Growth Factor bFGF Research Articles

Testicular Cells Derived Conditioned Medium Supports Germ Cell Differentiation of Human Embryonic Stem Cells.

There are ethical and technical challenges in studying human germ cell development. Therefore, the aim of the study is in vitro differentiation of human embryonic stem cells (hESCs), as pluripotent cells, to the germ cells which is a valuable tool for studying molecular and cellular aspects of gametogenesis and understanding causes of infertility. In this experimental study, two different complete media [Dulbecco's Modified Eagle Medium (DMEM)+20% fetal bovine serum (FBS) and embryoid bodies (EBs) medium; KOSR/HES without basic fibroblast growth factor (bFGF)] were used in the both of test groups using testicular cells derived conditioned medium (TCCM) and control groups spontaneously differentiated (SD). Thereby, EBs from hESCs (Yazd2; 46XY) were cultured in different conditions EB medium; EB medium and conditioned EB medium; EB medium, DMEM, and FBS without conditioning; EB medium, conditioned DMEM, and FBS medium. EBs were collected after 4, 7, and 14 days and their gene expression profiles were assessed and compared to hESCs, as day 0, using IF and relative reverse transcription quantitative polymerase chain reaction (RT-qPCR). An increase in the gametogenesis gene expression level in TCCM groups was showed in comparison with SD groups. Additionally, immunostaining of differentiated cells in all groups showed in vitro gametogenesis (IVG). Our findings showed that human TCCM could be used as a natural niche for in vitro male and female germ cell development. However, further studies are needed to define the factors and metabolites within the human TCCM.

Design and decoration of copper nanoparticles into lignosulfonate-starch bionanocomposite: Characterization and evaluation of its therapeutic properties on burn wound

In this report, eco-friendly synthesis for the production of copper nanoparticles by employing the sodium lignosulfonate (NaLS) mixed starch composite (NaLS-Starch/Cu NPs). NaLS-Starch mixed hydrogel has notable reducing and stabilizing potential for preparation of Cu nanoparticles. Characterization of NaLS-Starch/Cu NPs bionanocomposite was subjected to analysis of spectroscopic and microscopic techniques, including FE-SEM, TEM, EDS-elemental mapping, particle size distribution, XRD and ICP. TEM images displayed the spherical structured NaLS-Starch/Cu NPs, averaging 5–10 nm size. NaLS-Starch/Cu NPs were applied to cure the induced burn wounds in 60 Wistar rats. A group was considered as control group. The animals were treated with basal, tetracycline 3 % and NaLS-Starch/Cu NPs 3 % for 30 days and the treatment efficacy was determined according to the burn wound area reduction and molecular and histological characteristics. Taken together, these results support therapeutic use of NaLS-Starch/Cu NPs as potent ointment that may be proposed for burn wound healing. NaLS-Starch/Cu NPs ointment increased the levels of platelet-derived growth factors (PDGF) and fibroblast growth factor (bFGF). The mean wound surface, in all groups treated by NaLS-Starch/Cu NPs was larger than control group.

Chondrocyte Response to Fresh Autologous Conditioned Serum Versus Freeze-Dried Allogenic Conditioned Serum.

