Defect Model Research Articles

A Frugal Approach Toward Modeling of Defects in Metal 3D Printing Through Statistical Methods in Finite Element Analysis

Metal additive manufacturing has emerged as a revolutionary technology for the fabrication of high-complexity components. However, this technique presents unique challenges related to the structural integrity and final strength of the parts produced due to inherent defects, such as porosity, cracks, and geometric deviations. These defects significantly impact the fatigue life of the material by acting as stress concentrators that accelerate failure under cyclic loading. On the one hand, this type of model is very complicated in its approach, since, even with encouraging results, the complexity of the calculation with these variables makes it difficult to obtain a simple result that allows for a generalized interpretation. On the other hand, using more familiar methods, it is possible to qualitatively guess the behavior that helps obtain results with better applicability, even at limited levels of precision. This paper presents a simplified finite element method combined with a statistical approach to model the presence of porosity in metal components produced by additive manufacturing. The proposed model considers a two-dimensional square plate subjected to tensile stress, with randomly introduced defects characterized by size, shape, and orientation. The percentage of porosity that affects each aspect determines the adjustment of the mechanical properties of finite elements. A series of simulations were performed to generate multiple models with random defect distributions to estimate maximum stress values. This approach demonstrates that complex models are not always necessary for a preliminary practical estimate of the effects of new manufacturing techniques. Furthermore, it demonstrates the potential for the extension of frugal computational techniques, which aim to minimize computational and experimental costs in the engineering field. The article discusses future research directions, particularly those related to potential business applications, including commercial uses. This follows a discussion of the existing limitations of this study.

An automatic defect detection and localization method using imaging geometric features for sewer pipes

Accurate longitudinal localization of defects in sewer pipes is crucial for efficient maintenance and renewal. However, traditional closed-circuit television (CCTV)-based localization methods have been inefficient and imprecise, impeding real-time inspection performance. In this paper, we firstly point out that the inaccuracy of CCTV-based localization methods stems from the oversight of monocular imaging geometry, which leads to a deviation in sewer defect localization. Then, we propose an automated framework for sewer defect detection and longitudinal localization based on a deep-learning algorithm and monocular imaging geometry. Specifically, structural defects are qualitatively analyzed to explore their intrinsic correlation with the pipe wall. Then, the imaging geometry is leveraged to establish the projection relationship between the defects and the pipe joints. The longitudinal localization correction model for structural defects is then developed using the pipe diameter as the actual size. Our experiments show that this framework enhances the mean average precision (mAP) for multi-defects by 7.2 % and achieves a theoretical mean absolute error of 0.2 m and a practical mean absolute error of 0.28 m for defect localization, surpassing current research. Finally, with the generated detection results and localization records, the proposed framework can promote the efficiency of the sewer investigation and accelerate the development of intelligent sewer systems.

Catechol-grafted chitosan-based antioxidant hydrogel with rapid self-healing property for wound healing.

Chronic wounds, particularly those with non-healing ulcers, show high levels of oxidant stress, such as excessive reactive oxygen species (ROS), which delays the healing process. Bacterial infections in wounds increase the need for antibiotics, which brings up serious concerns regarding antibiotic resistance. The innovative antibiotic-free strategies to endow the hydrogels with antibacterial and antioxidant features including the grafting of ROS-scavenging moieties onto the hydrogel structure are in high demand for wound management. Herein, an antibacterial and antioxidant hydrogel with rapid self-healing performance was fabricated via the dynamic borate ester cross-linkages between catechol-grafted chitosan (CS-CA) and polyvinyl alcohol in the presence of borax with the incorporation of ellagic acid (EA). Benefiting from the catechol groups from EA and CS-CA, the resulting hydrogel exhibited desirable adhesive property, excellent antioxidant and intensified antibacterial dual functions. Furthermore, the hydrogel demonstrated remarkable biocompatibility and pH-responsive behavior for the controlled release of EA, attributed to the reversible characteristics of borate ester linkages. Notably, these multifunctional hydrogels exhibited substantial regenerative capabilities in wound healing, as evidenced by in vivo assessments conducted on a full-thickness skin defect model, highlighting their considerable potential as wound dressings for effective wound management.

