Rabbit Model Research Articles

Effect of Danhong Injection on Articular Cartilage Degeneration in Rabbits with Knee Osteoarthritis

The aim of this research was to investigate the effect of Danhong injection nanoparticle (DIN) plus warm acupuncture (WA) on articular cartilage degeneration in knee osteoarthritis (KOA) rabbits. First, the KOA model and DIN were made. After success, the rabbits were randomly grouped: according to the treatment methods: controls, DIN, WA, and DIN+WA groups, with 10 rabbits in each group. The controls did not receive any treatment, and the other groups received corresponding treatment intervention, respectively. Through treatment, articular cartilage samples were collected. The bone morphology, LequesneMG score, Mankin score were analyzed. The safranin-fast green, toluidine blue, Terminal Deoxynucleotidyl Transferase Mediated dUTP Nick End Labeling (TUNEL), and immunohistochemical staining were observed. The levels of apoptosis-related factors were determined. The results showed that the KOA rabbit model and DIN were successfully constructed. Compared with other groups, the LequesneMG and Mankin scores of DIN+WA group decreased markedly (P < 0.05). Safranin-fast green and toluidine blue staining showed that the number of chondrocytes in DIN+WA group was markedly increased, which was more as against other groups. TUNEL staining revealed that the number of apoptotic chondrocytes was markedly reduced, and the apoptotic index was markedly lower in DIN+WA group as against other three groups (P < 0.05). Compared with other groups, Bax and Caspase-3 were markedly decreased, and Bcl-2 was markedly raised in DIN+WA group (P < 0.05). According to the review, the combined application of DIN and WA can promote the growth of chondrocytes, inhibit the apoptosis of chondrocytes, and effectively improve the degeneration of knee articular cartilage, which has application value.

P07-04 Biomarkers of arsenical vesicant lewisite ocular exposure in an in vivo rabbit model and effective countermeasures by dexamethasone

P07-04 Biomarkers of arsenical vesicant lewisite ocular exposure in an in vivo rabbit model and effective countermeasures by dexamethasone

Quantitative assessment of chlorine gas inhalation injury based on endoscopic OCT and spectral encoded interferometric microscope imaging with deep learning.

Chlorine exposure can cause severe airway injuries. While the acute effects of chlorine inhalation are well-documented, the structural changes resulting from the post-acute, high-level chlorine exposure remain less understood. Airway sloughing is one of the standards for doctors to evaluate the lung function. Here, we report the application of a high-resolution swept-source optical coherence tomography system to investigate the progression of injury based on airway sloughing evaluation in a chlorine inhalation rabbit model. This system employs a 1.2mm diameter flexible fiberoptic endoscopic probe via an endotracheal tube to capture in vivo large airway anatomical changes before and as early as 30minafter acute chlorine exposure. We conducted an animal study using New Zealand white rabbits exposed to acute chlorine gas (800 ppm, 6min) during ventilation and monitored them using optical coherence tomography (OCT) for 6h. To measure the volume of airway sloughing induced by chlorine gas, we utilized deep learning for the segmentation task on OCT images. The results showed that the volume of chlorine induced epithelial sloughing on rabbit tracheal walls initially increased, peaked around 30min, and then decreased. Furthermore, we utilized a spectral encoded interferometric microscopy system to study ex vivo airway cilia beating dynamics based on Doppler shift, aiding in elucidating how chlorine gas affects cilia beating function. Cilia movability and beating frequency were decreased because of the epithelium damage. This quantitative approach has the potential to enhance the diagnosis and monitoring of injuries from toxic gas inhalation and to evaluate the efficacy of antidote treatments for these injuries.

Promotion and Mechanism of Acupotomy on Chondrocyte Autophagy in Knee Osteoarthritis Rabbits.

