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Neurocritical Care · 2021 ·Vol. 35 ·期 2 ·367-378 · IF 3.21

Is the CT Blend Sign Composed of Two Parts of Blood with Different Age?

Li Yinghui,Ren Siying,Wang Likun,Mao Yuanhong,Wu Guofeng,Li Qi,Tang Zhouping

Background Blend sign on initial computed tomography (CT) is associated with poor outcome in patients with intracerebral hemorrhage (ICH). However, the mechanisms underlying the blend sign formation are poorly understood. The present study aimed to explore the possible mechanism of the CT blend sign in patients with ICH. Methods Seventy healthy rabbits were selected to prepare an ICH model. The animals were assigned to a whole blood group + whole blood group (ww group, 50 rabbits), a whole blood + plasma group (wp group, 10 rabbits) or a whole blood + serum group (ws group, 10 rabbits). The animals of the ww group were allocated to five subgroups based on the interval between the first infusion of blood and the second one. The subgroups included ww 1 h group (with an interval of 1 h), ww 2 h group, ww 3 h group, ww 4 h group and ww 5 h group. The rabbits from each group received first infusion of 0.3 mL of whole blood into the basal ganglia area to form a hematoma. Then, they received a second infusion of the same amount of whole blood, plasma or serum into the brain to form another hematoma adjacent to the first one. Results A hematoma with two densities on brain CT could be formed in each group after a second infusion of blood into the brain. A significant difference in CT attenuation values was observed between the hyperattenuation and the hypoattenuation in all the groups. However, only the morphological features of the hematoma in the ww group was in accordance with the CT blend sign observed in humans. The CT attenuation values in the hypodensity area of the ww 4 h group or the ww 5 h group were decreased compared with the ww 1 h group to the ww 3 h group. Conclusions The CT blend sign observed in humans might be composed of two parts of blood with different ages. The hypodense area might be blood with older age and the hyperdense area might be new bleeding.

研究领域: 医学影像学 · 神经病学
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Scientific Reports · 2024 ·Vol. 14 ·期 1 ·1-9 · IF 3.8

Postmortem/dynamic distribution of ethanol and its nonoxidative metabolites in poisoned rabbits

Shi Qianwen,Wang Lele,Li Wenyue,Feng Yongming,Wei Zhiwen,Yun Keming

Nonoxidative ethanol metabolites have been reported as ethanol biomarkers in clinical and forensic cases. However, their forensic toxicokinetics are still unclear. The study aimed to simultaneously research the postmortem distribution and dynamic distribution of ethanol and its nonoxidative metabolites in 62 poisoned rabbits. Firstly, 32 rabbits were randomly divided into three groups and sacrificed after three doses ethanol, and their organs were collected to study the postmortem distribution of ethanol and its nonoxidative metabolites. The results showed that the distribution trends of ethanol and its nonoxidative metabolites were basically same between different groups, and ethanol could be better detected by collecting body fluids, while the nonoxidative metabolites could be better detected by collecting the heart, liver, kidney and testis. Secondly, 30 rabbits after 1/2LD 50 ethanol intragastric administration were sacrificed at 10 time points, and their organs were collected to study the dynamic distribution of ethanol and its nonoxidative metabolites. The results showed the concentrations of ethanol and its nonoxidative metabolites increased with time and then decreased. All analytes could be detected in all samples within 8 h, with the exception of ethyl oleate, which kept high level in muscle and vitreous humor, and could be detected within 4 h.

CAS / MDL: 64-18-6
研究领域: 法医学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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WORLD JOURNAL OF GASTROENTEROLOGY · 2019 · IF 3.411

Silicone-covered biodegradable magnesium stent for treating benign esophageal stricture in a rabbit model