Peptide platform for 3D-printed Ti implants with synergistic antibacterial and osteogenic functions to enhance osseointegration.

Bone defects caused by trauma, infection, or tumors present a major clinical challenge. Titanium (Ti) implants are widely used due to their excellent mechanical properties and biocompatibility; however, their high elastic modulus, low surface bioactivity, and susceptibility to infection hinder osseointegration and increase failure rates. There is an increasing demand for implants that can resist bacterial infection while promoting osseointegration. In this study, we developed a peptide platform to engineer a multifunctional 3D-printed Ti implant (3DTi) modified with a fusion peptide composed of minTBP-1 (targeting peptide), KR-12 (antibacterial peptide), and GFOGER (adhesion peptide), termed 3DTi-NFP. This design enables specific targeting, localized delivery, prevention of peptide release into circulation, and functional integrity through linker retention. In both in vitro and in vivo infected bone defect models, 3DTi-NFP implants demonstrated excellent biocompatibility and achieved over 90% bactericidal efficiency against S. aureus and E. coli. The implants reduced bacterial colonization while enhancing adhesion, proliferation, and differentiation of bone marrow mesenchymal stem cells (BMSCs), significantly upregulating osteogenic genes and protein expression. Transcriptome sequencing further explored the molecular mechanisms underlying the synergistic effects of 3DTi-NFP, revealing activation of the focal adhesion and PI3K-Akt signaling pathways-key contributors to cell adhesion, matrix formation, and new bone formation. Overall, this study provides a promising strategy to improve the long-term success of Ti-based implants, with significant potential for tissue regeneration and clinical applications.

Incorporating Bone-Derived ECM into Macroporous Microribbon Scaffolds Accelerates Bone Regeneration.

Tissue-derived extracellular matrix (tdECM) hydrogels serve as effective scaffolds for tissue regeneration by promoting a regenerative immune response. While most tdECM hydrogels are nanoporous and tailored for soft tissue, macroporosity is crucial for bone regeneration. Yet, there's a shortage of macroporous ECM-based hydrogels for this purpose. The study aims to address this gap by developing a co-spinning technique to integrate bone-derived ECM (bECM) into gelatin-based, macroporous microribbon (µRB) scaffolds. The effect of varying doses of bECM on scaffold properties was characterized. In vitro studies revealed 15% bECM as optimal for promoting MSC osteogenesis and macrophage (Mφ) polarization. When implanted in a mouse critical-sized cranial bone defect model, 15% bECM with tricalcium phosphate (TCP) microparticles significantly accelerated bone regeneration and vascularization, filling over 55% of the void by week 2. Increasing bECM to 25% enhanced mesenchymal stem cell (MSC) recruitment and decreased M1 Mφ polarization but reduced overall bone formation and vascularization. The findings demonstrate co-spun gelatin/bECM hydrogels as promising macroporous scaffolds for robust endogenous bone regeneration, without the need for exogenous cells or growth factors. While this study focused on bone regeneration, this platform holds the potential for incorporating various tdECM into macroporous scaffolds for diverse tissue regeneration applications.

Exploring the therapeutic potential of small extracellular vesicles derived from induced pluripotent stem cell in periodontal regeneration.