To investigate the cytokine release profile and histological response of human cartilage after exposure to autologous conditioned serum (ACS) and freeze-dried allogenic conditioned serum (FD-CS). Cartilage explants were collected from 6 patients undergoing total knee arthroplasty. ACS and FD-CS were created from patient serum samples. Cartilage samples were divided into 6 groups: (1) untreated control, (2) ACS, (3) FD-CS, (4) untreated interleukin (IL)-1β (5 ng/ml), (5) IL-1β + ACS, and (6) IL-1β + FD-CS. After 12 days, cartilage samples were analyzed with glycosaminoglycan (GAG) concentration normalized to wet weight while comparing cytokine concentrations, and histological scoring. There was a significant decrease in pathology scoring for ACS (P = 0.0368) and FD-CS (P = 0.0368) in the IL-1β injury groups compared with the untreated IL-1β insult group. ACS and FD-CS significantly mitigate the IL-1β induced increase in basic fibroblast growth factor (bFGF) (P = 0.0009 and P = 0.0002, respectively). FD-CS showed a significant decrease in IL-1β concentration in the presence of IL-1β insult compared with the untreated IL-1β group (P < 0.0001). ACS-treated samples had significantly higher concentration of tumor necrosis factor (TNF)-α independent of IL-1β when compared with samples not treated with biologics (P = 0.0053). Explanted osteoarthritic cartilage responds favorably and equivalently to treatment with ACS and FD-CS from a histological perspective. Both ACS and FD-CS were able to mitigate the IL-1β-induced increases in bFGF and FD-CS lowered IL-1β concentration while increasing interleukin-1 receptor antagonist (IL-1Ra) concentration. Although the cytokine profile of cartilage tissue explants treated with FD-CS appears to be different than that of ACS, this difference does not seem to affect biologic activity of FD-CS.

Healing mechanism of cotton bandages loaded with PNIPAM/GO-Ag hydrogel on deep second-degree burn wounds in a rat model

Dressings play a crucial role in the management of burn wounds. In this study, cotton bandages were modified with poly (N-isopropylacrylamide)/graphite oxide/nano silver (PNIPAM/GO-Ag) hydrogel to obtain a novel dressing (PNIPAM/GO-Ag/COT). The healing effect of the PNIPAM/GO-Ag/COT dressing on deep second-degree burn wounds in rats and the changes of related inflammatory factors were explored and analyzed systematically. The deep second-degree burn model was established by the steam scald method in Sprague–Dawley (SD) rats. The granulation tissue, collagen deposition, the expression of tumor necrosis factor-α (TNF-α), and basic fibroblast growth factor (bFGF) in the wound were evaluated by means of HE staining, Masson staining, ELISA, and immunohistochemistry methods. The results showed that, compared with the blank group (rats without the dressing treatment), the PNIPAM/GO-Ag/COT dressing reduced the expression of TNF-α by approximately 18 % and promoted the bFGF expression in wound tissue. Compared to the control group (rats with the gauze treatment), the wound healing rate in the PNIPAM/GO-Ag/COT dressing group was 58 % on the 14th day, with an increase of 30 %. These results demonstrated that the PNIPAM/GO-Ag/COT dressing primarily promoted burn wound healing by reducing inflammatory reactions, promoting collagen deposition, and enhancing the expression of bFGF.

Study on the effect and mechanism of Yanghe decoction Huacai on tissue repair ofsyndrome after anal fistula surgery.

To observe the clinical efficacy and safety of Yanghe decoction Huacai for the repair of Yin syndrome wounds with slow-healing after anal fistula surgery. A total of 120 patients with slow-healing negative wounds with after low-grade anal fistula surgery who met the inclusion criteria were divided into a treatment group and a control group based on a random number table method, with 60 patients in the treatment group and 60 patients in the control group. The treatment group was given Yanghe decoction Huacai in combination with routine treatment; the control group was only given routine treatment, in which the wound surface was disinfected with iodine, and then covered with sterile gauze. The course of treatment in both groups was 10 d. After treatment, the wound secretion score, wound granulation tissue score, the expression levels of basic fibroblast growth factor (bFGF), transforming growth factor β1 (TGF-β1), and epidermal growth factor (EGF) in the wound, wound healing time and clinical efficacy were compared. There was no significant difference in age or gender between the two groups (P > 0.05). On the 10th and 15th days after the surgery, the wound secretion scores were higher in the treatment group than in the control group (P < 0.01). Comparing the two groups at the 10th and 15th day after surgery, the granulation tissue growth scores in the treatment group were better than the in control group (P < 0.01). On the 10th and 15th day after operation, the expression levels of bFGF, TGF-β1 and EGF factors in the treatment group were stronger than those in the control group. The healing time of the wounds in the treatment group was significantly shorter than in the control group (P < 0.01). The clinical efficacy of the two groups after treatment was compared, and the overall efficacy of the treatment group was significantly higher than that of the control group (P < 0.01). Yanghe decoction Huacai have significant efficacy in the treatment of slow-healing wounds with Yin syndrome after anal fistula surgery. It improves wound secretions, promotes the growth of wound granulation tissue, and shortens wound healing time. Its mechanism of action may be related to the control of wound inflammation. It is related to increasing the expression of bFGF, TGF-β1 and EGF in wound tissue, and promoting wound angiogenesis and fibroblast proliferation.