Kai Yang,Jun Cao,Tian-Wen Yuan,Yue-Qi Zhu,Bi Zhou,Ying-Sheng Cheng

BACKGROUND Stent insertion can effective alleviate the symptoms of benign esophageal strictures (BES). Magnesium alloy stents are a good candidate because of biological safety, but show a poor corrosion resistance and a quick loss of mechanical support in vivo . AIM To test the therapeutic and adverse effects of a silicone-covered magnesium alloy biodegradable esophageal stent. METHODS Fifteen rabbits underwent silicone-covered biodegradable magnesium stent insertion into the benign esophageal stricture under fluoroscopic guidance (stent group). The wall reconstruction and tissue reaction of stenotic esophagus in the stent group were compared with those of six esophageal stricture models (control group). Esophagography was performed at 1, 2, and 3 weeks. Four, six, and five rabbits in the stent group and two rabbits in the control groups were euthanized, respectively, at each time point for histological examination. RESULTS All stent insertions were well tolerated. The esophageal diameters at immediately, 1, 2 and 3 wk were 9.8 ± 0.3 mm, 9.7 ± 0.7 mm, 9.4 ± 0.8 mm, and 9.2 ± 0.5 mm, respectively ( vs 4.9 ± 0.3 mm before stent insertion; P < 0.05). Magnesium stents migrated in eight rabbits [one at 1 wk (1/15), three at 2 wk (3/11), and four at 3 wk (4/5)]. Esophageal wall remodeling (thinner epithelial and smooth muscle layers) was found significantly thinner in the stent group than in the control group ( P < 0.05). Esophageal injury and collagen deposition following stent insertion were similar and did not differ compared to rabbits with esophageal stricture and normal rabbits ( P > 0.05). CONCLUSION Esophageal silicone-covered biodegradable magnesium stent insertion is feasible for BES without causing severe injury or tissue reaction. Our study suggests that insertion of silicone-covered magnesium esophageal stent is a promising approach for treating BES.

CAS / MDL: 111-65-9
研究领域: 医学 · 生物材料学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Scientific Reports · 2022 ·Vol. 12 ·期 1 ·1-12 · IF 4.996

Implementation of sodium alginate-Fe3O4 to localize undiagnosed small pulmonary nodules for surgical management in a preclinical rabbit model

Zhang Zhi-xuan,Lv Lu,Shi Ai-hua,Li Yun-hao,Wang Tian-ren,Guo Yuan-hang,Hu Bao-juan,Yan Xiao-peng,Fu Jun-ke,Ma Feng,Wang Hao-hua,Lv Yi,Zhang Yong

Many methods are used to locate preoperative small pulmonary nodules. However, deficiencies of complications and success rates exist. We introduce a novel magnetic gel for small pulmonary nodules localization in rabbit model, and furtherly evaluate its safety and feasibility. Rabbits were used as the experimental objects. A magnetic gel was used as a tracer magnet, mixed as sodium alginate-Fe 3 O 4 magnetic fluid and calcium gluconate solution. In short-term localization, a coaxial double-cavity puncture needle was applied to inject the gel into the lung after thoracotomy, and a pursuit magnet made of Nd-Fe-B permanent magnetic materials was used to attract the gel representing location of the nodule. In long-term localization, the gel was injected under X-ray guidance. Imaging changes to the lung were observed under X-ray daily. Thoracotomy was performed to excise tissue containing the gel, and hematoxylin–eosin staining was used to observe the tissue on postoperative days 1, 3, 5, and 7. Observe tissues morphology of heart, liver, spleen, and kidney in the same way. The gel was formed after injection and drew lung tissue to form a protrusion from the lung surface under the applied magnetic field. No complication was observed. The shape and position of the gel had not changed when viewed under X-ray. Pathological analysis showed the gel had a clear boundary without diffusion of magnetic fluid. All tissues retained good histologic morphology and no magnetic fluid was observed. Our study preliminarily suggested that the technique using sodium alginate-Fe 3 O 4 magnetic gel to locate small pulmonary nodules with guidance of X-ray, and to search for them under an applied magnetic field during the operation is safe and feasible.