To investigate the role of small extracellular vesicles derived from induced pluripotent stem cells (iPSC-sEVs) in periodontal tissue regeneration, elucidate their potential molecular mechanisms, and provide theoretical guidance for the clinical application of iPSC-sEVs as a cell-free therapeutic strategy for periodontal tissue regeneration. We investigated the effects of iPSC-sEVs on the proliferation, migration, and osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in vitro. The regenerative potential of iPSC-sEVs was evaluated in vivo, using a periodontal defect model. Bulk RNA sequencing was performed to elucidate the underlying molecular mechanisms. iPSC-sEVs were isolated, characterized, and systemically evaluated for regenerative potential. The results revealed that treatment with iPSC-sEVs significantly enhanced the proliferation, migration, and osteogenic differentiation of PDLSCs. In situ treatment with iPSC-sEVs loaded onto collagen sponges was performed in a rat model of periodontal defects. Micro-CT and histological analyses indicated that iPSC-sEV treatment markedly promoted alveolar bone repair and periodontal ligament regeneration. Mechanistically, the analysis of bulk RNA sequencing data coupled with experimental validation revealed that iPSC-sEV treatment significantly activated the mitogen-activated protein kinase (MAPK) signaling pathway in PDLSCs. Further investigation showed that the inhibition of this pathway completely abolished the proliferative effects of iPSC-sEVs on PDLSCs. iPSC-sEVs promote PDLSC proliferation through MAPK signaling pathway activation, while also enhancing PDLSC migratory and osteogenic differentiation capacities, facilitates the repair and regeneration of damaged periodontal tissue and presents a potential novel therapeutic strategy for clinical periodontal tissue regeneration.

Enhanced bone regeneration using mesenchymal stem cell-loaded 3D-printed alginate-calcium Titanate scaffolds: A Calvarial defect model study.

This study investigates the efficacy of a 3D-printed alginate composite scaffold enriched with calcium titanate nano powders and loaded with mesenchymal stem cells (MSCs) for bone regeneration in a calvarial defect model. Scaffolds (20 mm × 20 mm × 4.48 mm) with a slightly rough surface texture were fabricated using a bioprinter. A calvarial defect was created in the skulls of forty male Wistar rats, then divided into four treatment groups: empty defect, scaffold only, MSCs only, and MSC-seeded scaffold. After eight weeks, new bone formation was evaluated. The MSC-seeded scaffold group showed superior outcomes, including significantly higher bone mineral density (BMD), nearly complete defect closure in CT imaging, and enhanced histological results with newly formed bone and marrow cavities. Osteogenic gene markers (RunX2, OSX, COL1, BMP2, and OCN) and the angiogenic marker VEGF were notably upregulated, while the osteoclast-related gene RANKL was downregulated. These findings highlight the synergistic effect of the scaffold's osteoconductive properties and MSCs' regenerative potential. MSC-seeded alginate‑calcium titanate scaffold demonstrates promising results for critical-sized defect repair and may serve as a viable strategy for clinical bone tissue engineering applications.

The Effect of Cryopreservation on the Bone Healing Capacity of Endothelial Progenitor Cells in a Bone Defect Model.

Endothelial progenitor cells (EPCs) have proven to be a highly effective cell therapy for critical-sized bone defects. Cryopreservation can enable long-term storage of EPCs, allowing their immediate availability on demand. This study compares the therapeutic potential of EPCs before and after cryopreservation in a small animal critical-sized bone defect model. Five-millimeter segmental defects were created in the right femora of Fischer 344 rats, followed by stabilization with a miniplate and screws. The animals received 2 × 106 fresh EPCs (n = 7) or 2 × 106 cryopreserved EPCs (n = 9) delivered on a gelatin scaffold. Cryopreserved EPCs were stored for 7 days at -80°C prior to thawing and loading onto the gelatin scaffold. Biweekly radiographs were taken until the animals were euthanized 10 weeks after surgery. The operated femora were then evaluated using microscopic-computed tomography (micro-CT) and biomechanical testing. All animals treated with fresh (n = 7/7) or cryopreserved (n = 9/9) EPCs achieved radiographic union at 10 weeks. Animals treated with fresh EPCs had statistically significant higher radiographic scores at 2 weeks (p < 0.05) but showed no statistically significant differences thereafter (p > 0.05). Micro-CT analysis showed no statistically significant differences between the groups in bone volume (BV) or BV normalized to total volume (p > 0.05), with excellent bone formation in both groups. Finally, there were no differences in biomechanical outcomes between the groups (p > 0.05). These results demonstrate that cryopreserved EPCs are highly effective and equivalent to fresh EPCs for healing critical-sized bone defects in a rat model of nonunion.