Optimization of Vascularized Intestinal Organoid Model.

Vasculature is crucial for maintaining organ homeostasis and metabolism. Although 3D organoids can mimic organ structures and patterns, they still lack vascular systems, limiting the recapitulation ofphysiological complexities. Although vascularization of organoids has been demonstrated by mixing Matrigel in fibrin, how the mixed gel niche affects endothelial cells (ECs) and organoids remains unclear. Existing protocols rely on fibroblasts to promote vascular network formation. This study explores how varying the ratio of Matrigel in fibrin-Matrigel co-gel affects vascular network formation and intestinal organoid growth.A fine-tuned hydrogel is developed by adding aprotinin and 15% Matrigel in fibrin. Medium for co-culturing ECs and organoids is modified with basic fibroblast growth factor (bFGF) and heparin. In combination with fine-tuned hydrogel and modified medium, vascular network formation and organoid vascularization are successfully generated in the absence of fibroblast. Furthermore, structural cues and pore architectures are critical for angiogenesis and vascularization. By incorporating engineered thick collagen fiber bundles into the system, vascular network formation is guided by bundle architectures, enhancing interactions between vascular networks and organoids. The results demonstrate an optimized system that advances tissue and organoid vascularization by combining fiber bundles with fine-tuned hydrogel and modified medium.

Basic Fibroblast Growth Factor Supports the Function of Limbal Niche Cells via the Wnt/β-Catenin Pathway.

Purpose: To test the effects and underlying mechanisms of basic fibroblast growth factor (bFGF) on the limbal niche cell (LNC) function ex vivo. Methods: By using different concentrations of bFGF (0, 4, 8, 12, and 16 ng/mL) and fibroblast growth factor receptor (FGFR) inhibitors, the effects of bFGF on LNC proliferation, expression of stem cell markers, and transcription levels of the β-catenin were investigated. Single-cell RNA sequencing (scRNA-seq) was used to analyze the action and mechanisms of FGFR subtypes and the Wnt/β-catenin pathway during LNC culture. An mature corneal epithelial cell (MCEC)/LNC three-dimensional model was constructed to verify whether bFGF activates the Wnt/β-catenin pathway in LNC by inhibiting FGFR or β-catenin targets. Results: scRNA-seq showed that FGFR1 is the main receptor in LNC, along with the molecules in the Wnt pathway, including WNT2, FZD7, LRP5, LRP6, and β-catenin. The 12 ng/mL bFGF treatment group showed higher LNC proliferation rate and transcription levels of OCT4, SOX2, NANOG, and β-catenin than any other groups (P < 0.001). In the MCEC/LNC co-culture model, MCEC/LNC treated with 12 ng/mL bFGF promoted the aggregation of the spheres than other groups, associated with increased transcription levels of P63α, WNT2, β-catenin, and a decreased transcription level of CK12 (P < 0.001). Wnt/β-catenin inhibitor LF3 treatment reversed the abovementioned effect of bFGF. Conclusions: bFGF could maintain and promote the stemness of LNC via the FGFR1/Wnt2/FZD7/LRP6 axis in a concentration-dependent manner.