To explore the effect of acupotomy intervention on autophagy of chondrocytes in rabbits with knee osteoarthritis (KOA), and to determine the possible mechanisms of acupotomy to alleviate cartilage degeneration. The modified Videman method was used to construct a KOA rabbit model. After modeling, 40 rabbits were randomly divided into 4 groups by a random number table: control; KOA (model); KOA + acupotomy (acupotomy), and KOA + sham acupotomy (sham), 10 in each group. After a 3-week treatment course, the knee joint activity was determined by the modified Lequesne MG index. Hematoxylin-eosin staining staining was used to examine the morphological changes of chondrocytes. Autophagy of chondrocytes was observed by transmission electron microscopy. The surface morphology of cartilage tissue was observed by scanning electron microscope. The mRNA and protein levels of AMP kinase/mammalian target of rapamycin/Unc-51 (AMPK/mTOR/ULK1) signal pathway key proteins, autophagy-related factor Beclin-1 and microtubule-associated protein 1A/1B light chain 3 (LC3) in rabbit knee cartilage were assessed by real-time fluorescence quantitative polymerase chain reaction and Western blot, respectively. The modified Lequesne MG score of acupotomy group was significantly lower than that of model group (P<0.05). Pathological results showed that chondrocyte autophagy decreased and cartilage surface was rough in the model group, which recovered after acupotomy treatment. The mRNA expressions of AMPK, ULK1, Beclin-1 and the protein levels of p-AMPK, p-ULK1, Beclin-1, and LC3 II/LC3 I were decreased in the model group, while the mRNA and protein expressions of mTOR were increased (P<0.01). However, acupotomy treatment reversed these abnormal changes (P<0.05). Acupotomy could effectively up-regulate the expressions of AMPK, ULK1 and Beclin1, reduce the expression of mTOR, promote autophagy, and alleviate joint degeneration. Acupotomy is a promising complementary and alternative therapy for KOA.

Sympathetic structural and electrophysiological remodeling in a rabbit model of reperfused myocardial infarction.

Chondroitin sulfate proteoglycans (CSPGs) inhibit sympathetic reinnervation in rodent hearts post-myocardial infarction (MI), causing regional hypoinnervation that is associated with supersensitivity of β-adrenergic receptors and increased arrhythmia susceptibility. To investigate the role of CSPGs and hypoinnervation in the heart of larger mammals, we used a rabbit model of reperfused MI and tested electrophysiological responses to sympathetic nerve stimulation (SNS). Innervated hearts from MI and sham rabbits were optically mapped using voltage and Ca2+-sensitive dyes. SNS was performed with electrical stimulation of the spinal cord, and β-adrenergic responsiveness was tested using isoproterenol. Sympathetic nerve density and CSPG expression were evaluated using immunohistochemistry. CSPGs were robustly expressed in the infarct region of all MI hearts, and the presence of CSPGs was associated with reduced sympathetic nerve density in the infarct versus remote region. Action potential duration (APD) dispersion and tendency for induction of ventricular tachycardia/fibrillation (VT/VF) were increased with SNS in MI but not sham hearts. SNS decreased APD at 80% repolarization (APD80) in MI but not sham hearts, whereas isoproterenol decreased APD80 in both groups. Isoproterenol also shortened Ca2+ transient duration at 80% repolarization in both groups but to a greater extent in MI hearts. Our data suggest that sympathetic remodeling post-MI is similar between rodents and rabbits, with CSPGs associated with sympathetic hypoinnervation. Despite a reduction in sympathetic nerve density, the infarct region of MI hearts remained responsive to both physiological SNS and isoproterenol, potentially through preserved or elevated β-adrenergic responsiveness, which may underlie increased APD dispersion and tendency for VT/VF.NEW & NOTEWORTHY Here, we show that CSPGs are present in the infarcts of rabbit hearts with reperfused MI, where they are associated with reduced sympathetic nerve density. Despite hypoinnervation, sympathetic responsiveness is maintained or enhanced in MI rabbit hearts, which also demonstrate increased APD dispersion and tendency for arrhythmias following sympathetic modulation. Together, this study indicates that the mechanisms of sympathetic remodeling post-MI are similar between rodents and rabbits, with hypoinnervation likely associated with enhanced β-adrenergic sensitivity.