In situ osteogenic activation of mesenchymal stem cells by the blood clot biomimetic mechanical microenvironment

Blood clots (BCs) play a crucial biomechanical role in promoting osteogenesis and regulating mesenchymal stem cell (MSC) function and fate. This study shows that BC formation enhances MSC osteogenesis by activating Itgb1/Fak-mediated focal adhesion and subsequent Runx2-mediated bone regeneration. Notably, BC viscoelasticity regulates this effect by modulating Runx2 nuclear translocation. To mimic this property, a viscoelastic peptide bionic hydrogel named BCgel was developed, featuring a nanofiber network, Itgb1 binding affinity, BC-like viscoelasticity, and biosafety. The anticipated efficacy of BCgel is demonstrated by its ability to induce nuclear translocation of Runx2 and promote bone regeneration in both in vitro experiments and in vivo bone defect models with blood clot defect, conducted on rats as well as beagles. This study offers insights into the mechano-transduction mechanisms of MSCs during osteogenesis and presents potential guidelines for the design of viscoelastic hydrogels in bone regenerative medicine.

An antibacterial, antioxidant and hemostatic hydrogel accelerates infectious wound healing

Hydrogel drug-delivery system that can effectively load antibacterial drugs, realize the in-situ drug release in the microenvironment of wound infection to promote wound healing. In this study, a multifunctional hydrogel drug delivery system (HA@TA-Okra) was constructed through the integration of hyaluronic acid methacrylate (HAMA) matrix with tannic acid (TA) and okra extract. The composition and structural characteristics of HA@TA-Okra system and its unique advantages in the treatment of diverse wounds were systematically evaluated. TA, due to its unique chemical structure, is able to anchor within the HAMA network through interactions and cross-linking, conferring exceptional mechanical strength and stability to the hydrogel. Both TA and okra extract possess antioxidant and antibacterial properties, and when they two acts synergistically they can effectively scavenge free radicals, enhance antibacterial action, diminishing the risk of wound infection. In vitro experiments revealed that HA@TA-Okra system has superior properties, such as rapid gel response, remarkable swelling regulation, and potent antioxidant ability. Furthermore, the HA@TA-Okra system significantly outperformed conventional dressings in terms of hemostatic performance in a rat hemorrhage model. We further evaluated the repair role of HA@TA-Okra system in vivo by establishing an animal model of full-thickness skin defects and a model of infected total skin defects. The results confirmed its positive effects in fighting bacterial infection, reducing inflammation and promoting wound healing. In summary, the HA@TA-Okra system exhibits comprehensive properties such as antibacterial, antioxidant and hemostatic properties, which has a potential application in the field of tissue repair medicine.Graphical

Trap density estimation for TDDB testing in SiC power MOSFETs

Abstract The trap density estimation of SiC power MOSFET in time-dependent dielectric breakdown (TDDB) was investigated by using experiment and TCAD simulation. The gate leakage current (IGSS) under negative voltage was measured and a current spike was found which was linearly shifted with TDDB stress. Based on four-state nonradiative multi phonon (NMP) defect capture model, the mechanism and modeling of IGSS current spike was studied. Based on TCAD simulation, the characteristics of gate oxygen donor traps including trap energy level, trap density, and position distribution were estimated, and the trap density model in TDDB experiment was proposed and verified. This study may contribute to the estimation of trap density in SiC MOSFET.&amp;#xD;

Comparison of two plates and screw osteosynthesis configurations in a rat model of critical sized femoral defects to reduce implant related failures

