Tissue Growth Research Articles

Clinical comprehensive treatment protocol for managing diabetic foot ulcers: A retrospective cohort study.

Diabetic foot ulcers (DFUs) are a common complication of diabetes, often leading to severe infections, amputations, and reduced quality of life. The current standard treatment protocols for DFUs have limitations in promoting efficient wound healing and preventing complications. A comprehensive treatment approach targeting multiple aspects of wound care may offer improved outcomes for patients with DFUs. The hypothesis of this study is that a comprehensive treatment protocol for DFUs will result in faster wound healing, reduced amputation rates, and improved overall patient outcomes compared to standard treatment protocols. To compare the efficacy and safety of a comprehensive treatment protocol for DFUs with those of the standard treatment protocol. This retrospective study included 62 patients with DFUs, enrolled between January 2022 and January 2024, randomly assigned to the experimental (n = 32) or control (n = 30) group. The experimental group received a comprehensive treatment comprising blood circulation improvement, debridement, vacuum sealing drainage, recombinant human epidermal growth factor and anti-inflammatory dressing, and skin grafting. The control group received standard treatment, which included wound cleaning and dressing, antibiotics administration, and surgical debridement or amputation, if necessary. Time taken to reduce the white blood cell count, number of dressing changes, wound healing rate and time, and amputation rate were assessed. The experimental group exhibited significantly better outcomes than those of the control group in terms of the wound healing rate, wound healing time, and amputation rate. Additionally, the comprehensive treatment protocol was safe and well tolerated by the patients. Comprehensive treatment for DFUs is more effective than standard treatment, promoting granulation tissue growth, shortening hospitalization time, reducing pain and amputation rate, improving wound healing, and enhancing quality of life.

Biodegradable quaternized silk fibroin sponge with highly uniform pore structure for traumatic hemostasis and anti-infection

Developing a biodegradable sponge with rapid shape recovery and potent antibacterial and coagulation properties for traumatic hemostasis and anti-infection remains challenging. Herein, we fabricated quaternized silk fibroin (SF) sponges by freeze-drying under a constant cooling rate and modification with quaternary ammonium groups. We found the constant cooling rate enabled the sponges with a highly uniform pore structure, which provided excellent self-elasticity and shape recovery. Decoration with quaternary ammonium groups enhanced blood cells adhesion, aggregation, and activation, as well as resistance to infections from Staphylococcus aureus and Escherichia coli. The SF sponge had superior hemostatic capacity to gauze and commercial gelatin sponge in different hemorrhage models. The SF sponge exhibited favorable biodegradability and biocompatibility. Moreover, The SF sponge also promoted host cell infiltration, capillary formation, and tissue ingrowth, suggesting its potential for guiding tissue regeneration. The developed SF sponge holds great application prospects for traumatic hemostasis, anti-infection, and guiding tissue regeneration.

Biomechanical and Histological Study of Retrieved LARS Synthetic Ligaments.

Synthetic grafts have been used for a number of years in anterior cruciate ligament (ACL) reconstruction surgery. One of the more recent additions to the stable of synthetic ligaments is the Ligament Augmentation and Reconstruction System (LARS) ligament. To analyze the biomechanics and histology of LARS grafts retrieved due to failure of the device. Descriptive laboratory study. A total of 22 LARS ligament grafts that were explanted from patients were sent for analysis. Five new, unused samples of the standard LARS ACL graft were also analyzed. Biomechanical testing was performed: ultimate tensile force, force versus displacement, and stress versus strain were recorded. Histopathological examination was performed looking for degree of fibrous tissue ingrowth as well as the presence of a foreign body reaction. Of the 22 grafts retrieved, 14 were used for ACL grafts, 1 for a lateral collateral ligament graft, 2 for medial collateral ligament grafts, 4 for gluteal tendon augmentation, and 1 for a supraspinatus augmentation. A severe foreign body reaction was found in 86% of the grafts (18/22) and a mild foreign body reaction in the remaining 14% (4/22). Tissue ingrowth was minimal in the majority of ACL grafts; the other grafts showed moderate tissue ingrowth. Maximal tensile force was significantly higher for the new ACL grafts (mean ± SD, 1667 ± 845 N) compared with the retrieved grafts (897 ± 395 N; P < .05). This study demonstrated that the vast majority of retrieved LARS artificial ligaments had a florid foreign body reaction. There was minimal tissue ingrowth in ACL grafts and moderate ingrowth in other grafts. Retrieved grafts had a decreased ultimate tensile force, which increased their risk of rupture. Surgeons should be cautious in choosing to use these grafts in reconstructive surgery for patients.

