1.3D printed tissue engineering scaffolds combined with bone marrow mesenchymal stem cells transplantation to repair spinal cord injury
Jianhao WANG ; Yang LIU ; Xuanhao FU ; Peng YU ; Shiqing FENG
Chinese Journal of Orthopaedics 2021;41(6):376-385
Objective:Through histological analysis, immunofluorescence staining, electrophysiological detection and Sensory and motor function evaluation to investigate the effects of 3D printed hydrogel scaffold combined with bone marrow mesenchymal stem cells (BMSCs) in promoting functional recovery of spinal cord injury.Methods:10% GelMA hydrogel and 10 6 U stem cell suspension were prepared into bioink of appropriate concentration to construct the biomimetic spinal cord scaffold through 3D printing platform. The scaffold was placed in the medium and cultured in an environment of 37 ℃ CO 2 incubator. The microstructure of the scaffolds and the distribution of BMSC in the scaffolds was observed by scanning electron microscope. CAM/PI staining and confocal microscopy were used to observe the survival of stem cells in the scaffolds and determine the biocompatibility of the scaffolds. The scaffolds were implanted into the subcutaneous tissues of the back of rats, and the subcutaneous tissues were determined by HE staining to detect the immunogenicity of the scaffolds. After the rat model of hemicytoma defect was made, stents were transplanted for treatment, and confocal microscopy was used to evaluate the regeneration of neurons and axons in local area of spinal cord injury. At the same time, BBB score was used to evaluate motor function, mechanical pain score was used to evaluate sensory function, and surface electrode detection method was used to evaluate electrophysiological recovery weekly. Results:The long spindle shaped BSMC were uniformly distributed in the scaffold with a loose reticular structure. The scaffolds had good biocompatibility, and the cell survival rate of the prepared scaffolds reached 96% after 24 hours of printing. After 28 days of subcutaneous transplantation, the immune rejection was mild and immunogenicity was low. It was shown that the regenerated spinal cord tissue in the treatment group was significantly increased compared with the control group, which was widely distributed with cells after 28 days by HE staining. It was confirmed that part of the regenerated spinal cord tissue was neurons by immunohistochemical staining.Compared with the injured group, the regeneration of neurons and axons in the treatment group were significantly increased by immunofluorescence staining and confocal microscopy. In the treatment group, the BBB score recovered to 10 points, while the control group only recovered to about 1 point in the first week, which was statistically significant. And it recovered to 17 in the fourth week, while the control group only recovered to about 4 point in the four week, which was statistically significant. The Angle of inclined plate support of the treatment group was restored to 40 degrees, while it was only restored to 22 degrees in the control group. The pain threshold of the treatment group decreased to 18.5 points, which was not statistically different from that of the control group. The latent recovery effect of electrophysiology in the treatment group was the same as that in the sham operation group and better than that in the control group.Conclusion:3D printing hydrogel scaffold with loose network structure is suitable for cell proliferation. It has well biological survival, low cytotoxicity and low immunogenicity, which promoted neurons and axons to recovery and extend so as to effectively promote the recovery of motor function, sensory function and neural signal transmission rate after spinal cord injury.
2.Angiotensin-(1-7)/Mas receptor axis protects cardiomyocytes against high glucose-induced injury by modulating nuclear factor-κB pathway
Weijie LIANG ; Jingfu CHEN ; Mingcai SONG ; Liqiu MO ; Wanying PAN ; Jianhao LI ; Jianqiang FENG ; Wenzhu ZHANG
Chinese Journal of Pathophysiology 2015;(2):267-273
AIM:Tostudywhe ther theangiotens in-(1-7)[Ang-(1-7)]/Mas receptor axis protects cardio-myocytes against high glucose (HG)-induced injury by inhibiting nuclear factor-κB (NF-κB) pathway.METHODS:The cell viability was measured by CCK-8 assay.The intracellular levels of reactive oxygen species ( ROS) were detected by DCFH-DA staining .The number of apoptotic cells was tested by Hoechst 33258 nuclear staining .Mitochondrial membrane potential ( MMP) was examined by JC-1 staining.The levels of NF-κB p65 subunit and cleaved caspase-3 protein were de-termined by Western blotting.RESULTS: Treatment of H9c2 cardiac cells with 35 mmol/L glucose (HG) for 30, 60, 90, 120 and 150 min significantly enhanced the levels of phosphorated ( p) NF-κB p65, peaking at 60 min.Co-treatment of the cells with 1 μmol/L Ang-(1-7) and HG for 60 min attenuated the up-regulation of p-NF-κB p65 induced by HG. Co-treatment of the cells with Ang-(1-7) at concentrations of 0.1~30μmol/L and HG for 24 h inhibited HG-induced cy-totoxicity, evidenced by an increase in cell viability .On the other hand, 1 μmol/L Ang-(1-7) ameliorated HG-induced apoptosis, oxidative stress and mitochondrial damage , indicated by decreases in the number of apoptotic cells , cleaved caspase-3 level, ROS generation and MMP loss .However, the above cardioprotective effects of Ang-(1-7) were markedly blocked by A-779, an antagonist of Ang-(1-7) receptor (Mas receptor).Similarly, co-treatment of H9c2 cardiac cells with 100 μmol/L PDTC ( an inhibitor of NF-κB) and HG for 24 h also obviously reduced the above injuries induced by HG.CONCLUSION:Ang-(1-7)/Mas receptor axis prevents the cardiomyocytes from the HG-induced injury by inhibiting NF-κB pathway .