Spatial lipidomic profiles of atherosclerotic plaques: A mass spectrometry imaging study

Lipids contribute to atherosclerotic cardiovascular disease but their roles are not fully understood. Spatial lipid composition of atherosclerotic plaques was compared between species focusing on aortic plaques from New Zealand White rabbits and carotid plaques from humans (n = 3), using matrix-assisted laser desorption/ionization mass spectrometry imaging. Histologically discriminant lipids within plaque features (neointima and media in rabbits, and lipid-necrotic core and fibrous cap/tissue in humans) included sphingomyelins, phosphatidylcholines, and cholesteryl esters. There were 67 differential lipids between rabbit plaque features and 199 differential lipids in human, each with variable importance in projection score ≥1.0 and p < 0.05. The lipid profile of plaques in the rabbit model closely mimicked that of human plaques and two key pathways (impact value ≥ 0.1), sphingolipid and glycerophospholipid metabolism, were disrupted by atherosclerosis in both species. Thus, mass spectrometry imaging of spatial biomarkers offers valuable insights into atherosclerosis.

Omega-3 polyunsaturated fatty acids, especially DHA and EPA, remold gut microbiota to suppress inflammation in rabbits with atherosclerosis

Atherosclerosis (AS) caused by a high-fat diet becomes a critical cause of cardiovascular diseases, which has been regarded as an urgent public health problem. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have many beneficial effects on human health. However, in recent years, the critical role of gut microbiota in atherosclerosis has been gradually proposed, and the impact of omega-3 PUFAs on cardiovascular diseases via gut microbiota in rabbits remains unknown. Likewise, the role of omega-3 PUFAs in regulating endothelial lesions, visceral injury, and vascular inflammation caused by high-fat diet-induced trimethylamine-nitrogen oxide (TMAO) has not been reported. Here, we investigated the effects of omega-3 PUFAs administered orally on atherosclerosis via an atherosclerotic rabbit model induced by a high-fat diet. The results showed that omega-3 PUFAs obtained from deep-sea fish oil can alleviate high-fat diet-induced atherosclerosis by inhibiting the increase of plasma TMAO and the formation of liver foam cells, reducing inflammatory factors, fat deposition, and plasma lipid levels and suppressing organ damage. Furthermore, gut microbiota disrupted by a high-fat diet were remodeled in rabbits treated with omega-3 PUFAs. These results further confirm that omega-3 PUFAs are promising nutritional and medical health foods that can be supplemented daily to prevent cardiovascular diseases.

A chimeric anti-vascularization immunomodulator prevents high-risk corneal transplantation rejection via ex vivo gene therapy

Corneal blindness affects greater than 5 million individuals, with over 180,000 corneal transplantations (CTs) performed annually. Inhigh-risk CTs, almost all grafts are rejected within 10 years. Herein, adeno-associated virus (AAV) ex vivo gene therapy was investigated to establish immune tolerance in the corneal allograft to prevent high-risk CT rejection. Our previous work has demonstrated that HLA-G contributes to ocular immune privilege by inhibiting both immune cells and neovascularization; however, homodimerization is a rate-limiting step for optimal HLA-G function. Therefore, a chimeric protein termed single chain immunomodulator (sclM), was engineered to mimic the native activity of the secreted HLA-G dimer complex and eliminate the need for homodimerization. In a murine corneal burn model, AAV8-sclM significantly reduced corneal vascularization and fibrosis. Next, ex vivo AAV8-scIM gene delivery to corneal allografts was evaluated in a high-risk CT rejection rabbit model. All sclM treated corneas were well tolerated and transparent after 42 days while 83% of vehicle treated corneas were rejected. Histologically, AAV-scIM treated corneas were devoid of immune cell infiltration, vascularization, with minimal fibrosis at the host-graft interface. The data collectively demonstrate that sclM gene therapy prevents corneal neovascularization, reduces trauma-induced corneal fibrosis, and prevents allogeneic CT rejection in a high-risk large animal model.

Hyperbaric oxygen treatment promotes tendon-bone interface healing in a rabbit model of rotator cuff tears.

