases of flaps survived from vascular crisis by rebuilding the vessels and the rest accepting LD flap transplants. And five partial necrosis of the distal epidermis flaps recovered using skin grafting and dressing change. No major complication was encountered in other patients and donor sites, except one heel ulcer. During the follow-up (ranging from 16 to 38 months, mean 27.7 months), aesthetic and functional results of reconstructed limbs were satisfactory in all patients. ConclusionsThe Individualized design program of multiple flaps for adapting different recipient zones is an alternative for repairing large irregular soft-tissue defects in children, beneficial for plastic and reconstructive surgeons to simplify and program the process of designing and perform multiple flaps to achieve this goal. Level of evidenceIII, Retrospective.

Biomimetic dually cross-linked injectable poly(l-glutamic acid) based nanofiber composite hydrogels with self-healing, osteogenic and angiogenic properties for bone regeneration

Biomimetic hydrogels with satisfactory mechanical properties and osteogenic/angiogenic abilities have attracted extensive attention in recent years. Injectable hydrogels with the advantages of minimally invasive implantation and adaptability to irregular defects exhibit superior application potential in the field of bone regeneration. However, poor mechanical properties and limited self-healing ability hinder their potential as supporting materials. Furthermore, the absence of osteogenic and angiogenic properties significantly affect their application in bone regeneration. For injectable hydrogels, simulating natural bone tissue ECM presents an opportunity for developing innovative materials for bone repair. In this work, a strategy to prepare biomimetic nanofiber-reinforced dually cross-linked (DC) injectable hydrogels with self-healing, osteogenic and angiogenic properties was proposed. The PLGA/MDex/CaP@PBLG nanofiber hydrogels were crosslinked through two reversible dynamic interactions including Schiff base reaction and physical chelation, thereby demonstrating good self-healing property. Meanwhile, the incorporation of CaP@PBLG mineralized nanofibers and alendronate sodium (BP) grafted on PLGA could endow the hydrogels with favorable osteogenic function. Moreover, the introduction of antioxidant ferulic acid (FA) could significantly stimulate angiogenic activity of the hydrogels. The successful regeneration of cranial defects in rats demonstrated a potential application of PLGA/MDex/CaP@PBLG nanofiber hydrogels in the field of bone regeneration.

Multifunctional rare earth oxide/MBG composite microspheres as a carrier for bone tumor treatment

With the development of advanced composites, biomaterials have brought the field of tissue engineering and regeneration into a new era. Among them, composites of inorganic nonmetallic materials and rare earth oxides have unique structures and biochemical properties and have attracted widespread interest. In this work, rare earth oxides (CeO2)/inorganic nonmetallic materials (mesoporous bioactive glass, MBG) composite microspheres (CeO2/MBGs) were synthesized by a sol-gel method, and the in vitro biological effect of CeO2/MBGs was systematically studied. The filling of CeO2/MBGs in irregular bone tumor defects not only promoted osteogenic mineralization in MG63 cells but also had significant antibacterial effects on E. coli and S. aureus. CeO2 enters the MBG network as a network modifier, while doxorubicin (DOX) is adsorbed into the mesoporous structure through electrostatic interactions, which endows CeO2/MBGs with excellent bioactivity and controlled DOX release behavior. Moreover, the results of in vitro experiments showed that the proper addition of rare earth oxides had no toxic effect on normal cells, and the combination of rare earth oxides with antitumor drugs could slow the release of DOX through the use of an intelligent response design system, thus inducing the apoptosis of MG63 cells. This work suggested that combination chemotherapy and the design of a rare earth oxide/MBG composite microspheres may be potential therapeutic approaches for the postoperative repair of bone tumor defects. The construction of this multifunctional rare earth oxide/inorganic biocomposite provides a way to apply the material to bone tissue.

Study on mechanical properties of dual-channel cryogenic 3D printing scaffold for mandibular defect repair.

Mandibular defect repair has always been a clinical challenge, facing technical bottleneck. The new materials directly affect technological breakthroughs in mandibular defect repair field. Our aim is to fabricate a scaffold of advanced biomaterials for repairing of small mandibular defect. Therefore, a novel dual-channel scaffold consisting of silk fibroin/collagen type-I/hydroxyapatite (SCH) and polycaprolactone/hydroxyapatite (PCL/HA) was fabricated by cryogenic 3D printing technology with double nozzles. The mechanical properties and behaviors of the dual-channel scaffold were investigated by performing uniaxial compression, creep, stress relaxation, and ratcheting experiments respectively. The experiments indicated that the dual-channel scaffold was typical non-linear viscoelastic consistent with cancellous tissue; the Young's modulus of this scaffold was 60.1kPa. Finite element analysis (FEA) was employed performing a numerical simulation to evaluate the implantation effect in mandible. The stress distribution of the contact area between scaffold and defect was uniform, the maximum Mises stress of cortical bone and cancellous bone in defect area were 54.520MPa and 3.196MPa, and the maximum displacement of cortical bone and cancellous bone in defect area were 0.1575mm and 0.1555mm respectively, which distributed in the incisor region. The peak maximum Mises stress experienced by the implanted scaffold was 3.128 × 10-3MPa, and the maximum displacement was 6.453 × 10-2mm distributed near incisor area. The displacement distribution of the scaffold was consistent with that of cortical and cancellous bone. The scaffold recovered well when the force applied on it disappeared. Above all, the dual-channel scaffold had excellent bio-mechanical properties in implanting mandible, which provides a new idea for the reconstruction of irregular bone defects in the mandible and has good clinical development prospects.