Application and Development of Electrospun Nanofiber Scaffolds for Bone Tissue Engineering.

Nanofiber scaffolds have gained significant attention in the field of bone tissue engineering. Electrospinning, a straightforward and efficient technique for producing nanofibers, has been extensively researched. When used in bone tissue engineering scaffolds, electrospun nanofibers with suitable surface properties promote new bone tissue growth and enhance cell adhesion. Recent advancements in electrospinning technology have provided innovative approaches for scaffold fabrication in bone tissue engineering. This review comprehensively examines the utilization of electrospun nanofibers in bone tissue engineering scaffolds and evaluates the relevant literature. The review begins by presenting the fundamental principles and methodologies of electrospinning. It then discusses various materials used in the production of electrospun nanofiber scaffolds for bone tissue engineering, including natural and synthetic polymers, as well as certain inorganic materials. The challenges associated with these materials are also described. The review focuses on novel electrospinning techniques for scaffold construction in bone tissue engineering, such as multilayer nanofibers, multifluid electrospinning, and the integration of electrospinning with other methods. Recent advancements in electrospinning technology have enabled the fabrication of precisely aligned nanofiber scaffolds with nanoscale architectures. These innovative methods also facilitate the fabrication of biomimetic structures, wherein bioactive substances can be incorporated and released in a controlled manner for drug delivery purposes. Moreover, they address issues encountered with traditional electrospun nanofibers, such as mechanical characteristics and biocompatibility. Consequently, the development and implementation of novel electrospinning technologies have revolutionized scaffold fabrication for bone tissue engineering.

Light-controlled crosslinked multifunctional "Band-Aids" as dual-stage wound dressing for dynamic wound closure

The objective of regenerative wound healing dressings is to accelerate skin tissue regeneration and restore normal physiological function at wound sites. Achieving this goal requires biomaterials capable of repairing distinct phases of wound healing in a way that balances material function, degradation, safety, and tissue growth. In this study, we introduced a novel dual-stage wound dressing system comprising methacrylic anhydride-modified recombinant humanized type III collagen (rhCol III-MA) and methacrylic anhydride-modified dopamine (DMA) (RMDM), which was synthesized through free radical polymerization and π-π stacking. Within this system, RMDM was formulated into two forms with identical compositions: hydrogel and sponge, tailored for application across various stages of wound repair. These materials displayed favorable hemocompatibility, biocompatibility, antioxidant properties, and angiogenic potential in vitro. Moreover, the in vivo experiments also demonstrated that sponges could rapidly stop the bleeding of wounds in mouse tail amputation and liver incision models. Notably, the sponge/gel (S/G) system accelerated wound healing compared to individual sponge and gel treatments in a rat full-thickness skin wound model, underscoring the synergistic benefits of combining sponge and gel materials for wound repair at different stages. Therefore, this research provides valuable insights into designing advanced biomaterials that can be tailored to specific stages of wound healing, which may have significant potential for biomedical applications.Graphical

A Review of Cartilage Defect Treatments Using Chitosan Hydrogels in Experimental Animal Models.