Due to the high-intensity pressure that the shoulder cuff endures, it is prone to traumas and tears. The main critical function of the shoulder cuff muscles is to effectively facilitate shoulder movement and securely maintain the humeral head in the precise center of the joint cavity to prevent superior migration during abduction processes. Shoulder cuff injuries typically involve the muscle-tendon-bone interface, but existing repair techniques do not always guarantee complete and secure healing, leading to retears. Hyperbaric oxygen therapy, as an auxiliary treatment, can significantly promote the muscle-tendon-bone healing process. To explore the impact of hyperbaric oxygen therapy on the bone-tendon interface healing process in a rabbit model specifically designed for shoulder cuff tears, an experiment was conducted on New Zealand white rabbits by performing a full-thickness tear of the supraspinatus tendon in the left shoulder, followed by 2 hours per day of 100% oxygen treatment at 2 absolute atmospheres for 5 days. The results indicate that hyperbaric oxygen therapy significantly enhances vascularization at the interface between the shoulder cuff and tendon-bone, promotes collagen fiber regeneration in the tendon, improves the tensile strength of the tendon-bone complex, and does not have a significant effect on biomechanical stability. This suggests that hyperbaric oxygen therapy has a significant positive impact on the histological and biomechanical healing of shoulder cuff tears in rabbits, expediting the healing process of the tendon-bone interface.

ST-Segment Alterations in the Electrocardiogram of Acute Pulmonary Thromboembolism: A Rabbit Model

In this study, we investigated the mechanism underlying electrocardiogram (ECG) alterations in a rabbit model of acute pulmonary thromboembolism (PTE). Twelve healthy adult New Zealand white rabbits were used, with eight in the experimental group (PTE group) and four in the control group. After developing the rabbit model of acute PTE, ECG and coronary angiography were performed. HE staining was conducted on the right and left ventricular tissues, and polymerase chain reaction (PCR) was used to determine brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-α), and Troponin I (TNI) mRNA expression in the myocardium. There were considerable changes in the ST segment of the ECG in the PTE group. Coronary angiography revealed the absence of spasm, stenosis, and occlusion. In the plasma of the PTE group, the levels of D-dimer, BNP, TNF-α, and TNI were significantly elevated, and these changes were statistically significant (P&lt;0.05). PCR analysis of ventricular myocardial tissue indicated significantly higher levels of BNP, TNF-α, and TNI mRNA in the PTE group than in the control group. These differences were statistically significant (P&lt;0.05). The ST-T variations on the ECG of rabbits with acute PTE correlate strongly with the temporary changes in right heart volume caused by acute PTE.

Enhancing long-segmental tracheal restoration: A self-repairing hydrogel loaded with chondrocytokines for sutureless anastomosis and cartilage regeneration

Artificial tracheal substitutes encounter significant challenges during long-segmental tracheal defects (LSTD) reconstruction, notably early postoperative anastomotic stenosis and tracheal chondromalacia. Mitigating early anastomotic stenosis by creating a compliant sutureless substitute is pivotal. Enhancing its chondrogenic capacity is equally critical for sustained healthy tracheal cartilage regeneration. This study proposes a self-healing hydrogel for sutureless tracheal anastomosis to mitigate anastomotic stenosis, enriched with kartogenin (KGN) and transforming growth factor-β1 (TGFβ1) to bolster chondrogenic properties. Initially, two precursor solutions were prepared: 1) aldehyde-modified hyaluronic acid with sulfonation and β-cyclodextrin-CHO loaded with KGN; 2) hydrazide-grafted gelatin loaded with TGFβ1. Coextrusion of these solutions resulted in a gelated G + TGFβ1/sH-CD + KGN hydrogel, characterized by a robust covalent bonding network of acylhydrazones between hydrazide and aldehyde groups, imparting excellent self-healing properties. The G + TGFβ1/sH-CD + KGN hydrogels, showcasing favorable cytocompatibility, excellent injectability, and rapid gelation, were loaded with bone marrow stem cells. These were customized into O-shaped rings and assembled into a malleable tracheal substitute using our established ring-to-tube method. This resultant compliant substitute facilitated sutureless anastomosis of LSTD in a rabbit model, attributed to the Schiff base reaction between the hydrogel's carbonyl group and the tissue's amino group. Notably, the tracheal substitute reduced early postoperative anastomotic stenosis, maintained tracheal patency, alleviated sputum blockage, promoted reepithelization, and increased the survival rate of the experimental rabbits. The sustained release of chondrocytokines resulted in excellent tracheal cartilage regeneration. Employing chondrocytokines-loaded hydrogels with self-healing properties represents a significant advancement in sutureless tracheal anastomosis and tracheal cartilage regeneration, holding promising potential in inhibiting early postoperative anastomotic stenosis and tracheal chondromalacia when treating LSTD.