4D-printed dual-responsive bioscaffolds for treating critical-sized irregular bone defects

Currently, treating irregular bone defects with a critical size is still challenging as material implantation in the complex defects with irregular shapes, effective osteogenesis and sufficient vascularization cannot be easily achieved simultaneously via a simple strategy. Herein, a dual-responsive bone tissue engineering scaffold is developed using a 4D printing strategy by intergrating a single type of multifunctional magnetic nanoparticles, Fe3O4@SiO2, with printing inks made of bioceramics and biopolymers. Minimally invasive implantation, fluent navigation of scaffolds as well as the precise boundary matching between scaffolds and the irregular defects are achieved through near-infrared (NIR) irradiation-based temperature responsive shape recovery and static magnetic field (SMF) stimulation. Moreover, improved bone regeneration in critical-sized bone defects is successfully achieved through the activation of PI3K/AKT pathway which significantly promotes osteogenic differentiation and vascularization. Besides, NIR-based photothermal stimulation upregulates the expression of heat shock protein (HSP90) and further promotes the osteogenesis and vascularization. The in vivo study also confirms that our scaffold can precisely fit the bone defect, and induce satisfactory osteogenesis and angiogenesis. This work provides a facile strategy to simultaneously-realize easy scaffold implantation in irregular bone defects and improves osteogenesis and angiogenesis by integrating a single type of multifunctional nanoparticles with scaffold matrices.

Multi-DORGP for fast uncertainty quantification of multi-scale irregular defects in super large-scale fiber-reinforced composite

The presence of randomly distributed irregular defects in fiber-reinforced composites significantly impacts the structural response, yet traditional machine learning schemes often require an extensive number of samples, resulting in time-consuming processes. Therefore, this paper introduces a novel approach, termed the dual order-reduced Gaussian Process emulators (Multi-DORGP), aimed at efficiently quantifying the uncertainty of multi-scale irregular defects in fiber-reinforced composites. This is achieved by accurately characterizing the multi-scale irregular defects through precise geometric representations, utilizing massive discrete nodes and fine meshes to address the limitations of parameterization methods that may overlook shape and size differences of defects. Moreover, we comprehensively quantify uncertainty across micro, meso, and macro scales, considering spatially randomly distributed locations, sizes, and irregular shapes of defects. Notably, the Multi-DORGP scheme is presented to alleviate the computational burden associated with extremely high-dimensional data (e.g., up to 23.3 million variables). In which, we decouple and build the latent spaces for raw data assisted by principal component analysis, and Gaussian Process regression is built and trained by the coefficients between the latent spaces. Through illustrative examples, including a real-life application involving an airplane wing, we validate the proposed scheme's capability to accurately quantify the uncertainty of multi-scale irregular defects in large-scale fiber-reinforced composites using significantly few samples (e.g., 100).

Injectable microspheres adhering to the cartilage matrix promote rapid reconstruction of partial-thickness cartilage defects

An effective treatment for the irregular partial-thickness cartilage defect in the early stages of osteoarthritis (OA) is lacking. Cartilage tissue engineering is effective for treating full-thickness cartilage defects with limited area. In this study, we designed an injectable multifunctional poly(lactic-co-glycolic acid) (PLGA) microsphere to repair partial-thickness cartilage defects. The microsphere was grafted with an E7 peptide after loading the microsphere with kartogenin (KGN) and modifying the outer layer through dopamine self-polymerization. The microsphere could adhere to the cartilage defect, recruit synovial mesenchymal stem cells (SMSCs) in situ, and stimulate their differentiation into chondrocytes after injection into the articular cavity. Through in vivo and in vitro experiments, we demonstrated the ability of multifunctional microspheres to adhere to cartilage matrix, recruit SMSCs, and promote their differentiation into cartilage. Following treatment, the cartilage surface of the model group with partial-thickness cartilage defect showed smooth recovery, and the glycosaminoglycan content remained normal; the untreated control group showed significant progression of OA. The microsphere, a framework for cartilage tissue engineering, promoted the expression of SMSCs involved in cartilage repair while adapting to cell migration and growth. Thus, for treating partial-thickness cartilage defects in OA, this innovative carrier system based on stem cell therapy can potentially improve therapeutic outcomes. Statement of significanceMesenchymal stem cells (MSCs) therapy is effective in the repair of cartilage injury. However, because of the particularity of partial-thickness cartilage injury, it is difficult to recruit enough seed cells in situ, and there is a lack of suitable scaffolds for cell migration and growth. Here, we developed polydopamine surface-modified PLGA microspheres (PMS) containing KGN and E7 peptides. The adhesion ability of the microspheres is facilitated by the polydopamine layer wrapped in them; thus, the microspheres can adhere to the injured cartilage and recruit MSCs, thereby promoting their differentiation into chondrocytes and accomplishing cartilage repair. The multifunctional microspheres can be used as a safe and potential method to treat partial-thickness cartilage defects in OA.

