1.Repairing articular cartilage defects in rabbits using bone marrow stromal cell-derived chondrocytes compounded with poly(lactic-co-glycolic acid)
Yuming CUI ; Ji WU ; Yunyu HU
Chinese Journal of Tissue Engineering Research 2009;13(51):10049-10054
BACKGROUND: Matrix material for cartilage tissue engineering exhibits too fast or too slow chondrocytes degradation in vivo, affecting tissue regeneration and shaping reconstruction, which has troubled scholars.OBJECTIVE: To amply bone marrow stromal cells (BMSCs) and induce them to chondrocytes in vitro, so as to study the feasibility of repairing articular cartilage defects in rabbits using poly(lactic-co-glycolic acid) (PLGA) loaded with BMSC-derived chondrocytes.DESIGN, TIME AND SETTING: Comparative experiment was performed at the Institute of Orthopaedics in the Fourth Military Medical University of Chinese PLA and the Center Laboratory of the Airforce General Hospital of Chinese PLA between June 2002 and June 2008.MATERIALS: A total of 36 two-month-old New Zealand white rabbits were used, and 4-6 mL bone marrow was aspirated from bilateral femoral trochanters in each animal. Primary culture and subcultures were done. In subcultures, the medium contained bone morphogenetic protein-2 (100 μg/L.), and high polymer hyaluronic acid was spread on bottom of the culture flasks in advance.In this way, the BMSCs were induced into chondrocytes and the third passage of cells at the adjusted density of 2.0×10~(10)/L wereco-cultured with PLGA for 24 hours, then PLGA-cell composites were prepared.METHODS: A defect of 4-mm in diameter and reaching medullary cavity were created in femoral condyles of 36 rabbits, and 36 right knees were treated with PLGA-cell composites, serving as experimental group, while 18 left knees with PLGA only as material group, and the other 18 knees remained untreated, as blank control group.MAIN OUTCOME MEASURES: At 4,8,12, 24 weeks after operation, the animals were euthanized and the newly formed tissues were observed macroscopically and microscopically, graded histologically, and analyzed statistically.RESULTS: Material group and blank control group shared identical outcomes of gross and histological observation, thus assigning into a control group. In the experimental group at 24 weeks, the defects were filled with white translucent cartilage tissue which appeared smooth and tenacious. The color and the luster were similar to that of normal cartilage, and was ill-demarcated from the surrounding normal cartilage. The cells on the surface paralleled to joint surface. Though the cells in the deep layer arranged disorderly, they tended to align vertically. The matrix was extensively stained. The subchondral bone formed.The tide mark basically recovered, and the new cartilage integrated with normal cartilage finely. In the control group, chondrocytes proliferated in the border, but in the bottom, there were mainly fibrous tissues. The histological grade of 12 and 24 weeks was different significantly from that of 4 and 8 weeks (P < 0.01). There were also significant differences between experimental group and control group at each time intervals after operation (P < 0.01).CONCLUSION: BMSCs were successfully induced into chondroncytes by use of bone morphogenetic protein-2 and high polymer hyaluronic acid. PLGA can be degraded and absorbed gradually while new cartilage tissues form. It can be used as a suitable scaffold material for repairing articular cartilage defects in tissue engineering.
2.Comparison of two osteoarthritis models in rabbit
Ruifu YANG ; Yunyu HU ; Yinsong WU
Orthopedic Journal of China 2006;0(19):-
[Objective]To establish osteoarthritis model in rabbit knees by two kinds of surgery methods,and to explore their applicable conditions.[Method]Seventeen rabbits were divided into three groups(Hulth group,ligament-excised group and control group),they were anesthetized and operated differently according to their group.The rabbits were sacrificed at 1,3 and 6 weeks after surgery.The femoral condylars were harvested and studied in both gross morphological and pathohistological aspect.[Result]The degeneration of articular cartilage of the two surgery groups got worse by time,and their Mankin's scores were significantly higher than those in the control group(P
3.Bridge tendon graft in no man's land: an experimental study in chickens.
Yaoping WU ; Yunyu HU ; Shubo CUI
Chinese Journal of Traumatology 2000;3(1):34-38
OBJECTIVE: To investigate the morphological characteristics of the bridge tendon grafting in no man's land to reconstruct the tendon defect and the effect of passive mobilization on it. METHODS: A 2 cm defect was made in bilateral flexor digitorum profundus tendons of the middle chicken toes, and was then transplanted to the opposite site to serve as a segmental autograft tendon. Postoperatively, passive mobilization of the left and right middle toes began at 5 and 21 d separately. Specimens were studied by light, scanning and transmission electron microscopy at 5, 10, 21 and 35 d. RESULTS: Early repair of the tendon-graft of the left middle toes was made by proliferation and ingrowth of the epitenon cells intermingled with newly-formed collagen fibers. A gliding surface formed at 10 and 21 d. The tendon graft itself played an active role in the repair. In contrast, adhesions obliterated the surface and occupied the space between the tendon graft and surrounding tissues in the right middle toes. CONCLUSIONS: It indicates that the use of the segmental bridge tendon graft in no man's land coupled with early passive motion stimulates an intrisic repair process in both the tendon stump and the autogenous tendon graft and results in a functional healing.