This study aimed to compare the failure rates of two different sizes of plates and screws to stabilize critical-sized (7 mm) femoral defects in male Sprague‒Dawley rats (aged 10 weeks). Femoral defects were stabilized with either a 4-hole plate (length 29 mm, thickness 1 mm, 10 rats, Group 1) and 4 cortical screws (diameter 2 mm) or with a 6-hole plate (length 30 mm, thickness 0.6 mm, 9 rats, Group 2) and 4 cortical screws (diameter 1.5 mm). A polymethylmethacrylate spacer was inserted into the defects to reproduce the first stage of the induced membrane technique. Radiographic evaluations, macroscopic and histologic assessments of the induced membranes were conducted at 1 week and 4 weeks. No implant failure occurred in Group 1 whereas in Group 2, 4/9 (44.4%) implant failures occurred during the follow-up (p = 0.03). On histomorphometry, cell density was higher in Group 1 (4996 ± 716 cells / mm²) than in Group 2 (3500 ± 728 cells/mm²) (p = 0.0195) but the membrane thickness in Group 1 (735 ± 44 μm) was non-significantly lower than in Group 2 (979 ± 165 μm) (p = 0.4). This study suggests that, in rat models of critical-sized femoral defects (7 mm) to study the induced membrane technique, fixation plates with a thickness of 1 mm and four screws (2 mm in diameter) provide stable fixation without implant failure. In contrast, thinner plates (< 1 mm) combined with screws of smaller diameter (1.5 mm) result in a high rate of implant failure.

Rat model of nerve regeneration

Abstract Introduction Peripheral nerve injuries affect numerous patients annually, with outcomes influenced by factors such as the nerve’s regenerative capacity, injury severity, and the surgeon’s technical skill. Animal models are essential for refining surgical techniques and exploring new therapies to improve nerve regeneration. The choice of animal model depends on the target nerve. This study describes a standardized rat sciatic nerve defect model. Methods The sciatic nerve defect model involves the rat under deep anesthesia. The lateral thigh area is shaved and disinfected with chlorhexidine. A 3 cm incision is made below the femur, followed by the identification of the superficial gluteal and biceps femoris muscles using scissors and forceps. The sciatic nerve, located between the two muscle heads, is isolated by cutting the fascia and dissecting the muscle heads. A background band is placed to isolate the nerve from surrounding structures. After implementing the selected technique and treatment, the incision is closed in layers. For skin closure, intradermal sutures are used to prevent the rats from biting protruding threads. Results This rat sciatic nerve defect model supports various follow-up evaluations, including the sciatic functional index, ultrasonography, electromyography, MRI, genetic studies, histopathology, immunohistochemistry, and transmission electron microscopy. Conclusion This rat sciatic nerve model is easy to replicate and provides a robust platform for studying nerve regeneration.

Universal Hydrogel Carrier Enhances Bone Graft Success: Preclinical and Clinical Evaluation.

Orthopedic, maxillofacial, and complex dentoalveolar bone grafting procedures that require donor-site bone harvesting can be associated with post-surgical complications. There has been widespread adoption of exogenously sourced particulate bone graft materials (BGM) for bone regenerative procedures; however, the particulate nature of these materials may lead to compromised healing outcomes, mainly attributed to structural collapse of the BGM, prolonged tissue healing. In this study, a fully synthetic thermoresponsivehydrogel-based universal carrier matrix (TX) that forms flowable and shapable putties with different BGMs while spatially preserving the particles in a 3D scaffold at the implantation site is introduced. The potential synergistic effect of the carrier is investigated in combination with particulate demineralized bone matrix (DBM) in a standard muscle pouch nude mice model (n = 24) as well as in a rabbit femoral critical-sized cortico-cancellous bone defect model (n = 9). Finally, the clinical usability, safety, and efficacy of the carrier for the delivery of deproteinized bovine bone mineral (DBBM) are evaluated in a controlled clinical trial for extraction socket alveolar ridge preservation (ARP) (n = 11 participants). Overall, theTX carrier improved the delivery of different types of BGMs, maintaining these spatially at the implantation site with minimal inflammatory responses, resulting in favorable bone regenerative outcomes.