Causal effects of inflammatory cytokines on cardiovascular diseases: Insights from genetic evidence

BackgroundThe causal relationship between inflammatory cytokines and cardiovascular diseases (CVDs) has not been fully elucidated. Exploring this relationship between circulating inflammatory cytokines and CVDs is crucial for early clinical diagnosis and effective treatment. Methods and ResultsThis study investigated the causal relationships between 41 inflammatory cytokines and six CVDs: heart failure (HF), myocardial infarction (MI), unstable angina pectoris (UAP), stable angina pectoris (SAP), valvular heart disease (VHD), and aortic aneurysm (AA), using the Mendelian Randomization (MR) method. The primary analysis employed the inverse-variance weighted (IVW) method within MR. Heterogeneity and pleiotropy were assessed through MR-Egger regression and the Q statistic. Strong evidence supported the effect of macrophage inflammatory protein-1β (MIP-1β) on MI (OR = 1.062, P < 0.001, FDR <0.001). Suggestive evidence showed that the Beta nerve growth factor increased the risk of MI (OR = 1.145, P = 0.025), but the stem cell factor (SCF) demonstrated a potential protective effect against MI (OR = 0.910, P = 0.04). SCF and hepatocyte growth factor (HGF) exhibited potential protective effects against SAP. No inflammatory cytokine was associated with UAP. Monocyte chemotactic protein-1 was linked to an increased risk of VHD (OR = 1.056, P = 0.049). Higher levels of interleukin-13 (IL-13), interferon gamma-induced protein 10 (IP-10), and growth-regulated oncogene-alpha were associated with increased susceptibility to HF. Elevated basic fibroblast growth factor (bFGF) levels exhibited protective effects against AA (OR = 0.751, P = 0.038). Reverse MR analyses revealed that AA significantly decreased circulating TNF-related apoptosis-inducing ligand (TRAIL) levels (OR = 0.907, P < 0.001, FDR = 0.01). MI significantly increased circulating IL-12-p70 levels (OR = 1.146, P < 0.001, FDR = 0.014). Suggestive evidence indicated the Causal effects of six CVDs on 17 circulating inflammatory cytokines. ConclusionsThis study clarified the causal relationships between specific inflammatory cytokines and six CVDs, providing novel insights and evidence into the genetic involvement of inflammatory cytokines in CVDs. These inflammatory cytokines may be potential biomarkers for early disease diagnosis and treatment evaluation.

Customized Vascular Repair Microenvironment: Poly(lactic acid)-Gelatin Nanofibrous Scaffold Decorated with bFGF and Ag@Fe3O4 Core-Shell Nanowires.

Vascular defects caused by trauma or vascular diseases can significantly impact normal blood circulation, resulting in serious health complications. Vascular grafts have evolved as a popular approach for vascular reconstruction with promising outcomes. However, four of the greatest challenges for successful application of small-diameter vascular grafts are (1) postoperative anti-infection, (2) preventing thrombosis formation, (3) utilizing the inflammatory response to the graft to induce tissue regeneration and repair, and (4) noninvasive monitoring of the scaffold and integration. The present study demonstrated a basic fibroblast growth factor (bFGF) and oleic acid dispersed Ag@Fe3O4 core-shell nanowires (OA-Ag@Fe3O4 CSNWs) codecorated poly(lactic acid) (PLA)/gelatin (Gel) multifunctional electrospun vascular grafts (bAPG). The Ag@Fe3O4 CSNWs have sustained Ag+ release and exceptional photothermal capabilities to effectively suppress bacterial infections both in vitro and in vivo, noninvasive magnetic resonance imaging (MRI) modality to monitor the position of the graft, and antiplatelet adhesion properties to promise long-term patency. The gradually released bFGF from the bAPG scaffold promotes the M2 macrophage polarization and enhances the recruitment of macrophages, endothelial cells (ECs) and fibroblast cells. This significant regulation of diverse cell behavior has been proven to be beneficial to vascular repair and regeneration both in vitro and in vivo. Therefore, this study supplies a method to prepare multifunctional vascular-repair materials and is expected to represent a significant guidance and reference to the development of biomaterials for vascular tissue engineering.