CAS / MDL: 1317-61-9 9005-38-3
研究领域: 医学影像学 · 外科手术 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Biomaterialia · 2018 · IF 6.383

An electrospun fiber reinforced scaffold promotes total meniscus regeneration in rabbit meniscectomy model

Shuang Gao,Mingxue Chen,Pei Wang,Yan Li,Zhiguo Yuan,Weimin Guo,Zengzeng Zhang,Xueliang Zhang,Xiaoguang Jing,Xu Li,Shuyun Liu,Xiang Sui,Tingfei Xi,Quanyi Guo

Low vascularization in meniscus limits its regeneration ability after injury, and tissue engineering is the most promising method to achieve meniscus regeneration. In this study, we fabricated a kind of composite scaffold by decellularized meniscus extracellular matrix/polycaprolactone (DMECM/PCL) electrospinning fibers and porous DMECM, in which DMECM/PCL fibers were used as reinforcing component. The tensile modulus of the composite scaffold in longitudinal and crosswise directions were 8.5 ± 1.9 and 2.3 ± 0.3 MPa, respectively. Besides that, the DMECM/PCL electrospinning fibers enhanced suture resistance of the composite scaffold more than 5 times than DMECM scaffold effectively. In vitro cytocompatibility showed that the porous structure provided by DMECM component facilitated meniscus cells’ proliferation. DMECM was also the main component to regulate cell behaviors, which promoted meniscus cells expressing extracellular matrix related genes such as COL I, COL II, SOX9 and AGG . Rabbits with total meniscectomy were used as animal model to evaluated the composited scaffolds performance in vivo at 3 and 6 months. Results showed that rabbits with scaffold implanting could regenerate neo-menisci in both time points. The neo-menisci had similar histology structure and biochemical content with native menisci. Although neo-menisci had inferior tensile modulus than native ones, its modulus was improved with implanting time prolonging. MRI imaging showed the signal of neo-meniscus in the body is clear, and X-ray imaging of knee joints demonstrated the implantation of scaffolds could relief joint space narrowing. Moreover, rabbits with neo-menisci had better cartilage condition in femoral condyle and tibial plateau compared than meniscectomy group. Statement of Significance We fabricated the meniscus scaffold by combining porous decellularized meniscus extracellular matrix (DMECM) and DMECM/PCL electrospinning fibers together, which used the porous structure of DMECM, and the good tensile property of electrospinning fibers. We believe single material cannot satisfy increasing needs of scaffold. Therefore, we combined not only materials but also fabrication methods together to develop scaffold to make good use of each part. DMECM in electrospinning fibers also made these two components possible to be integrated through crosslinking. Compared to existing meniscus scaffold, the composite scaffold had (1) soft structure and extrusion would not happen after implantation, (2) ability to be trimmed to suitable shape during surgery, and (3) good resistance to suture.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 生物材料学 · 组织工程学 · 医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF PHARMACEUTICAL SCIENCES · 2023 · IF 3.8

Tacrolimus-Loaded Cationic Nanoemulsion In-Situ Gel System: In-Vitro Characterization and Performance in a Dry-Eye Rabbit Model

Qiuhe Wang,Zheng Wu,Feifei Wang,Hua Zhang,Li Gan

Dry eye disease (DED) is a highly prevalent ocular surface disease that affects life quality and reduces productivity at work. The purpose of this study is to improve the efficacy of tacrolimus (FK506) in the treatment of DED using the special eye surface retention properties of cationic nanoemulsion (CNE) modified by thermosensitive in-situ gel (ISG) (CNE-ISG). The precorneal retention of CNE-ISG containing 0.05% FK506 (50 min) was longer than that of CNE containing 0.05% FK506 (25 min) and commercial suspension containing 0.1% FK506 (Talymus®) (10 min). Successfully modeled dry-eye rabbits were treated with 0.05% CNE-ISG (twice/day), 0.05% CNE and 0.1% suspension (Talymus®) (thrice/day). Schirmer's tear secretion test showed no significant difference between the CNE-ISG group and the healthy group after 5 days of treatment ( p  > 0.05). The results of a tear ferning test (TFT) showed that the tear-fern-like crystal branches in the CNE-ISG group returned to normal after 5 days of treatment. Histological analysis showed that the number of goblet cells in the CNE-ISG group significantly increased. HET-CAM stimulation test showed that the CNE-ISG group had no ocular irritation. The above results indicated that CNE-ISG might be a promising delivery system and as an effective dosage form was employed for FK506 in the treatment of DED.