Endoscopic outcomes using a novel through-the-scope tack and suture system for gastrointestinal defect closure: a systematic review and meta-analysis.

Closure of gastrointestinal defects can reduce postprocedural adverse events. Over-the-scope clips and an over-the-scope suturing system are widely available, yet their use may be limited by defect size, location, operator skill level, and need to reinsert the endoscope with the device attached. The introduction of a through-the-scope helix tack suture system (TTSS) allows for closure of large irregular defects using a gastroscope or colonoscope, without the need for endoscope withdrawal. Since its approval 3 years ago, only a handful of studies have explored outcomes using this novel device. Multiple databases were searched for studies looking at TTSS closure from inception until August 2023. The primary outcomes were the success of TTSS alone and TTSS with clips for complete defect closure. Secondary outcomes included complete closure based on procedure type (endoscopic mucosal resection [EMR], endoscopic submucosal dissection [ESD]) and adverse events. Eight studies met the inclusion criteria (449 patients, mean defect size 34.3 mm). Complete defect closure rates for TTSS alone and TTSS with adjunctive clips were 77.2% (95%CI 66.4-85.3; I2=79%) and 95.2% (95%CI 90.3-97.7; I2=42.5%), respectively. Complete defect closure rates for EMR and ESD were 99.2% (95%CI 94.3-99.9; I2 = 0%) and 92.1% (95%CI 85-96; I2=0%), respectively. The adverse event rate was 5.4% (95%CI 2.7-10.3; I2=55%). TTSS is a novel device for closure of postprocedural defects, with relatively high technical and clinical success rates. Comparative studies of closure devices are needed.

Dynamic Proteinaceous Hydrogel Enables In‐Situ Recruitment of Endogenous TGF‐β1 and Stem Cells for Cartilage Regeneration

AbstractArticular cartilage is a tissue with relatively poor self‐regeneration capacity due to insufficient blood vessels and chondrocytes in the region. Biomaterial‐assisted tissue engineering has shown great potential in cartilage regeneration. However, there are still many worries over the uses of exogenous growth factors, stem cells and scaffolds. To address these concerns, here a dynamic proteinaceous hydrogel with a self‐recruiting ability of cartilage‐inducing factor for in situ cartilage regeneration is reported. The dynamic hydrogel (Pep‐GelSH) is prepared by using thiol‐modified gelatin and thiol‐capped TGF‐β1‐affinity peptide through the Au‐S coordination. The injectability and self‐recovery of Pep‐GelSH hydrogel enabled not only minimally invasive implantation but also the adaptability of the scaffold to irregular defect shapes. Meanwhile, the dynamic hydrogel showed improved adherence to the host tissue and allowed quick infiltration of host cells. More importantly, the hydrogel significantly enhanced local enrichment of endogenous TGF‐β1 and led to the recruitment of stem cells in vivo. After implantation, the hydrogel scaffold triggered the innate repair capacity of cartilage defects by successively promoting stem cells recruitment, infiltration and differentiation, resulting in significantly enhanced chondrogenesis and improved cartilage repair. Therefore, the study in this work may provide a feasible and promising approach for in situ cartilage regeneration.

Cryogel wound dressings based on natural polysaccharides perfectly adhere to irregular wounds for rapid haemostasis and easy disassembly.

Skin injuries can have unexpected surfaces, leading to uneven wound surfaces and inadequate dressing contact with these irregular surfaces. This can decrease the dressing's haemostatic action and increase the healing period. This study recommends the use of sticky and flexible cryogel coverings to promote faster haemostasis and efficiently handle uneven skin wounds. Alginate cryogels have a fast haemostatic effect and shape flexibility due to their macroporous structure. The material demonstrates potent antibacterial characteristics and enhances skin adherence by adding grafted chitosan with gallic acid. In irregular defect wound models, cryogels can cling closely to uneven damage surfaces due to their amorphous nature. Furthermore, their macroporous structure allows for quick haemostasis by quickly absorbing blood and wound exudate. After giving the dressing a thorough rinse, its adhesive strength reduces and it is simple to remove without causing any damage to the wound. Cryogel demonstrated faster haemostasis than gauze in a wound model on a rat tail, indicating that it has considerable potential for use as a wound dressing in the biomedical area.