Enhanced fibrocartilage regeneration at the tendon-bone interface injury through extracellular matrix hydrogel laden with bFGF-overexpressing human urine-derived stem cells

The tendon-bone interface (TBI) is crucial in the transfer of mechanical loads; however, it is susceptible to injuries that frequently result in healing via fibrous scar tissue formation. Consequently, regeneration of the fibrocartilaginous zone has become a pivotal area subject. At present, the use of stem cells represents a notably promising approach for TBI treatment. Especially, human urine-derived stem cells (hUSCs) present a practical option for cell-based therapies. Nevertheless, the chondrogenic differentiation potential of hUSCs is limited. To address this, basic fibroblast growth factor (bFGF) was transinfected into hUSCs to bolster their differentiation capacity and facilitate the formation of fibrocartilage in the target area. Additionally, the local immune microenvironment dramatically influences TBI healing, with macrophages playing a vital role. Effective healing relies on the phenotype transition of macrophages, with an imbalance often leading to insufficient regeneration and scar tissue formation. Innovations in biomaterials have provided new avenues for TBI repair, such as the porcine small intestinal submucosa (SIS) hydrogel developed in our prior research. In addition to serving as a carrier for stem cell delivery, the hydrogel’s bioactive components support tissue repair and immune regulation. In the present study, SIS hydrogel loaded with hUSCs that overexpress bFGF was used for the treatment of TBI injury, which is expected to correct inflammatory response imbalances, and promote macrophage polarization towards healing phenotypes, creating a favorable immune microenvironment. The combined effects of bFGF and the optimized immune setting are anticipated to enhance hUSCs’ chondrogenic potential, aiding in the functional restoration of TBI injuries.

Biohybrids for Combined Therapies of Skin Wounds: Agglomerates of Mesenchymal Stem Cells with Gelatin Hydrogel Beads Delivering Phages and Basic Fibroblast Growth Factor.

There is great interest in developing effective therapies for the treatment of skin wounds accompanied by deep tissue losses and severe infections. We have attempted to prepare biohybrids formed of agglomerates of mesenchymal stem cells (MSCs) with gelatin hydrogel beads (GEL beads) delivering bacteriophages (phages) as antibacterial agents and/or basic fibroblast growth factor (bFGF) for faster and better healing, providing combined therapies for these types of skin wounds. The gelatin beads were produced through a two-step process using basic and/or acidic gelatins with different isoelectric points. Escherichia coli (E. coli) and its specific T4 phages were propagated. Phages and/or bFGF were loaded within the GELs and their release rates and modes were obtained. The phage release from the basic GEL beads was quite fast; in contrast, the bFGF release from the acidic GEL beads was sustained, as anticipated. MSCs were isolated from mouse adipose tissues and 2D-cultured. Agglomerates of these MSCs with GEL beads were formed and maturated in 3D cultures, and their time-dependent changes were followed. In these 3D culture experiments, it was observed that the agglomerates with GEL beads were very healthy and the MSCs formed tissue-like structures in 7 days, while the MSC agglomerates were not healthy and shrunk considerably as a result of cell death.

Promoting successful healing of artificial trachea by intratracheal administration of basic fibroblast growth factor†.