CAS / MDL: 56-81-5 25301-02-4
研究领域: 药剂学 · 眼科医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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American Journal of Translational Research · 2018 · IF 3.061

Diagnostic utility of fluorogenic peptide-conjugated Au nanoparticle probe corroborated by rabbit model of mild cartilage injury and panel of osteoarthritic patients

Zhenlong Liu,Xiaoqing Hu,Peng Yang,Jiying Zhang,Chunyan Zhou,Yingfang Ao

Using a rabbit model of early-stage osteoarthritis (OA) and a sampling patients with OA, we evaluated the diagnostic utility of a fluorogenic peptide-conjugated gold nanoparticle (AuNP) probe in detecting mild cartilage injury, based on the a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) enzyme. Synthesis of this fluorescent turn-on probe (or AU-probe) required conjugation of AuNPs with a fluorescein isothiocyanate (FITC)-modified ADAMTS-4-specific peptide (DVQEFRGVTAVIR). Synovial fluid samples were then collected from 48 adult rabbits and 100 patients for comparative testing (ADAMTS-4 ELISA and AU-probe). Rabbit and patient MRI images were also evaluated and scored. Receiver operating characteristic (ROC) curve analysis was applied to various diagnostic methods (MRI, ELISA, AU-probe, and arthroscopy), performing comparisons via logistic regression. In rabbits, the AU-probe proved nonsuperior to MRI T2 mapping and ELISA (fluorescence cutpoint > 864.965 au). In patient groups, logistic regression analysis indicated that combined AU-probe/MRI testing outperformed MRI alone, thus offsetting low MRI sensitivity and low AU-probe specificity for improved detection of mild cartilage injury (sensitivity, 82.5%; specificity, 80.0%). We have consequently confirmed the efficacy of this AU-probe, using ADAMTS-4 activity in synovial fluid to diagnose mild cartilage injury. Combining the AU-probe with conventional MRI assessment proved optimal in this setting.

CAS / MDL: 13453-07-1 16961-25-4
研究领域: 医学 · 生物技术 · 诊断学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Biomed Research International · 2019 · IF 2.197

Use of a Novel, Reinforced, Low Immunogenic, Porcine Small Intestine Submucosa Patch to Repair a Supraspinatus Tendon Defect in a Rabbit Model

Xuancheng Zhang,Zhaoyi Fang,Eunshinae Cho,Kai Huang,Jinzhong Zhao,Jia Jiang,Xiaoqiao Huangfu

Background. Repairs of large to massive rotator cuff tears have a high failure rate. We investigated the efficacy of a novel, reinforced, low immunogenic, porcine small intestine submucosa (SIS) patch to repair a supraspinatus tendon defect in a rabbit model. We hypothesized that the histological and biomechanical results of SIS patch repair would be comparable with those of autologous fascia lata (FL) repair. Methods. The study mainly comprised two parts. First, the characteristics of the SIS patch were evaluated, including its micromorphology, mechanical properties, and immunogenic properties. Second, a supraspinatus tendon defect model was created in 36 rabbits (72 shoulders). The bilateral shoulders were randomly chosen to undergo repair using either a SIS patch (SIS group) or autologous FL (FL group). At 4, 8, and 12 weeks, histological analysis was performed using four shoulders from each group, and biomechanical tests were performed using eight shoulders from each group. Results. The SIS patch was a three-dimensional construct mainly composed of collagen fibers. The mean single and double suture retention loads of the SIS patch were 48.6 ± 5.8 N and 117.9 ± 2.7 N, respectively. The DNA content in the SIS patch was 53.9 ± 10.9 ng/mg dry weight. Both the histological score and ultimate load to failure increased in a time-dependent manner in both groups, with no significant differences between the SIS and FL groups at 12 weeks. Conclusion. Repair of a large supraspinatus tendon defect using a reinforced, low immunogenic, SIS patch achieves similar effects as autologous FL in a rabbit model. This novel patch might be useful to be employed as a structural tissue replacement in medical activities.