Electron-translucency and partial defects of synaptic basal lamina in the electrocyte synapse of an electric ray (Narke japonica) in 3D embedment-free section electron microscopy.

The synaptic basal lamina of the electrocytes was disclosed to be electron-translucent to some extent when viewed in an en-face direction in embedment-free section transmission electron microscopy (EFS-TEM), and synaptic vesicles located close to the presynaptic membrane were seen through the synaptic basal lamina together with the presynaptic and postsynaptic membranes. This feature of translucency has the potential to analyze possible spatial interrelations in situ between bioactive molecules in the synaptic basal lamina and the synaptic vesicles in further studies. The synaptic basal lamina, appearing as an electron-dense line sandwiched by two parallel lines representing the presynaptic and postsynaptic membranes in ultrathin sections cut right to the synaptic junctional plane in conventional TEM, was not fully continuous but randomly intermittent along its trajectory. Compatible with the intermittent line appearance, the en-face 3D view in embedment-free section TEM revealed for the first time partial irregular defects of the synaptic basal lamina. Considering the known functional significance of several molecules contained in the synaptic basal lamina in the maintenance and exertion of the synapse, its partial defects may not represent its rigid structural features, but its immature structure under remodeling or its dynamic changes in consistency such as the sol/gel transition, whose validity needs further examination. RESEARCH HIGHLIGHTS: In embedment-free section TEM, a 3D en-face view of synaptic basal lamina in situ is reliably possible. The basal lamina en-face is electron-translucent, which makes it possible to analyze spatial interrelation between pre- and post-synaptic components. Partial irregular defects in the basal lamina are revealed in Torpedo electrocytes, suggesting its remodeling or dynamic changes in consistency.

Injectable and In Situ Formed Dual-Network Hydrogel Reinforced by Mesoporous Silica Nanoparticles and Loaded with BMP-4 for the Closure and Repair of Skull Defects.

Bone defects are a common and challenging orthopedic problem with poor self-healing ability and long treatment cycles. The difficult-to-heal bone defects cause a significant burden of medical expenses on patients. Currently, biomaterials with mechanical stability, long-lasting action, and osteogenic activity are considered as a suitable way to effectively heal bone defects. Here, an injectable double network (DN) hydrogel prepared using physical and chemical cross-linking methods is designed. The first rigid network is constructed using methylpropenylated hyaluronic acid (HAMA), while the addition of chitosan oligosaccharide (COS) forms a second flexible network by physical cross-linking. The mesoporous silica nanoparticles (MSN) loaded with bone morphogenetic protein-4 (BMP-4) were embedded into DN hydrogel, which not only enhanced the mechanical stability of the hydrogel, but also slowly released BMP-4 to achieve long-term skull repair. The designed composite hydrogel showed an excellent compression property and deformation resistance. In vitro studies confirmed that the HAMA/COS/MSN@BMP-4 hydrogel had good biocompatibility and showed great potential in supporting proliferation and osteogenic differentiation of mouse embryo osteoblast precursor (MC3T3-E1) cells. Furthermore, in vivo studies confirmed that the DN hydrogel successfully filled and closed irregular skull defect wounds, effectively promoted bone regeneration, and significantly promoted bone repair compared with the control group. In addition, HAMA/COS/MSN@BMP-4 hydrogel precursor solution can quickly form hydrogel in situ at the wound by ultraviolet light, which can be applied to the closure and repair of wounds of different shapes, which provides the new way for the treatment of bone defects.

Clay Sculpture-Inspired 3D Printed Microcage Module Using Bioadhesion Assembly for Specific-Shaped Tissue Vascularization and Regeneration.

3D bioprinting techniques have enabled the fabrication of irregular large-sized tissue engineering scaffolds. However, complicated customized designs increase the medical burden. Meanwhile, the integrated printing process hinders the cellular uniform distribution and local angiogenesis. A novel approach is introduced to the construction of sizable tissue engineering grafts by employing hydrogel 3D printing for modular bioadhesion assembly, and a poly (ethylene glycol) diacrylate (PEGDA)-gelatin-dopamine (PGD) hydrogel, photosensitive and adhesive, enabling fine microcage module fabrication via DLP 3D printing is developed. The PGD hydrogel printed micocages are flexible, allowing various shapes and cell/tissue fillings for repairing diverse irregular tissue defects. In vivo experiments demonstrate robust vascularization and superior graft survival in nude mice. This assembly strategy based on scalable 3D printed hydrogel microcage module could simplify the construction of tissue with large volume and complex components, offering promise for diverse large tissue defect repairs.