Chitosan (CS) is a polycationic polysaccharide comprising glucosamine and N-acetylglucosamine and constitutes a potential material for use in cartilage tissue engineering. Moreover, CS hydrogels are able to promote the expression of cartilage matrix components and reduce inflammatory and catabolic mediator production by chondrocytes. Although all the positive outcomes, no review has analyzed the effects of CS hydrogels on cartilage repair in animal models. This study aimed to review the literature to examine the effects of CS hydrogels on cartilage repair in experimental animal models. The search was done by the descriptors of the Medical Subject Headings (MeSH) defined below: "Chitosan," "hydrogel," "cartilage repair," and "in vivo." A total of 420 articles were retrieved from the databases Pubmed, Scopus, Embase, Lilacs, and Web of Science. After the eligibility analyses, this review reported 9 different papers from the beginning of 2002 through the middle of 2022. It was found that cartilage repair was improved with the treatment of CS hydrogel, especially the one enriched with cells. In addition, CS hydrogel produced an upregulation of genes and proteins that act in the cartilage repair process, improving the biomechanical properties of gait.. In conclusion, CS hydrogels were able to stimulate tissue ingrowth and accelerate the process of cartilage repair in animal studies.

The Protective Effects of Acteoside and Total Glycosides of the Leaves of Rehmannia on Three Types of Glomerular Structural Cells Under High Glucose and Inflammatory Stimulation

ABSTRACT Background: The challenge of chronic glomerulonephritis necessitates innovative strategies for preventing renal function deterioration. Acteoside (ACT), the primary bioactive compound of total glycosides of the leaves of Rehmannia (DHYZG), has been demonstrated availability and safety in reducing proteinuria, showing promising prospects in the treatment of kidney disease. This study aimed to elucidate the impact of ACT and DHYZG on glomerular structural cells and key proteins of rat glomeruli under several injury states. Methods: Employing 3-(4,5)-dimethylthiazolyl(-Z-Y1)-3,5-diphenyltetrazolium bromide (MTT) and Western blot methodologies, the investigation assessed varying concentrations of ACT and clinical concentration of DHYZG on cell viability and intracellular biomarkers. Specifically, the study explored the influence of ACT on connective tissue growth factor (CTGF), transforming growth factor-β (TGF-β), matrix metalloproteinase-2 (MMP-2), and MPP in rat mesangial cells, endothelial cells, and podocytes stimulated by lipopolysaccharide (LPS), high glucose, and interleukin-1β (IL-1β). Additionally, the impact of high glucose on angiotensin II (Ang II) expression in endothelial cells was investigated. Results: ACT and DHYZG demonstrated a protective effect on all cell types, and ACT administration shows a significant dose-dependent response. These compounds attenuated the expression of CTGF and TGF-β in LPS-stimulated mesangial cells and reduced the expression of MMP-2 and MMP-9 in all three cell types following IL-1β stimulation. Moreover, the high glucose-induced expression of Ang II in endothelial cells was mitigated. Conclusion: ACT and DHYZG exhibit a pronounced protective effect on glomerular cells, with ACT being the primary contributor to the therapeutic efficacy of DHYZG. Notably, ACT demonstrates a significant superiority over DHYZG in terms of both proliferation and cytokine expression in glomerular endothelial cells.

Non-isocyanate polyurethane-co-polyglycolic acid electrospun nanofiber membrane wound dressing with high biocompatibility, hemostasis, and prevention of chronic wound formation

The prevention of chronic wound formation has already been a primary subject in wound management, particularly for deep wounds. The electrospun nanofiber membranes hold tremendous potential in the prevention of chronic wounds due to their micro/nano pore structures. Currently, many natural and synthetic materials have been utilized in the fabrication of nanofiber membranes. However, striking a balance between the structural stability and the biocompatibility remains challenging. It is necessary not only to ensure the long-term durability of nanofiber membranes but also to enhance their biocompatibility for alleviating patients' suffering. In this study, we reported a nanofiber membrane dressing with excellent biocompatibility and mechanical properties, which is potential for the treatment of deep wounds. The basal material chosen for the preparation of the nanofiber membrane was a co-polyester (NI-LPGD5) synthesized by non-isocyanate polyurethane (NIPU) and polyglycolic acid with a dihydroxy structure (LPGD—synthesized from glycolic acid and neopentyl glycol). Moreover, curcumin was also added as a bioactive substance to enhance the pro-healing effect of dressings. The physicochemical properties of the prepared nanofiber membranes were characterized through various physicochemical tools. Our results demonstrated that the NI-LPGD5 co-polymer can be electrospun into smooth fibers. Meanwhile, curcumin-loaded nanofiber membranes (Cur/NI-LPGD5) also exhibited a favorable microscopic morphology. The fabricated membranes exhibited suitable mechanical properties, outstanding hygroscopic-swelling rate and water vapor transmittance. Besides, in vitro cell culturing, the cells on the NI-LPGD5 membrane maintained their maximum viability. The potential of in vivo wound healing was further demonstrated through animal experiments. The experimental results showed that the nanofiber membranes effectively prevented chronic wounds from forming and promoted granulation tissue growth without replacing the dressing throughout the healing process. We also found that these nanofiber membranes could effectively promote the expression of related biomarkers to accelerate wound healing, particularly the Cur/NI-LPGD5 membrane. In conclusion, the fabricated membranes possess suitable physicochemical properties and promising bioactivity. As a result, it effectively prevented the formation of chronic wounds and demonstrated significant potential in reducing the frequency of dressing changes.