Evaluation of bi-layer silk fibroin grafts for onlay urethroplasty in a rabbit model of urethral stricture disease.

Background: Autologous tissues such as buccal mucosa (BM) are widely used for reconstruction of urethral strictures; however, limitations such as donor site morbidity and scarce tissue supply require the development of alternative biomaterials for urethral repair. The goals of this study were to determine the safety and efficacy of bi-layer silk fibroin (BLSF) matrices for urethral stricture repair and compare histological and functional outcomes to the standard approach, BM urethroplasty under good laboratory practices.Material and methods: A total of 13 rabbits exhibiting urethral stricture formation following electrocoagulation injury were treated with onlay urethroplasty with either acellular BLSF (N=7) or autologous BM (N=6) grafts for 3months. Uninjured control rabbits were maintained in parallel (N=4).Results and conclusion: Animals receiving BLSF implants were demonstrated to be functionally equivalent to BM grafts in their ability to restored strictured calibers, support micturition and promote tissue regeneration with minimal inflammation.

Mucosal Injection of the Silicon Phthalocyanine Pc 4 in a Rabbit Model-A Pilot Study.

The silicon phthalocyanine Pc 4 is a photosensitizing agent previously shown to be a promising treatment for cutaneous neoplasms using photodynamic therapy (PDT). Based on prior preclinical studies, we believe Pc 4-PDT has potential as a targeted treatment of human recurrent respiratory papillomatosis or laryngeal leukoplakia by direct injection into mucosal surfaces. This was a proof-of-concept pilot study assessing direct mucosal injection of Pc 4 into buccal and vocal fold mucosae in a rabbit model. Five New Zealand white rabbits underwent tattooing of bilateral buccal mucosae to delineate injection sites, followed by submucosal injections of control and Pc 4 solutions. Rabbits were monitored for post-injection tolerance. Punch biopsies were obtained from injected mucosa and assessed histopathologically. Once the buccal mucosa was found to be tolerant, vocal folds of three rabbits were injected. The rabbits were then sacrificed, and laryngeal tissue was assessed histopathologically. All rabbits tolerated injection of Pc 4 and control solutions into buccal mucosa with no evidence of gross visual inflammatory changes and no changes in behavior or masticatory function. Histopathologic analysis of Pc 4 injected buccal and control mucosal tissue revealed mild focal histological changes and no stigmata of diffuse inflammatory reactions. The histopathologic analysis of Pc 4 injected into laryngeal tissue revealed similar findings with addition of mild eosinophilia in one sample. Direct mucosal injection of Pc 4 in rabbit buccal and vocal fold mucosae appears to be well tolerated with no gross inflammatory changes, and only mild histopathologic inflammatory changes observed. NA Laryngoscope, 2024.

Interleukin-4-Loaded Gelatin Methacryloyl Hydrogel Promotes Subcutaneous Chondrogenesis of Engineered Auricular Cartilage in a Rabbit Model.

Tissue engineering technology offers a promising solution for ear reconstruction; however, it faces the challenge of foreign body reaction and neocartilage malformation. This study investigates the impact of interleukin-4 (IL-4), an anti-inflammatory factor, on cartilage regeneration of hydrogel encapsulating autologous auricular chondrocytes in a rabbit subcutaneous environment. Initially, we assessed the influence of IL-4 on chondrocyte proliferation and determined the appropriate concentration using the CCK-8 test in vitro. Subsequently, we loaded IL-4 into gelatin methacryloyl (GelMA) hydrogel containing chondrocytes and measured its release profile through ELISA. The constructs were then implanted autologously into rabbits' subcutis, and after 3, 7, 14, and 28 days, cartilage matrix formation was evaluated by histological examinations, and gene expression levels were detected by qRT-PCR. Results demonstrated that IL-4 promotes chondrocyte proliferation in vitro, and maximum release from constructs occurred during the first week. In the rabbit subcutaneous implantation model, IL-4-loaded constructs (20 ng/mL) maintained a superior chondrocytic phenotype compared to controls with increased expression of anti-inflammatory factors. These findings highlight IL-4 as a potential strategy for promoting chondrogenesis in a subcutaneous environment and improving ear reconstruction.