This study evaluated the effect of intratracheal administration of basic fibroblast growth factor (bFGF) on tracheal healing following implantation of a novel layered polyglycolic acid (PGA) material to replace a critical-size defect in rat trachea. A critical-size defect in the rat cervical trachea was covered with PGA. Distilled water (DW) or 3.125, 6.25, 12.5 or 25 µg bFGF was administered into the trachea for 2 weeks (n = 6 for each of 5 groups). Regenerated areas of cilia, ciliary beat frequency and ciliary transport function (CTF) in the centre of the PGA were measured. To examine potential side effects of intratracheal administration of bFGF, the right lower lobe was pathologically evaluated. All rats survived during the study period. Histological examination showed ciliated epithelization on the PGA material after 2 weeks. Bronchoscopy revealed stenosis due to granulation following administration of high concentrations of bFGF (12.5 and 25 µg). Compared with the DW group, groups administered 3.125, 6.25, 12.5 and 25 µg bFGF had significantly larger areas of regenerated cilia (15.2%, 27.0%, 41.3%, 33.1% and 31.0%, respectively; P = 0.00143), improved ciliary beat frequency (7.10, 8.18, 10.10, 9.50 and 9.50 Hz, respectively), and improved CTS (6.40, 9.54, 16.89, 16.41 and 14.29 µm/sec, respectively). Pathological examination of the right lower lobe revealed pulmonary fibrosis and hyperplasia with high concentrations of bFGF (12.5 and 25 µg). Intratracheal administration of bFGF effectively promoted tracheal regeneration at an optimal dose of 6.25 µg following implantation of an artificial trachea.

Safety and Efficacy of Multiple Escalating Doses of RC28-E for Neovascular Age-Related Macular Degeneration: A Phase 1b Trial.

To assess the safety and efficacy of repeated intravitreal injections of RC28-E, a novel bispecific antibody that simultaneously binds vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with neovascular age-related macular degeneration (AMD). This was a prospective, multicenter, open-label clinical trial; 37 patients with choroidal neovascularization secondary to AMD and best-corrected visual acuity (BCVA) letter scores between 73 and 34 were enrolled. Treatment regimens consisted of a 3-month loading phase and a pro re nata (PRN) maintenance phase. This study included three treatment groups: the 0.5, 1.0, and 2.0mg RC28-E groups, with escalating doses ranging from 0.5 to 2.0mg. Patients were evaluated monthly for 48weeks. Safety was assessed based on ocular and systemic adverse events (AEs), pharmacokinetic characteristics, and the presence of anti-RC28-E antibodies. Efficacy was assessed using the mean change in BCVA and central subfield thickness (CST) from baseline to week 48. Most AEs were mild or moderate. The most common AE was a minor injection-related subconjunctival hemorrhage (16.2%). The AEs did not increase with dose or repeated injections. At week 48, mean improvements in BCVA from baseline in the 0.5, 1.0, and 2.0mg groups were 6.1 ± 8.3, 9.9 ± 10.7, and 7.6 ± 9.38 letters, respectively; mean reductions in CST in the three groups were 112.1 ± 160.5, 175.1 ± 212.4, and 128.7 ± 145.8μm, respectively. The serum RC28-E concentrations in 95% of the patients were below the quantification limit of the assay. No significant change from baseline was observed in the mean plasma concentrations of VEGF or FGF over the 48weeks of treatment. Pre-treatment antibodies to RC28-E were detected in 1 of the 37 patients. Antibodies to RC28-E were detected in two patients after dosing with RC28-E for 48weeks. RC28-E was well tolerated and exhibited an overall favorable safety profile with evidence of improvements in BCVA and anatomical parameters.

Basic Fibroblast Growth Factor Accumulation in Culture Medium Masks the Direct Antitumor Effect of Anti-VEGF Agent Bevacizumab.

The direct antitumor effect of bevacizumab (BEV) has long been debated. Evidence of the direct antitumor activities of drugs are mainly obtained from in vitro experiments, which are greatly affected by experimental conditions. In this study, we evaluated the effect of BEV-containing medium renewal on the results of in vitro cytotoxicity experiments in A549 and U251 cancer cells. We observed starkly different results between the experiments with and without BEV-containing medium renewal. Specifically, BEV inhibited the tumor cell growth in the timely replacement with a BEV-containing medium but promoted tumor cell growth without medium renewal. Meanwhile, compared with the control, a significant basic fibroblast growth factor (bFGF) accumulation in the supernatant was observed in the group without medium renewal but none in that with replaced medium. Furthermore, bFGF neutralization partially reversed the pro-proliferative effect of BEV in the medium non-renewed group, while exogenous bFGF attenuated the tumor cell growth inhibition of BEV in the medium-renewed group. Our data explain the controversy over the direct antitumor effect of BEV in different studies from the perspective of the compensatory autocrine cytokines in tumor cells.