Structural characteristics of wheat bran insoluble dietary fiber with various particle size distributions and their influences on the kinetics of gastrointestinal emptying in mice

Wheat bran is an abundant yet underutilized agricultural byproduct. Herein, the insoluble dietary fiber from wheat bran (WBIDF) was ultra-milled to investigate its impact on physicochemical properties and gastrointestinal emptying. SEM and CLSM showed that the laminar structure of WBIDF was disrupted as the particle size was significantly reduced. In the similar characteristic peaks appearing at 3410, 2925, 1635, 1041, and 895 cm−1 in the FT-IR spectra and at 2940, 1593, 1080, and 526 cm−1 in the Raman spectra, the peak intensity was increased as the particle size decreased. It may be that the hydrogen bonding between cellulose, hemicellulose, or other macromolecules was enhanced. X-ray diffraction showed cellulose type I results for all five samples. Correspondingly, the water-holding, swelling, and oil-holding capacities increased by 75.33 %, 52.62 %, and 75.00 %, respectively, in WBIDF-CW1.8 compared with WBIDF-CWy. Additionally, smaller particle sizes had lower viscosity, thereby enhancing intestinal propulsion and gastric emptying rates. Enhanced contact of the cecal tissue growth factor with the intestinal mucosa delayed ghrelin secretion and stimulated the secretion of motilin, gastrin, and cholecystokinin. In conclusion, the particle sizes of WBIDF were reduced through ultramicro-grinding, leading to altered structure, enhanced hydration and oil-holding capacities, decreased viscosity, and improved gastrointestinal emptying capacity.

Melorheostosis (Leri's Disease): A Review.

Melorheostosis is a noncancerous bone disease characterized by abnormal bone and soft tissue growth. Despite being identified almost a century ago, there are still many unknown aspects surrounding this condition. It can often be an incidental discovery, with patients experiencing associated pain and deformities. Diagnosis typically relies on X-rays, although not all cases exhibit the classic candle wax appearance. A new imaging sign known as the "dumpling on a plate sign" has been proposed for flat bones for both MRI and CT scans. A biopsy may be necessary in cases of uncertainty, as there is not a definitive histological feature. It is not uncommon for melorheostosis to be linked with other conditions, and a collaborative approach involving a multidisciplinary team should be considered. This condition should be considered in the differential diagnosis of sclerotic bone conditions. Management is generally aimed at symptom relief, either through conservative measures or surgical intervention.

Sprayable hydrogel with optical mRNA nanosensors for Real-Time monitoring and healing of diabetic wounds

Sprayable hydrogels offer a promising approach for treating diabetic wounds. They possess the capability to conform to irregular surfaces, create a moist environment that supports the growth of new tissue, and offer protection against infections. Yet, applying previously reported sprayable hydrogels has proven to be challenging, often necessitating the use of specialized equipment or the simultaneous injection of multiple components. In this study, we develop a user-friendly therapeutic hydrogel that can be applied using a general spray bottle. This hydrogel is formulated using the bioactive agent, LL37, which is known for its antimicrobial properties and ability to enhance angiogenesis. Additionally, optical mRNA nanosensors, NanoFlares, were incorporated into the hydrogel to measure the expression of proliferation and inflammation biomarkers, providing precise molecular-based parameters for evaluating diabetic wound status. The efficacy of LL37- and NF-incorporated hydrogels in promoting in vivo wound healing in normal and diabetic mice is evaluated, and a Wound Healing Index (WHI) is presented to assist medical professionals in making informed decisions about wound care and treatment. Overall, our study demonstrates the potential of sprayable hydrogels for promoting diabetic wound healing and monitoring the diabetic wound status, which could have significant potential for future clinical applications.