Physiologically based pharmacokinetic models for systemic disposition of protein therapeutics in rabbits.

Physiologically based pharmacokinetic (PBPK) modelling is an important tool to predict drug disposition in the body. Rabbits play a pivotal role as a highly valued small animal model, particularly in the field of ocular therapeutics, where they serve as a crucial link between preclinical research and clinical applications. In this context, we have developed PBPK models designed specifically for rabbits, with a focus on accurately predicting the pharmacokinetic profiles of protein therapeutics following intravenous administration. Our goal was to comprehend the influence of key physiological factors on systemic disposition of antibodies and their functional derivatives. For the development of the systemic PBPK models, rabbit physiological factors such as gene expression, body weight, neonatal fragment crystallizable receptor (FcRn) binding, target binding, target concentrations, and target turnover rate were meticulously considered. Additionally, key protein parameters, encompassing hydrodynamic radius, binding kinetic constants (KD, koff), internal degradation of the protein-target complex, and renal clearance, were represented in the models. Our final rabbit models demonstrated a robust correlation between predicted and observed serum concentration-time profiles after single intravenous administration in rabbits, covering IgG, Fab, F(ab)2, Fc, and Fc fusion proteins from various publications. These pharmacokinetic simulations offer a promising platform for translating preclinical findings to clinical settings. The presented rabbit intravenous PBPK models lay an important foundation for more specific applications of protein therapeutics in ocular drug development.

Visualization of Brain Tumors with Infrared-Labeled Aptamers for Fluorescence-Guided Surgery.

Gliomas remain challenging brain tumors to treat due to their infiltrative nature. Accurately identifying tumor boundaries during surgery is crucial for successful resection. This study introduces an innovative intraoperative visualization method utilizing surgical fluorescence microscopy to precisely locate tumor cell dissemination. Here, the focus is on the development of a novel contrasting agent (IR-Glint) for intraoperative visualization of human glial tumors comprising infrared-labeled Glint aptamers. The specificity of IR-Glint is assessed using flow cytometry and microscopy on primary cell cultures. In vivo effectiveness is studied on mouse and rabbit models, employing orthotopic xenotransplantation of human brain gliomas with various imaging techniques, including PET/CT, in vivo fluorescence visualization, confocal laser scanning, and surgical microscopy. The experiments validate the potential of IR-Glint for the intraoperative visualization of gliomas using infrared imaging. IR-Glint penetrates the blood-brain barrier and can be used for both intravenous and surface applications, allowing clear visualization of the tumor. The surface application directly to the brain reduces the dosage required and mitigates potential toxic effects on the patient. The research shows the potential of infrared dye-labeled aptamers for accurately visualizing glial tumors during brain surgery. This novel aptamer-assisted fluorescence-guided surgery (AptaFGS) may pave the way for future advancements in the field of neurosurgery.

Antibiotic-eluting scaffolds with responsive dual-release kinetics facilitate bone healing and eliminate S. aureus infection

Osteomyelitis (OM) is a progressive, inflammatory infection of bone caused predominately by Staphylococcus aureus. Herein, we engineered an antibiotic-eluting collagen-hydroxyapatite scaffold capable of eliminating infection and facilitating bone healing. An iterative freeze-drying and chemical crosslinking approach was leveraged to modify antibiotic release kinetics, resulting in a layered dual-release system whereby an initial rapid release of antibiotic to clear infection was followed by a sustained controlled release to prevent reoccurrence of infection. We observed that the presence of microbial collagenase accelerated antibiotic release from the crosslinked layer of the scaffold, indicating that the material is responsive to microbial activity. As exemplar drugs, vancomycin and gentamicin-eluting scaffolds were demonstrated to be bactericidal, and supported osteogenesis in vitro. In a pilot murine model of OM, vancomycin-eluting scaffolds were observed to reduce S. aureus infection within the tibia. Finally, in a rabbit model of chronic OM, gentamicin-eluting scaffolds both facilitated radial bone defect healing and eliminated S. aureus infection. These results show that antibiotic-eluting collagen-hydroxyapatite scaffolds are a one-stage therapy for OM, which when implanted into infected bone defects simultaneously eradicate infection and facilitate bone tissue healing.