3.Clinical application of LARS artificial ligament in anterior cruciate ligament reconstruction: an update
Jianhao FENG ; Yihong XU ; Weidong XU
Chinese Journal of Trauma 2023;39(8):756-762
The anterior cruciate ligament (ACL) is one of the most crucial components to maintain knee joint stability and also the most vulnerable structure during knee-related sports activities. ACL injuries often cause knee instability, difficulty in returning to sports, and secondary degenerative knee disease. Although using autograft to reconstruct the ACL is currently a popular choice in clinical settings, it has drawbacks such as limited autograft source, donor site morbidity and delayed return to sports. Ligament advanced reinforcement system (LARS) artificial ligament possesses unique advantages such as wide availability, no donor-site morbidity, and early recovery, avoiding the problems associated with autograft reconstruction of ACL, and it has drawn increasing attention in recent years. In this paper, the authors reviewed the characteristics of LARS artificial ligament and its application in ACL reconstruction, so as to provide reference for clinical treatment of ACL injuries.
4.The interpretation of the American Academy of Orthopaedic Surgeons "management of anterior cruciate ligament injuries evidence-based clinical practice guideline (2022)"
Jianhao FENG ; Shiyi CHEN ; Yingfang AO ; Weidong XU
Chinese Journal of Orthopaedics 2023;43(3):205-212
The anterior cruciate ligament (ACL) injury is a common sports injury, which can lead to the knee unstable, make it difficult for the patient to return to sports, and cause post-traumatic osteoarthritis. The difficulty of its clinical diagnosis and treatment has always been the focus of sports medicine research. In August 2022, the American Association of Orthopaedic Surgeons updated and published "evidence-based clinical practice guideline on management of ACL injuries (2022 version)" based on the "evidence-based clinical practice guideline on management of ACL injuries (2014 version)". In the prevention, diagnosis and treatment of ACL injuries, the new guideline offers 8 recommendations and 7 options according to different evidence strength. To assist clinicians in the diagnosis and treatment of ACL injuries, this article provides an interpretation of the new guideline. In comparison to the 2014 version, the new guideline does not recommend allografts any more, shortens the time for reconstruction after ACL injury from 5 months to 3 months, adds advice that ACL reconstruction can be combined with anterolateral ligament reconstruction or lateral extra-articular tenodesis, and does not recommend ACL repair. The new guideline also shares many similarities with the domestic "clinical evidence-based guideline for the diagnosis and treatment of anterior cruciate ligament injury (2022 version)", both of which advocate history and physical examination at diagnosis, early reconstruction, the use of autologous bone-patellar tendon-bone or hamstring tendon, and either single-bundle or double-bundle ACL reconstruction. The new ACL guidelines of the American Association of Orthopaedic Surgeons lack specific recommendations on artificial ligaments, techniques for bone tunnel creation, and rehabilitation programs, all of which are of concern to domestic physicians because they are based on evidence-based research from abroad. Therefore, in order to improve the diagnosis and treatment of ACL injuries in China, clinicians should not only follow the new ACL guidelines of the American Association of Orthopaedic Surgeons, but also combine the characteristics of Chinese patients, clinical practice, and pertinent domestic guidelines when diagnosing and treating ACL injuries.