Myogenesis of Porcine Muscle Satellite Cells by Extracellular Matrix From Fibrotic Adipose Tissue-Derived Mesenchymal Stem Cells

Cultivated meat relies on the production of muscle tissue using cell culture techniques. Myogenesis is a cellular differentiation process in which muscle satellite cells (SC) transform into myoblasts, or myotubes. The extracellular matrix (ECM) plays a pivotal role in meat quality, myogenesis, SC proliferation, and muscle tissue development to replicate meat texture. Because fibrotic differentiation and ECM are involved in the myogenic process, we aimed to induce myogenesis in SC using fibrotic differentiation of adipose tissue-derived mesenchymal stem cells (ADSC). ADSC, fibroblasts (FC), and SC were isolated from the back fat, ear margin tissues, and femur muscle tissues, respectively, of a 1-year-old Berkshire piglet. ADSC were treated with connective tissue growth factor (CTGF; 0, 12.5, 25, or 50 ng/mL) for 72 h to induce fibrotic differentiation. Conditioned media from differentiated ADSC and FC were prepared and labeled CA-CM and F-CM, respectively. SC were exposed to CA-CM or F-CM to assess their effects on myogenesis. The results demonstrated &amp;alpha;-smooth muscle actin and collagen I as the optimal markers for assessing fibrotic differentiation in ADSC. CTGF significantly elevated both mRNA and protein expression of &amp;alpha;-smooth muscle actin and collagen I (P &amp;lt; 0.05), suggesting that CTGF acts as an inducer of fibrotic differentiation in ADSC. Moreover, CTGF elevated the expression of ECM components (laminin, fibronectin, and collagen I) in ADSC (P &amp;lt; 0.05). mRNA expression of myogenesis-related genes (MyoG, MyoD, Myf5, and Myf6) increased in SC exposed to both CA-CM and F-CM (P &amp;lt; 0.05). Our data revealed that fibrotic differentiation of ADSC increased ECM production, and ECM-containing conditioned medium induced myogenesis in SC. These findings indicate that ECM-containing conditioned medium is a good option for enhancing myogenesis in SC, with potential implications for cultivated meat production.

Miniaturized all-in-one microneedle device for point of care light therapy

Light therapies have been applied to millions of patients for treating many kinds of diseases, especially superficial ones. Currently, mainstream light therapies utilize the combined effects of photosensitizers and light to either remove disordered tissue or promote the growth of healthy tissue. Adverse effects of light therapy, including metabolic burden caused by circulatory photosensitizer and skin damage induced by high irradiance light, are yet to be addressed. This study provides a Miniaturized all-in-one Light therapy Device (MiLD). All components required for light therapy, including dual-function microneedles, LED array, control circuit, and battery are integrated together to form a miniaturized portable device with 2 cm in length, 1.7 cm in width, 1.2 cm in height, and 3.6 g in weight. The all-in-one design and patch-to-cure operation of MiLD enables the successful demonstration of point-of-care light therapy. Satisfactory therapeutic effects have been verified in mice on both types of light therapy. Meanwhile, transdermally co-delivering both photosensitizer and light in situ fully avoids photosensitizer accumulation in blood and remarkably reduces the irradiance of light, therefore significantly alleviating metabolic burden and light-induced skin damage. Overall, the MiLD lays the technical foundation of point-of-care light therapy with its miniaturized all-in-one design, simple patch-to-cure operation, satisfactory therapeutic effects, and minimum adverse effects.