CAS / MDL: 39450-01-6 9003-98-9
研究领域: 运动医学 · 组织工程 · 生物材料学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Omega · 2023 · IF 4.1

3D-Printed Composite Bioceramic Scaffolds for Bone and Cartilage Integrated Regeneration

Nanjian Xu,Dezhi Lu,Lei Qiang,Yihao Liu,Dalin Yin,Zhiyong Wang,Yongxiang Luo,Chen Yang,Zhenjiang Ma,Hui Ma,Jinwu Wang

Osteoarthritis may result in both cartilage and subchondral bone damage. It is a significant challenge to simultaneously repair cartilage due to the distinct biological properties between cartilage and bone. Here, strontium copper tetrasilicate/β-tricalcium phosphate (Wesselsite[SrCuSi4O10]/Ca3(PO4)2, WES-TCP) composite scaffolds with different WES contents (1, 2, and 4 wt %) were fabricated via a three-dimensional (3D) printing method for the osteochondral regeneration. The physicochemical properties and biological activities of the scaffolds were systematically investigated. 2WES-TCP (WES-TCP with 2 wt % WES) composite scaffolds not only improved the compressive strength but also enhanced the proliferation of both rabbit bone mesenchymal stem cells (rBMSCs) and chondrocytes, as well as their differentiation. The in vivo study further confirmed that WES-TCP scaffolds significantly promoted the regeneration of both bone and cartilage tissue in rabbit osteochondral defects compared with pure TCP scaffolds owing to the sustained and controlled release of bioactive ions (Si, Cu, and Sr) from bioactive scaffolds. These results show that 3D-printed WES-TCP scaffolds with bilineage bioactivities take full advantage of the bifunctional properties of bioceramics to reconstruct the complex osteochondral interface, which broadens the approach to engineering therapeutic platforms for biomedical applications.

研究领域: 组织工程学 · 再生医学 · 生物材料学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF BIOMATERIALS APPLICATIONS · 2025 · IF 2.5

Caprine dermal scaffolds for repair of full-thickness skin wounds in rabbits

Parvez Ahmad,Sangeeta Devi Khangembam,Anil Kumar Gangwar,Vipin Kumar Yadav,Prafull Kumar Singh,Yogendra Singh,Ravi Prakash Goyal,Surendra Pratap Chakraverty,Rajesh Kumar Verma

Biological scaffolds prepared after decellularization are used for the restoration of damaged tissues. A number of chemicals are used for bioscaffold preparation, and some of them damage their composition and architecture. Herein, we investigated the Sapindus mukorossi fruit pericarp extract (SPE) (5%) for decellularization of the caprine dermis. The dermal samples were processed in 5% SPE over magnetic stirrer for 96h at room temperature. The decellularization efficiency of SPE was analyzed by histological examination, DAPI staining, scanning electron microscopy (SEM), quantification of DNA hydroxyproline and hemocompatibility determination. Further, these acellular caprine dermal scaffolds were transplanted on full thickness skin wounds of group III New Zealand white rabbits. The wounds were left open in group I (Sham) and reconstructed by autograft in group II (n = 6 in each group). Continuous agitation of native caprine dermal tissues in 5% SPE for 96 hours leads to complete decellularization without affecting the extracellular matrix architecture. Microscopic observation of decellularized samples did not show any nuclei. DNA quantity was reduced (p < .05) in decellularized samples and scaffolds were found to be hemocompatible. Complete healing was observed on day 28 in groups II and III. No significant difference was noted in IgG in all the groups. Quantitative assessment of MDA showed a significant increase in groups I and II. Our results suggested that the 5% SPE solution effectively decellularized the native caprine dermis and the scaffolds were well tolerated by the animals.

研究领域: 组织工程 · 再生医学 · 生物材料学
✓ 已验证 DOI PubMed 高影响因子
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International Journal of Nanomedicine · 2022 · IF 7.033

Superhydrophilic PLGA-Graft-PVP/PC Nanofiber Membranes for the Prevention of Epidural Adhesion