5.Advances in anterolateral ligament reconstruction: clinical practice and controversy
Jianhao FENG ; Yihong XU ; Weidong XU
Chinese Journal of Orthopaedics 2023;43(5):328-336
Rupture of the anterior cruciate ligament (ACL) is one of the most frequent forms of knee sports injuries. Nowadays, ACL reconstruction is commonly performed to help patients restore their rotational stability. However, in patients with high risk factors, the risk of ACL reconstruction failure remains high, primarily because of continuous postoperative anterolateral rotational instability. This rotational instability after ACL reconstruction has prompted researchers to focus on the anterolateral complex of the knee, such as iliotibial tract and anterolateral ligament (ALL). Among them, ALL has remained largely unappreciated for more than a century since its discovery in 1879. Even though it is still controversial, most studies in recent years have supported the anterolateral ligament as an independent ligament and a crucial anatomical component for preserving the rotational stability of the knee joint. Although augmentation of the anterolateral complex has experienced twists and turns, the anatomic ALL reconstruction, which can be performed minimally invasively and has a low risk of complications and minimal injury, is reappearing as a key strategy to address this problem. Currently, the majority of scholars believe that the need for combined ALL reconstruction during ACL reconstruction should be taken into account when there is severe rotational instability present, such as high-grade pivot shift test preoperatively, ACL revision surgery, and high requirements for rotational stability, such as age less than 25 years and the need to participate in pivoting sports. The corresponding suggested criteria are also put forth in the authoritative consensus of both domestic and foreign sources. However, the surgical indications chosen by different experts based on their individual experiences are not all consistent. Due to conflicting reports on the actual impact of ALL reconstruction on improving rotational stability and whether it will excessively restrict knee's internal rotation function, there is still much debate among researchers regarding whether ALL reconstruction and ACL reconstruction should be combined. Currently, there are two main reconstruction techniques: ALL single bundle reconstruction and Y-construct ALL double bundle reconstruction. Y-construct ALL double bundle reconstruction has a better ability to restore the original anatomy and is recommended in the consensus, but there is still a lack of randomized controlled trials between the two techniques. Therefore, the combination of ALL reconstruction at the time of ACL reconstruction has been clinically started in recent years for patients who are susceptible to failure after ACL reconstruction, which also raises many controversies.
6.All-inside anterior cruciate ligament reconstruction: a review of development, evolution and clinical significance
Jianhao FENG ; Yihong XU ; Weidong XU
Chinese Journal of Orthopaedics 2023;43(8):526-533
Rupture of anterior cruciate ligament (ACL) is one of the most common sports injuries of the knee, which may cause limitation of motor function and degeneration of the knee, seriously affecting patients' living quality. Currently, arthroscopic ACL reconstruction (ACLR) has been identified as the gold standard for ACL rupture. In an effort to further increase surgical accuracy and decrease surgical trauma so as to promotes quick recovery, all-inside ACLR has gained increasing attention in recent years. All-inside ACLR is as effective as traditional reconstruction, but it has benefits such as the preservation of tendons, preservation of bone mass, reduction of postoperative pain, prevention of synovial fluid leakage, expansion of the tendon-bone healing area, avoidance of complications related to extrusion screws, and suitability for children and adolescents. However, applying of numerous novel techniques for all-inside ACLR increases the learning curve, operating time, and cost. Besides, improper bone tunnel fabrication and graft fixation may lead to the widening of the bone tunnel, affecting the surgical effect. Therefore, in order to provide a theoretical foundation for further promoting the clinical application of this technique, this article reviews the development, evolution, and clinical outcomes of this technique as well as its advantages and disadvantages.