BRAIN TUMOR DETECTION USING MACHINE LEARNING

A brain tumor is the cause of abnormal growth of cells in the brain. Magnetic resonance imaging (MRI) is the most practical method for detecting brain tumors. Through these MRIs, doctors analyze and identify abnormal tissue growth and can confirm whether the brain is affected by a tumor or not. Today, with the emergence of artificial intelligence techniques, the detection of brain tumors is done by applying the techniques and algorithms of machine learning and deep learning. The advantages of the application of these algorithms are the quick prediction of brain tumors, fewer errors, and greater precision, which help in decision-making and in choosing the most appropriate treatment for patients. In the proposed work, a convolution neural network (CNN) is applied with the aim of detecting the presence of a brain tumor and its performance is analyzed. The main purpose of this article is to adopt the approach of convolutional neural networks as a machine learning technique to perform brain tumor detection and classification. Based on training and testing results, the pre- trained architecture model reaches 96% in precision and classification accuracy rates. For the given dataset, CNN proves to be the better technique for predicting the presence of brain tumors. Keywords—Brain tumor; machine learning; convolutional neural network; MRI images

Effect of collagen sponge combined with epidermal growth factor in repairing maxillofacial head and neck wounds in rats.

Collagen sponge and epidermal growth factor (EGF) promote wound healing. However, the effect of collagen sponge combined with EGF in repairing maxillofacial head and neck wounds remains unclear. The rats were divided into 3 groups, including experimental group 1 (Vaseline gauze+EGF), experimental group 2 (collagen sponge+EGF) with control group (Vaseline+normal saline), and maxillofacial head and neck wounds were simulated. Wound pathological morphology was detected by HE staining; wound EGF, IL-1β, IL-6 along with TNF-α contents by ELISA and MMP1 level by western blot. At 7 and 14 days after treatment, wound healing rate of two experimental groups was higher than that of control group, and that of experimental group 2 presented higher than that of experimental group 1. Compared with control group, experimental group 1 had significantly fewer inflammatory cells in the wound tissue, local erythrocyte spillage outside the vascular walls, more collagen deposition and more granulation tissue. Compared with experimental group 1, inflammatory cells in wound tissues of experimental group 2 were significantly reduced, the collagen tissues were visible and arranged, and the growth of the wound granulation tissue was obvious. IL-1β, IL-6 along with TNF-α levels in two experimental groups presented lower than control group, and EGF level was higher. More importantly, in contrast to experimental group 1, IL-1β, IL-6 along with TNF-α in experimental group 2 presented lower, and EGF level presented higher. At 14 days after treatment, MMP1 level in two experimental groups was lower than control group. In contrast to experimental group 1, MMP1 level in experimental group 2 was lower. In summary, collagen sponge combined with EGF for the first time significantly improved the healing speed of maxillofacial head and neck wounds and reduced the scar left after wound healing.

Coatings for Permanent Meshes Used to Enhance Healing in Abdominal Hernia Repair: A Scoping Review.

Hernia meshes are used to reduce recurrence and pain rates, but the rates are still high. This could be improved with coatings of the mesh. This scoping review aimed to provide an overview of mesh coatings used to promote healing in abdominal hernia repair and to report beneficial and unbeneficial effects. We included human and animal studies with abdominal hernias that were repaired with non-commercially coated meshes. We searched Pubmed, Embase, Cochrane Central, LILACS, and CNKI without language constraints. Of 2933 identified studies, 58 were included: six studies had a total of 408 humans and 52 studies had 2679 animals. The median follow-up was 12 months (range 1-156), and 95% of the hernias were incisional. There were 44 different coatings which included platelet-rich plasma, mesenchymal stem cells, growth factors, vitamin E, collagen-derived products, various polysaccharides, silk proteins, chitosan, gentamycin, doxycycline, nitrofurantoin, titanium, and diamond-like carbon. Mesenchymal stem cells and platelet-rich plasma were the most researched. Mesenchymal stem cells notably reduced inflammation and foreign body reactions but did not impact other healing metrics. In contrast, platelet-rich plasma positively influenced tissue ingrowth, collagen deposition, and neovascularization and had varying effects on inflammation and foreign body reactions. We identified 44 different mesh coatings and they showed varying results. Mesenchymal stem cells and platelet-rich plasma were the most studied, with the latter showing considerable promise in improving biomechanical properties in hernia repair. Further investigations are needed to ascertain their definitive use in humans.