Qingxin Fan,Hao Wu,Qingquan Kong

Background The frequent occurrence of failed back surgery syndrome (FBSS) seriously affects the quality of life of postoperative lumbar patients. Epidural adhesion is the major factor in FBSS.Purpose A safe and effective antiadhesion material is urgently needed.Methods A superhydrophilic PLGA-g-PVP/PC nanofiber membrane (NFm) was prepared by electrospinning. FTIR was performed to identify its successful synthesis. Scanning electron microscopy, thermogravimetric analysis, differential scanning calorimetry, and water contact angle measurement were performed. CCK-8 assays were performed in primary rabbit fibroblasts (PRFs) and RAW264.7 cells to explore the cytotoxicity of PLGA-g-PVP/PC NFm. Calcein-AM/PI staining was used to measure the adhesion status in PRFs. ELISA was performed to measure the concentrations of TNF-α and IL-10 in RAW264.7 cells. In addition, the anti-epidural adhesion efficacy of the PLGA-g-PVP/PC NFm was determined in a rabbit model of lumbar laminectomy.Results The PLGA-g-PVP/PC NFm exhibited ultrastrong hydrophilicity and an appropriate degradation rate. Based on the results of the CCK-8 assays, PLGA-g-PVP/PC NFm had no cytotoxicity to PRFs and RAW264.7 cells. Calcein-AM/PI staining showed that PLGA-g-PVP/PC NFm could inhibit PRF adhesion. ELISAs showed that PLGA-g-PVP/PC NFm could attenuate lipopolysaccharide-induced macrophage activation. In vivo experiments further confirmed the favorable anti-epidural adhesion effect of PLGA-g-PVP/PC NFm and the lack of a strong inflammatory response.Conclusion In this study, PLGA-g-PVP/PC NFm was developed successfully to provide a safe and effective physical barrier for preventing epidural adhesion. PLGA-g-PVP/PC NFm provides a promising strategy for preventing postoperative adhesion and has potential for clinical translation.

研究领域: 生物医学工程 · 材料科学 · 神经外科
✓ 已验证 DOI PubMed 高影响因子
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Journal of Orthopaedic Surgery and Research · 2024 ·Vol. 19 ·期 1 ·1-17 · IF 2.8

NGF-BMSC-SF/CS composites for repairing knee joint osteochondral defects in rabbits: evaluation of the repair effect and potential underlying mechanisms

Zhang Yong,Huang Wenliang,Xiao Hongli,Ruan Shiqiang,Deng Jiang

Background With the rapid growth of the ageing population, chronic diseases such as osteoarthritis have become one of the major diseases affecting the quality of life of elderly people. The main pathological manifestation of osteoarthritis is articular cartilage damage. Alleviating and repairing damaged cartilage has always been a challenge. The application of cartilage tissue engineering methods has shown promise for articular cartilage repair. Many studies have used cartilage tissue engineering methods to repair damaged cartilage and obtained good results, but these methods still cannot be used clinically. Therefore, this study aimed to investigate the effect of incorporating nerve growth factor (NGF) into a silk fibroin (SF)/chitosan (CS) scaffold containing bone marrow-derived mesenchymal stem cells (BMSCs) on the repair of articular cartilage defects in the knees of rabbits and to explore the possible underlying mechanism involved. Materials and methods Nerve growth factor-loaded sustained-release microspheres were prepared by a double emulsion solvent evaporation method. SF/CS scaffolds were prepared by vacuum drying and chemical crosslinking. BMSCs were isolated and cultured by density gradient centrifugation and adherent culture. NGF-SF/CS-BMSC composites were prepared and implanted into articular cartilage defects in the knees of rabbits. The repair of articular cartilage was assessed by gross observation, imaging and histological staining at different time points after surgery. The repair effect was evaluated by the International Cartilage Repair Society (ICRS) score and a modified Wakitani score. In vitro experiments were also performed to observe the effect of different concentrations of NGF on the proliferation and directional differentiation of BMSCs on the SF/CS scaffold. Results In the repair of cartilage defects in rabbit knees, NGF-SF/CS-BMSCs resulted in higher ICRS scores and lower modified Wakitani scores. The in vitro results showed that there was no significant correlation between the proliferation of BMSCs and the addition of different concentrations of NGF. Additionally, there was no significant difference in the protein and mRNA expression of COL2a1 and ACAN between the groups after the addition of different concentrations of NGF. Conclusion NGF-SF/CS-BMSCs improved the repair of articular cartilage defects in the knees of rabbits. This repair effect may be related to the early promotion of subchondral bone repair.

研究领域: 生物医学工程 · 骨科 · 组织工程 · 再生医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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