BMP2 Diminishes Angiotensin II-Induced Atrial Fibrillation by Inhibiting NLRP3 Inflammasome Signaling in Atrial Fibroblasts.

Atrial fibrillation (AF) is the most common sustained arrhythmia to affect 1% of the global population and increases with age. Atrial fibrosis is a crucial substrate for promoting structural remodeling to cause atrial arrhythmogenesis. Bone morphogenic protein 2 (BMP2) has been reported to be involved in cardiac fibrogenesis. However, its role in modulating atrial fibrosis to affect AF development remains unknown. Our study aimed to investigate the expression of BMP2 under different AF conditions and the effect of BMP2 on the progression of atrial fibrosis using an angiotensin II (Ang II) rat model and an ex vivo cardiac fibroblast model. The qRT-PCR and Western blot assay showed increased BMP2 mRNA and protein levels in the atria of chronic AF patients and the right atria of a tachypacing rabbit model. In contrast, the levels of BMP2 receptor mRNA were comparable. The AF incidence of the Ang II rat was higher than that of a control rat, which was reduced by BMP2 treatment. Masson staining demonstrated an anti-fibrogenic impact on BMP2-subjected rat atria compared to only Ang II-treated rat atria. RNA-sequencing indicated the potential function of blocking NLRP3-associted inflammasome activation in BMP2-treated rat atrial tissues. In vitro, transfecting BMP2 shRNA into neonatal rat atrial fibroblasts upregulated the mRNA levels of NLRP3/Caspase-1/p20/ASC and the secretion of IL-1β and IL-6. In contrast, recombinant BMP2 protein attenuated the increased levels of the NLRP3 inflammasome pathway induced by Ang II. In summary, BMP2 opposes atrial fibrosis to alleviate AF susceptibility by inhibiting the activation of the inflammasome in atrial fibroblasts.

Injectable and self-healing sulfated hyaluronic acid/gelatin hydrogel as dual drug delivery system for circumferential tracheal repair

Stem cell-based therapies show promise for clinically addressing circumferential tracheal defects (CTD) through tissue engineering. However, creating a tissue-engineered tracheal tube possesses a healthy cartilage matrix and intact tube structure remains a challenge. A solution lies in the use of an injectable hydrogel with shape adaptability and chondrogenic capacity, serving as a practical and dependable platform for tubular tracheal cartilage regeneration. In this study, we developed an injectable hydrogel using modified natural polymers-hydrazide-grafted gelatin (Gelatin-ADH) and aldehyde-modified hyaluronic acid with sulfated groups (HA-CHO-SO3) via Schiff Base interaction. Additionally, aldehyde-modified β-cyclodextrin (β-CD-CHO) was introduced into the network during hydrogel formation. The negative sulfated groups and hydrophobic cavities of β-cyclodextrin facilitated the efficient encapsulation and sustained release of transforming growth factor-β1 (TGF-β1) and kartogenin (KGN) within our hydrogel. This synergistically promoted the chondrogenesis of loaded bone marrow stem cells (BMSCs). Subsequently, we employed this TGF-β1, KGN, and BMSCs loaded hydrogel to form a cartilage ring. This ring was then assembled into an engineered tracheal cartilage tube using our previously reported ring-to-tube strategy. Our results demonstrated that the engineered tracheal cartilage tube effectively repaired CTD in a rabbit model. Hence, this study introduces a novel hydrogel with significant clinical application potential for tracheal tissue engineering.

Correction: Regeneration of dental pulp via collagen hydrogel composited with resveratrol-loaded chitosan nanoparticle in a rabbit model of dental pulp injury

Correction: Regeneration of dental pulp via collagen hydrogel composited with resveratrol-loaded chitosan nanoparticle in a rabbit model of dental pulp injury