Design and Additive Manufacturing of Nerve Guide Conduits Using Triple Periodic Minimal Surface Structures

Scaffold design is a key study area in tissue engineering. A scaffold is a three-dimensional framework that provides temporary support for the formation of new tissue before being implanted with isolated cells. The aim of tissue engineering scaffolds is to be colonized by cells. To ensure sufficient tissue growth, scaffolds need to transmit the necessary chemical and physical signals. The design of the scaffold determines its functionality. The design and manufacturing of tissue engineering scaffolds is a highly complex procedure. Scaffolds must have the necessary qualities to create an optimal architecture for cell growth, proliferation, and differentiation in order to form tissue. However, constrained structural designs and outdated manufacturing procedures impede the enhancement of scaffold qualities. To address these restrictions, researchers are merging computer-aided scaffold design with 3D printing processes during production. This method permits the design and manufacture of scaffolds with extremely intricate microstructures. The literature shows that computer-aided design combined with 3D printing technology is often utilized to design and manufacture nerve guide conduits for nerve regeneration. In this study, three different nerve guide conduit structures were designed and produced. Two of them are based on triple periodic minimal surfaces derived from Gyroid, schwarz. Although triple periodic minimal surfaces used as the basis for scaffold designs offer promising advantages for tissue engineering applications, limited information is available regarding their manufacturability. The designs created in this study, as well as their fabrication, will add to the literature on the manufacturability of triple periodic minimum surfaces.

The regulatory effect of electroacupuncture on endometrial M1-type macrophages in rats with intrauterine adhesions.

To observe the effect of electroacupuncture(EA) on endometrial fibrosis and M1-type macrophages in rats with intrauterine adhesions(IUA), so as to explore the possible mechanism of EA in the treatment of IUA. Fifteen female SD rats were randomly divided into blank group, model group and EA group, with 5 rats in each group. The IUA rat model was established by double damage method using mechanical scraping combined with lipopolysaccharide infection. Rats in the EA group were treated with acupuncture at "Guanyuan"(CV4), and EA at bilateral "Zusanli"(ST36) and "Sanyinjiao"(SP6)for 20 minutes each time, once a day, for 3 consecutive cycles of estrus. Five rats in each group were sampled during the estrous period, and the endometrial morphology, endometrial thickness and the number of blood vessels and glands were observed after HE staining. The fibrotic area of the uterus was observed after Masson staining. The positive expressions of Runt-related transcription factor(RUNX1), transforming growth factor-β1(TGF-β1), connective tissue growth factor(CTGF), α-smooth muscle actin(α-SMA), collagen type I(Col-Ⅰ), cluster of differentiation 86(CD86), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) in endometrial tissue were detected by immunohistochemistry. Western blot was used to detect relative protein expressions of RUNX1, TGF-β1, α-SMA, CD86, and TNF receptor 2 (TNFR2), and real-time fluorescence quantitative PCR was used to detect mRNA expressions of RUNX1, TGF-β1, α-SMA, CD86, and TNF-α in the endometrium. During the estrous phase, the endometrial layer in the model group was damaged, with reduced folds, disordered arrangement of epithelial cells, loose fibrous connective tissue, significant narrowing and adhesions in the uterine cavity, interstitial congestion, edema, and a significant infiltration of inflammatory cells with sparse glands. While uterine tissue structure of the EA group was basically intact, resembling a normal uterus, with more newly formed glands and a small amount of inflammatory cell infiltration. In comparison with the blank group, the endometrial thickness, the number of blood vessels, and the number of glands were significantly decreased(P<0.001) in the model group, while the ratio of uterine fibrosis area, the positive expressions of RUNX1, TGF-β1, CTGF, α-SMA, Col-Ⅰ, CD86, IL-1β, and TNF-α, the protein relative expressions of RUNX1, TGF-β1, α-SMA, CD86 and TNFR2, and the mRNA relative expression levels of RUNX1, TGF-β1, α-SMA, CD86 and TNF-α in the endometrium were significantly increased (P<0.001, P<0.01). Compared to the model group, the endometrial thickness, the number of blood vessels, and the number of glands were significantly increased(P<0.01, P<0.05) in the EA group, while the ratio of uterine fibrosis area, the positive expressions of RUNX1, TGF-β1, CTGF, α-SMA, Col-Ⅰ, CD86, IL-1β and TNF-α in the endometrial tissue, the protein expressions of RUNX1, TGF-β1, α-SMA, CD86 and TNFR2, and the mRNA relative expressions of RUNX1, TGF-β1, α-SMA, CD86 and TNF-α in the endometrium were significantly decreased (P<0.001, P<0.01, P<0.05). EA can improve endometrial fibrosis in IUA rats, which may be related to its function in decreasing the level of endometrial M1-type macrophages and the secretion of related inflammatory factors.