4.Multiple factor analysis of lumbar spine bone mass and densities in adolescents with early ankylosing spondylitis
Xing MA ; Yunyu HU ; Ping MA ; Quanping WANG ; Xiaojuan LI ; Rong LU ; Jun WANG ; Xinzhi XU ; Xiaoming WU
Chinese Journal of Tissue Engineering Research 2003;7(20):2825-2826
Aim To investigate the possible roles of age, bodyheight, mass and body mass index(BMI) in Lumbar1-4 bone mineralcontent (L1-4BMC), L1-4 areal bone mineral density(L1-44BMD) and L1-4volumetric bone mineral apparent density(L1-4BMAD) of Chinese adoles-cents with early ankylosing spondylitis (AS). Methods Thirty-one maleChinese adolescent outpatients with early AS were included. Age (y),total body mass (kg), height(cn) and body mass index (BMI, kg/m2)of subjects were obtained. L1-44BMC(g) and L1-4 BMD(g/cm2) were e-valuated by using DEXA, and L1-4 BMAD(L1-44BMC/Area3/2, g/cm3)was subsequently calculated. Correlation and multiple regression analyseswere performed. Results Multiple regression revealed that height ( P =0.000) and BMI(P=0.009) were significantly positively related toL1-44BMC (R=0.759, Radj2=0.545, P=0.000 <0.01), and heightplayed the pivotal roles in significant correlation with L144BMC(R =0. 676 Radj2 = 0. 439, P = 0. 000) . Body mass significantly positivelycorrelated with both L-44BMD ( R = 0. 657, Radj2 = 0. 412, P = 0. 000)and L1-4BMAD (R=0.551, Radj2=0.280, P=0.001) .Therefore,height as well as BMI significantly positively correlated with L144BMC andmass was definitely associated with both L1-4BMD and L1-4BMAD in ado-lescents with early AS in this study. Conclusion Height and mass couldhave significantly positive effects on axial bone mass and densities ofadolescents with early AS.
5.Surface modification of biodegradable polymer/TCP scaffolds and related research.
Xing MA ; Yunyu HU ; Xiaoming WU ; Yongnian YAN ; Zhuo XIONG ; Rong LU ; Jun WANG ; Dan LI ; Xinzhi XU
Journal of Biomedical Engineering 2008;25(3):571-577
Under laboratory condition, the compound materials of Poly (DL-lactic-co-glycolic acid)/Tricalcium phosphate [PLGA/TCP(L), with component ratio of 7:3] were fabricated by combining the thermally induced phase separation (TIPS) with solvent-casting particulate-leaching (SCPL) approach. On the other hand, rapid prototyping (RP) technique manufactured PLGA/TCP scaffolds [PLGA/TCP(RP)] were obtained. These two kinds of carriers were coated with collagen type I (Col I). The extracted bovine bone morphogenetic protein (bBMP) was loaded into carriers to establish biomimetic synthetic bones. PLGA/TCP(L) scaffolds, demineralized bone matrices (DBM) of bovine cancellous bone, PLGA/TCP(L) scaffolds, biomimetic synthetic bones and OsteoSet bone graft substitutes were investigated. Scanning electron microscopy revealed that the microarchitecture of PLGA/TCP(RP) scaffolds was much better than that of PLGA/TCP(L) scaffolds. The diameter of macropore of PLGA/TCP(RP) scaffold was 350 microm. The porosities of PLGA/ TCP(L) scaffolds, DBM, PLGA/TCP(RP) scaffolds and OsteoSet bone graft substitutes were 21.5%, 70.4%, 58.6% and 0%, respectively (P<0.01). Modification of PLGA/TCP scaffolds with collagen type I [PLGA/TCP(L)-Col I and PLGA/TCP(RP)-Col I] essentially increased the affinity of the carriers to bBMP. Among these synthetic materials, PLGA/TCP(RP)-Col I-bBMP composite is promising as a novel bone graft substitute due to its advanced fabrication technique, good tri-dimensional microarchitecture and ideal components.