Polypropylene Mesh Coated with Dual Cross‐Linked Hyaluronic Acid/Polyvinyl Alcohol Composite Hydrogel with Antiadhesion and Angiogenesis Properties for Abdominal Wall Repair

AbstractDevelopment of an antiadhesion polypropylene (PP) mesh in hernia repair is a recognized need because its efficacy is limited by severe abdominal adhesions. The porous structure of PP mesh can facilitate the integration between prosthetic material and abdominal tissue and promote the repair of abdominal wall defect. Herein, an antiadhesion composite hydrogel coating composed of polyvinyl alcohol (PVA) and hyaluronic acid methacrylate (HAMA) is fabricated on the surface of PP mesh through ultraviolet photopolymerization combined with freezing–thawing method. The resulted composite hydrogel coated PP mesh retain 43.33% of the pore structure by this way. In vitro tests proved the as‐prepared PP mesh exhibit excellent hydrophilicity and biocompatibility. Meanwhile, the hydrogel coating shows good stability on the surface of PP mesh in phosphate buffered saline medium. After implantation in a rat abdominal wall defect model, the modified PP mesh effectively prevents the formation of adhesion by reducing inflammatory response and suppressing excessive deposition of collagen fiber. Immunohistochemical staining results demonstrate that the modified PP mesh can not only decrease the expression of IL‐6, TNF‐α, and CD68 but also promote the expression of CD31. Thus, this type of PP mesh with preventing postoperative adhesions and improving angiogenesis may be a promising clinical prosthetic material.

Masquelet Inspired in Vivo Engineered Extracellular Matrix as Functional Periosteum for Bone Defect Repair and Reconstruction.

The Masquelet technique that combines a foreign body reaction (FBR)-induced vascularized tissue membrane with staged bone grafting for reconstruction of segmental bone defect has gained wide attention in Orthopedic surgery. The success of Masquelet hinges on its ability to promote formation of a "periosteum-like" FBR-induced membrane at the bone defect site. Inspired by Masquelet's technique, here a novel approach is devised to create periosteum mimetics from decellularized extracellular matrix (dECM), engineered in vivo through FBR, for reconstruction of segmental bone defects. The approach involved 3D printing of polylactic acid (PLA) template with desired pattern/architecture, followed by subcutaneous implantation of the template to form tissue, and depolymerization and decellularization to generate dECM with interconnected channels. The dECM matrices produces from the same mice (autologous) or from different mice (allogenic) are used as a functional periosteum for repair of structural bone allograft in a murine segmental bone defect model. This study shows that autologous dECM performed better than allogenic dECM, further permitting local delivery of low dose BMP-2 to enhance allograft incorporation. The success of this current approach can establish a new line of versatile, patient-specific, and periosteum-like autologous dECM for bone regeneration, offering personalized therapeutics to patients with impaired healing.

Low-Intensity Pulsed Ultrasound Responsive Scaffold Promotes Intramembranous and Endochondral Ossification via Ultrasonic, Thermal, and Electrical Stimulation.

Multiple physical stimuli are expected to produce a synergistic effect to promote bone tissue regeneration. Low-intensity pulsed ultrasound (LIPUS) has been clinically used in bone repair for the mechanical stimulation that it provides. In addition, LIPUS can also excite the biomaterials to generate other physical stimuli such as thermal or electrical stimuli. In this study, a scaffold based on decellularized adipose tissue (DAT) is established by incorporating polydopamine-modified multilayer black phosphorus nanosheets (pDA-mBP@DAT). Their effect on bone repair under LIPUS stimulation and the potential mechanisms are further investigated. This scaffold possesses piezoelectric properties and generates a mild thermogenic stimulus when stimulated by LIPUS. With superior properties, this scaffold is demonstrated to have good cytocompatibility in vitro and in vivo. Simultaneously, LIPUS promotes cell attachment, migration, and osteogenic differentiation in the pDA-mBP@DAT scaffold. Furthermore, the combined use of pDA-mBP@DAT and LIPUS significantly affects the regenerative effect in rat models of critical-sized calvarial defects. The possible mechanisms include promoting osteogenesis and neovascularization and activating the Piezo1. This study presents insight into speeding up bone regeneration by the synergistic combination of LIPUS and pDA-mBP@DAT scaffolds.