Intratracheal instillation of polyacrylic acid induced pulmonary fibrosis with elevated transforming growth factor-β1 and connective tissue growth factor

We investigated the intratracheal instillation of Polyacrylic acid (PAA) in rats to determine if it would cause pulmonary disorders, and to see what factors would be associated with the pathological changes. Male F344 rats were intratracheally instilled with low (0.2 mg/rat) and high (1.0 mg/rat) doses of PAA. They were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months after PAA exposure to examine inflammatory and fibrotic changes in the lungs. There was a persistent increase in the neutrophil count, lactate dehydrogenase (LDH) levels, cytokine-induced neutrophil chemoattractant (CINC) values in bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in lung tissue. Transforming growth factor-beta 1 (TGF-β1), a fibrotic factor, showed a sustained increase in the BALF until 6 months after intratracheal instillation, and connective tissue growth factor (CTGF) in lung tissue was elevated at 3 days after exposure. Histopathological findings in the lung tissue showed persistent (more than one month) inflammation, fibrotic changes, and epithelial-mesenchymal transition (EMT) changes. There was also a strong correlation between TGF-β1 in the BALF and, especially, in the fibrosis score of histopathological specimens. Intratracheal instillation of PAA induced persistent neutrophilic inflammation, fibrosis, and EMT in the rats’ lungs, and TGF-β1 and CTGF appeared to be associated with the persistent fibrosis.

Paeoniflorin alleviates TGF-β2-mediated extracellular matrix remodeling and oxidative stress in human trabecular meshwork cells.

The multifunctional profibrotic cytokine transforming growth factor-beta2 (TGF-β2) is implicated in the pathophysiology of primary open angle glaucoma. Paeoniflorin (PAE) is a monoterpene glycoside with multiple pharmacological efficacies, such as antioxidant, anti-fibrotic, and anti-inflammatory properties. Studies have demonstrated that paeoniflorin protects human corneal epithelial cells, retinal pigment epithelial cells, and retinal microglia from damage. Here, the biological role of PAE in TGF-β2-dependent remodeling of the extracellular matrix (ECM) within the trabecular meshwork (TM) microenvironment. Primary or transformed (GTM3) human TM (HTM) cells conditioned in serum-free media were incubated with TGF-β2 (5ng/mL). PAE (300μM) was added to serum-starved confluent cultures of HTM cells for 2h, followed by incubation with TGF-β2 for 22h. SB-431542, a TGF-β receptor inhibitor (10μM), was used as a positive control. The levels of intracellular ROS were evaluated by CellROX green dye. Western blotting was used to measure the levels of TGF-β2/Smad2/3 signaling-related molecules. Collagen 1α1, collagen 4α1, and connective tissue growth factor (CTGF) expression was evaluated by RT-qPCR. Immunofluorescence assay was conducted to measure collagen I/IV expression in HTM cells. Phalloidin staining assay was conducted for evaluating F-actin stress fiber formation in the cells. PAE attenuated TGF-β2-induced oxidative stress and suppressed TGF-β2-induced Smad2/3 signaling in primary or transformed HTM cells. Additionally, PAE repressed TGF-β2-induced upregulation of collagen 1α1, collagen 4α1, and CTGF expression and reduced TGF-β2-mediated collagen I/IV expression and of F-actin stress fiber formation in primary or transformed HTM cells. PAE alleviates TGF-β2-induced ECM deposition and oxidative stress in HTM cells through inactivation of Smad2/3 signaling.