Tropism-shifted AAV-PHP.eB-mediated bFGF gene therapy promotes varied neurorestoration after ischemic stroke in mice.

AAV-PHP.eB is an artificial adeno-associated virus (AAV) that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically. While AAV-PHP.eB has been used in various disease models, its cellular tropism in cerebrovascular diseases remains unclear. In the present study, we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor (bFGF) gene therapy. Mice were injected intravenously with AAV-PHP.eB either 14 days prior to (pre-stroke) or 1 day following (post-stroke) transient middle cerebral artery occlusion. Notably, we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen (mNG). This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A (Ly6A). Furthermore, AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke. Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.

Preliminary investigation of endoscopic surgery for tympanic membrane perforation: Regenerative treatment compared with conventional surgery

PurposeTo compare surgical outcomes of regenerative treatment (RT) including basic fibroblast growth factor (bFGF) (Group-R) with the conventional method (Group-C) for patients with tympanic membrane perforation (TMP), both of whom underwent transcanal endoscopic ear surgery. MethodsThe study population of Group-R included 61 ears of 59 patients treated with RT-TMP in which TMP edges were disrupted mechanically and a gelatin sponge immersed in bFGF was inserted into the TMP. Fibrin glue was then dripped over the sponge. Group-C consisted of 13 patients who underwent conventional surgery before adopting the RT-TMP. Patients' characteristics and outcomes including TMP closure rates, and change in hearing level were evaluated three or more weeks after the surgery. ResultsThe baseline characteristics including size of TMP were not significantly different between the two groups. Although Group-R had significantly shorter operating time than Group-C, the complete TMP closure rates were 69 % (9/13) and 85 % (52/61), respectively. Air-conduction hearing thresholds showed significant improvements, and analysis of variance showed that Group-R achieved significant interactions other than at 8 kHz, implying better improvement in cases with TMP closure. The air-bone gaps also improved at all frequencies in both groups. Specifically, at 4 kHz, there was a trend showing better improvement in Group-R. ConclusionRT-TMP had a high TMP closure rate and good hearing improvement, with no significant differences compared with those of conventional surgery. This new therapy is simple and safe, and requires less operating time, and it could help improve the quality of life of patients with TMP.

Silk fibroin biohydrogel composites for loading and ordered release of multiple active ingredients with enhanced bioactivity

Bioactive hydrogels are currently receiving significant attention. In this study, silk fibroin tyramine-modified gelatin hydrogels (SF-TG) with varying degrees of tyramine root substitution were explored. The physicochemical property and biocompatibility of low degree of substitution tyramine-modified gelatin hydrogel (SF-LTG) and high degree of substitution tyramine-modified gelatin hydrogel (SF-HTG) were compared. The results showed that SF-LTG possessed better mechanical property and higher biocompatibility. Thus, SF-LTG was selected as a bioactive matrix and loaded with basic fibroblast growth factor (bFGF); subsequently, curcumin-coupled chitosan rods (CCCRs-EGF) enriched with epidermal growth factor (EGF) were added to obtain SF-LTG-bFGF@CCCRs-EGF hydrogels. The results showed that SF-LTG-bFGF@CCCRs-EGF retained the basic structural and mechanical properties of the SF-LTG matrix gel material and underwent multiple loading and orderly release with different activities while displaying antioxidant, anti-inflammatory, antimicrobial, and pro-cellular proliferation activities and orderly regulation of activity during wound healing. Therefore, the SF-LTG-bFGF@CCCRs-EGF hydrogel is of great value in healing complex wounds.