Biocompatible Materials
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chemistry
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Bone Morphogenetic Proteins
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chemistry
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Bone Substitutes
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chemistry
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Calcium Phosphates
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chemistry
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Humans
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Lactic Acid
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chemistry
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Microscopy, Electron, Scanning
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Polyglycolic Acid
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chemistry
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Porosity
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Surface Properties
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Tissue Engineering
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methods
6.Therapeutic effect of microperimetry combined with optical coherence tomo-graphy angiography on large-diameter idiopathic macular hole after internal limiting membrane covering surgery
Lingyao WU ; Zhipeng YOU ; Yunyu TAN ; Xiaohan SU
Recent Advances in Ophthalmology 2024;44(9):707-713
Objective To explore the efficacy and safety of pars plan vitrectomy(PPV)combined with internal limit-ing membrane(ILM)covering surgery in patients with large-diameter idiopathic macular holes(IMH)using optical coher-ence tomography angiography(OCTA)and microperimetry.Methods Twenty-three eyes of 23 patients with large-diame-ter IMH treated at the Eye Hospital Affiliated with Nanchang University from February 2023 to July 2023 were selected.The patients'best-corrected visual acuity(BCVA),hole closure rate,microcirculation[perfusion density at the superficial cap-illary plexus(PSCP)and vascular density at the retinal superficial capillary plexus(VSCP)]in the macular area(divided into central,inner and outer regions),macular sensitivity(MS),fixation stability,and foveal avascular zone(FAZ)area were observed before surgery and at 1 week,1 month,3 months,and 6 months after surgery.Changes in eye parameters before and after surgery were compared,and the correlation between parameters was analyzed.Results After a 6-month follow-up,all macular holes in the affected eyes were closed,with a closure rate of 100%.Compared to before surgery,the BCVA of the patients improved gradually at 1 week,1 month,3 months,and 6 months after surgery,and the differ-ences between any two time points were statistically significant(all P<0.05).The FAZ area decreased at 1 week,1 month,3 months,and 6 months after surgery compared to before surgery,and the differences were statistically significant(all P<0.05).The VSCP in the three regions showed a decrease at 1 week postoperatively and an increase at 6 months postoperatively compared to before surgery,and the differences were statistically significant(both P<0.05).The PSCP in-creased at 3 months and 6 months postoperatively compared to before surgery,with statistically significant differences(both P<0.05).The 12° MS increased at 1 month,3 months,and 6 months after surgery compared to before surgery,with statistically significant differences(all P<0.05).The proportions of fixation points within 2° and 4° increased at 1 month,3 months,and 6 months postoperatively compared to before surgery,with statistically significant differences(all P<0.05).The proportion of fixation points within 4° increased at 1 week postoperatively compared to before surgery,with a statistically significant difference(P<0.05).Correlation analysis showed that preoperative MS and the proportion of fixa-tion points within 2° were negatively correlated with BCVA(logMAR)at 6 months postoperatively(r=-0.819,-0.790,both P<0.05),while preoperative FAZ area and minimum hole diameter were positively correlated with BCVA(logMAR)at 6 months postoperatively(r=0.596,0.853,both P<0.05).The preoperative VSCP in the inner and outer regions were negatively correlated with BCVA(logMAR)at 6 months postoperatively(r=-0.521,-0.570,both P<0.05).Conclu-sion The results of OCTA and microperimetry show that after treatment with PPV and ILM covering surgery,the closure rate of large-diameter IMH is good,and all indicators have improved compared to before surgery.
8.Mechanism of joint injection of Caulophyllum robustum Maxim in the treatment of rheumatoid arthritis
Shaowa LYU ; Yunyu WU ; Quanli LIU ; Yuhan REN ; Yuyan GUO ; Haixue KUANG
China Pharmacy 2025;36(8):926-931
OBJECTIVE To explore the mechanism of joint injection of Caulophyllum robustum Maxim in the treatment of rheumatoid arthritis (RA). METHODS The targets of main saponins in C. robustum Maxim were obtained from Swiss Target Prediction, and the RA treatment targets collected from the GeneCards and OMIM database were intercrossed to establish an interaction network based on network pharmacology. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. RA model was established by injecting complete Freund’s adjuvant into the back of rabbits for verification. The arthritis index score, knee diameter and pain threshold of rabbits were compared. Pathological examination of rabbit synovial tissue was carried out. The levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and IL-6 in rabbit serum and synovial fluid were detected. The phosphorylation levels of tyrosine protein Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) proteins in rabbit synovium were detected. RESULTS Network pharmacology identified 143 intersection targets between the drug and RA. After the construction of the “drug-component-target” network, the core components of the network were echinocystic acid, oleanolic acid, hederagenin, cauloside A and cauloside C, etc. Additionally, the top 10 core targets of PPI network were SRC, STAT3, MAPK1, EGFR, PIK3CA, MAPK3, GRB2, JUN, PTPN11 and JAK2. The results of KEGG pathway analysis showed that the JAK/STAT signaling pathway was mainly involved in the treatment of RA by joint injection of C. robustum Maxim. Results of validation test showed that compared with model group, joint injection of C. robustum Maxim could reduce the swelling of rabbit knee joint, relieve the hyperplasia of synovial layer, reduce the hyperplasia of lower connective tissue, and reduce the number of inflammatory cells and capillaries. The arthritis index score (excluding low-dose group of C. robustum Maxim), knee diameter, the levels of TNF-α, IL-1β and IL-6 in serum and synovial fluid, and the protein phosphorylation levels of JAK2 and STAT3 were decreased significantly (P<0.05 of P<0.01), while the pain threshold were reduced significantly (P<0.01). CONCLUSIONS The core components that may alleviate the inflammatory response of RA in joint injection of C. robustum Maxim could include echinocystic acid, oleanolic acid, hederagenin, cauloside A, and cauloside C. Its mechanism may be related to the inhibition of JAK/STAT signaling pathway and the reduction of inflammatory responses.