Prediction Model for Flake Line Defects in Metallic Injection Molding: Considering Skin-Core Velocity and Alignment.

Metallic injection molding combines aluminum flake metallic pigments with polymers to directly produce components with metallic luster, improving production efficiency and reducing environmental impact. However, flake line defects that occur in regions where ribs or flow paths intersect remain a significant challenge. This study proposes a velocity model that considers the flow characteristics between the surface and core layers and an alignment model that incorporates the orientation of aluminum flakes to predict appearance defects. Through this approach, the mechanisms of appearance defect formation were systematized, and the appearance defects caused by flow velocity differences between the surface and core layers, flake alignment uniformity, and reflection angles were visualized. Both prediction models demonstrated a 50% prediction accuracy, successfully identifying two out of four observed defects. This research addresses the limitations of previous prediction methods, which only considered the surface layer, by introducing a novel approach that accounts for the core layer. It is expected to contribute to reducing defects and improving quality in industries requiring high-quality metallic appearances.

An injectable multi-functional composite bioactive hydrogel for bone regeneration via immunoregulatory and osteogenesis effects

Bone defects represent a prevalent and significant challenge in clinical practice. Given the inflammatory microenvironment at injury sites and the requirement for endogenous cell and tissue infiltration, there is an urgent need for an ideal biomaterial that can modulate inflammation and promote bone regeneration. We developed an innovative injectable hydrogel (CH@PUE&MSN) designed for immunomodulation and bone regeneration through in situ self-assembly, incorporating puerarin and chitosan with mesoporous silica nanoparticles. In vitro experiments demonstrated that this multifunctional injectable hydrogel promotes tissue cell regeneration, reduces inflammation, inhibits osteoclast formation, induces the migration and differentiation of bone marrow mesenchymal stem cells, and facilitates bone regeneration. Furthermore, we conducted an extensive in vivo evaluation using a bone defect model, employing advanced imaging and histological analyses. Our findings indicate that this multifunctional injectable hydrogel is a promising bioactive material for bone regeneration and presents a novel strategy for the clinical management of bone defects.

Isogenic Transplantation of Hybrid Artificial Pleural Tissue Consisting of Rat Cells and Polyglycolic Acid Nanofiber Sheet Induces Restoration of Mesothelial Defects in Rat Model.

Impairment of the visceral pleura following thoracic surgery often leads to air leaks and intrathoracic adhesions. For preventing such complications, mesothelial cell proliferation at the pleural defects can be effective. To develop new materials for pleural defects restoration, we constructed a hybrid artificial pleural tissue (H-APLT) combining polyglycolic acid (PGA) nanofiber sheets with a three-dimensional culture of mesothelial cells and fibroblasts and evaluated its therapeutic efficacy in a rat pleural defect model. After rat lungs were harvested, pleural mesothelial cells and lung fibroblasts were cultured separately. To construct H-APLT, the cells were then coated with multiple layers of fibronectin and gelatin, followed by a single layer of mesothelial cells on top of multiple layers of fibroblasts accumulated onto a collagen-coated PGA nanofiber sheet. Left lateral thoracotomy was performed, and H-APLTs were transplanted into a rat model with pleural defects (N = 8). After 2-12 weeks of transplantation, lung resection and histological analyses were performed. H-APLTs exhibited a pleural structure with a highly integrated mesothelial layer invitro. After transplantation, all eight rats survived until sacrifice. At 12 weeks post-transplantation, the mesothelial layer on the lung surface was observed to be without defects with no intrathoracic adhesions detected. Successful isogenic engraftment of H-APLTs was achieved in a rat model of pleural defects. The combination of accumulated fibroblasts and collagen-coated PGA nanofiber sheets contributed to the maintenance of the mesothelial layer's structure and function, potentially preventing air leaks and intrathoracic adhesions.