Recombinant collagen coating 3D printed PEGDA hydrogel tube loading with differentiable BMSCs to repair bile duct injury

Bile duct injury presents a significant clinical challenge following hepatobiliary surgery, necessitating advancements in the repair of damaged bile ducts is a persistent issue in biliary surgery. 3D printed tubular scaffolds have emerged as a promising approach for the repair of ductal tissues, yet the development of scaffolds that balance exceptional mechanical properties with biocompatibility remains an ongoing challenge. This study introduces a novel, bio-fabricated bilayer bile duct scaffold using a 3D printing technique. The scaffold comprises an inner layer of polyethylene glycol diacrylate (PEGDA) to provide high mechanical strength, and an outer layer of biocompatible, methacryloylated recombinant collagen type III (rColMA) loaded with basic fibroblast growth factor (bFGF)-encapsulated liposomes (bFGF@Lip). This design enables the controlled release of bFGF, creating an optimal environment for the growth and differentiation of bone marrow mesenchymal stem cells (BMSCs) into cholangiocyte-like cells. These cells are instrumental in the regeneration of bile duct tissues, evidenced by the pronounced expression of cholangiocyte differentiation markers CK19 and CFTR. The PEGDA//rColMA/bFGF@Lip bilayer bile duct scaffold can well simulate the bile duct structure, and the outer rColMA/bFGF@Lip hydrogel can well promote the growth and differentiation of BMSCs into bile duct epithelial cells. In vivo experiments showed that the scaffold did not cause cholestasis in the body. This new in vitro pre-differentiated active 3D printed scaffold provides new ideas for the study of bile duct tissue replacement.

Neohesperidin-loaded microemulsion for improved healing of Acinetobacter baumannii-infected wound

A wound is a complicated process that eventually induces marked tissue destruction, frequently complicated by a secondary bacterial infection. The chief goal of this investigation was to evaluate the plausible wound-healing action of neohesperidin. This was extended to explore the potential of microemulsion systems to boost its wound-healing activity. Two microemulsion systems of wheat germ oil were prepared and characterized. The nominated systems employed tween 80 as surfactant and capryol 90 as co-surfactant at weight ratios of 2:1 and 1:1. The cutaneous wound healing potential of the selected systems in the presence and absence of neohesperidin load were assessed in vivo employing experimentally induced wound model in rats. The induced dorsal skin wounds were additionally infected with Acinetobacter baumannii bacteria. The results reflected a promising wound healing potential of neohesperidin-loaded microemulsion systems and a significant reduction in the infected wound's bacterial count. The selected systems induced significant up-regulation of transforming growth factor (TGF-β), basic fibroblast growth factor (b-FGF), collagen-I, and cytokeratin-14 (K14), while metalloproteinase-1 (MMP-1), interleukin-6 (IL-6), and nuclear factor kabba B (NF-ĸB) levels were reduced. The wound-healing impact of neohesperidin could be confirmed via its angiogenesis, re-epithelization, collagen deposition, and antibacterial, and anti-inflammatory effects.

Gold nanoparticles coated with collagen-I and their wound healing activity in human skin fibroblast cells

The slow wound healing process has become a major health problem. Gold nanoparticles (AuNPs) have been used in various biomedical applications because of their unique properties. Type I collagen (Collagen-I) is a protein and be the most abundant type of collagen. This type of collagen can help the surrounding structure to maintain its rigidity. In this study, we stabilized the surface of AuNPs using Collagen-I (Collagen-I@AuNPs) and investigated the effect of Collagen-I@AuNPs on wound healing. The evaluation of inflammatory cytokine secretion, which were interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), was performed. We found that Collagen-I@AuNPs reduced the levels of IL-6 and TNF-α in scratched human skin fibroblast (HSF) cells. Furthermore, Collagen-I@AuNPs induced the expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), which are key growth factors involved in wound healing. This results in enhanced wound closure. In addition, Collagen-I@AuNPs were not toxic to HSF cells and facilitated the cellular uptake of particles inside HSF cells. Therefore, Collagen-I@AuNPs is a promising candidate for wound healing enhancement.