7.All-inside versus full-tibial tunnel techniques of anterior cruciate ligament reconstruction: a systematic review and meta-analysis
Jianhao FENG ; Yihong XU ; Weidong XU
Chinese Journal of Orthopaedics 2023;43(16):1104-1114
Objective:To compare the clinical efficacy of arthroscopic all-inside technique versus full-tibial tunnel technique for anterior cruciate ligament (ACL) reconstruction.Methods:Literature on all-inside versus full-tibial tunnel for ACL reconstruction was retrieved from databases including China National Knowledge Infrastructure (CNKI), Wanfang Data, Full-text Database of Chinese Medical Journals, PubMed, Web of Science, and Cochrane Library from their establishment to February 2023. Meta-analysis was performed on the included studies. Random effects model was used if heterogeneity was large, while fixed effects model was used if heterogeneity was small.Results:A total of 13 studies with 511 cases in the all-inside group and 465 cases in the full-tibial tunnel group were included in the meta-analysis, with a mean follow-up of 6-25.8 months. Meta-analysis showed that the graft diameter [ MD=0.42, 95% CI (0.11, 0.73), P=0.007] and International Knee Documentation Committee (IKDC) subjective score [ MD=1.11, 95% CI (0.36, 1.86), P=0.004] of the all-inside group was larger than full-tibial tunnel group, and the tibial tunnel widening of the all-inside group was less than full-tibial tunnel group [ MD=-1.70, 95% CI (-2.38, -1.01), P<0.001]. There were no significant differences in IKDC objective score [ OR=1.09, 95% CI (0.67, 1.78), P=0.730], Lysholm score [ MD=0.99, 95% CI (-0.08, 2.05), P=0.070], Tegner activity score [ MD=-0.01, 95% CI (-0.48, 0.45), P=0.950], bilateral knee anterior laxity difference [ MD=0.32, 95% CI (-0.22, 0.86), P=0.250], negative rate of pivot shift test [ OR=0.80, 95% CI (0.33, 1.91), P=0.610], graft re-rupture rate [ OR=0.76, 95% CI (0.34, 1.74), P=0.524] and return to sport rate [ OR=1.56, 95% CI (0.85, 2.86), P=0.150]. Conclusion:All-inside ACL reconstruction provides satisfactory efficacy. Compared with full-tibial tunnel technique, it has the advantages of larger graft diameter and less tibial tunnel widening, with no difference in joint function within 2 years postoperatively.
8.Progress on the causes and management of bone tunnel enlargement after anterior cruciate ligament reconstruction
Jianhao FENG ; Yihong XU ; Weidong XU
Chinese Journal of Orthopaedics 2023;43(18):1241-1247
Anterior cruciate ligament (ACL) injury is a common sports injury of the knee joint, which can lead to knee instability, dyskinesia and secondary traumatic osteoarthritis, which seriously affects the quality of life of patients. As it is difficult to self-heal after ACL injury, arthroscopic ACL reconstruction is commonly used as a clinical treatment to restore knee stability and motion function. However, more and more studies have found that bone tunnel enlargement is common after ACL reconstruction. A variety of biological (such as immunological rejection, local inflammation) and mechanical (such as offset bone tunnel positioning, improper graft fixation, and aggressive rehabilitation) factors are considered to be important causes of bone tunnel enlargement. It is still controversial whether the enlargement of bone tunnels affects clinical outcomes, but most researchers believe that the enlargement of bone tunnels is detrimental to the creation of bone tunnels and the fixation of grafts in revision surgery. Therefore, minimizing postoperative bone tunnel enlargement has positive clinical implications. The existing methods mainly include the selection of autografts, the use of independent bone tunnel positioning technology, modified bone tunnel drilling method, the use of remnant preservation technique and all-inside technique, the development of progressive individualized rehabilitation programs, and biological methods such as platelet-rich plasma and autogenous periosteum wrapping graft to enhance graft tendon-bone healing. This article reviews the causes and countermeasures of bone tunnel enlargement after ACL reconstruction to provide theoretical basis and help reduce or avoid bone tunnel enlargement after ACL reconstruction.
9.Preliminary study on the application of abdominal aortic balloon occlusion in the treatment of cesarean scar pregnancy
Jianhao ZHANG ; Hongjian DUAN ; Yanping ZHAO ; Yuhong HOU ; Xinwei HAN ; Na LIU ; Ke HU ; Zhipeng FENG ; Ruixia GUO
Chinese Journal of Obstetrics and Gynecology 2020;55(8):516-520
Objective:To explore the clinical value by analyzing the application of abdominal aortic balloon occlusion in the uterine curettage treatment for patients with cesarean scar pregnancy (CSP).Methods:Totally 42 CSP patients in the first Affiliated Hospital of Zhengzhou University were analyzed retrospectively, 21 cases in the observation group, placing the balloon catheter to the abdominal aorta under the renal artery under the digital substraction angiography(DSA), conducting curettage under hysteroscopy or uterine laparoscopy immediately, and making intermittent blockage in abdominal aorta blood flow during the surgery;21 patients in the control group, conducting uterine artery embolization (UAE) before operation, conducting curettage under hysteroscopy or uterine laparoscopy after 1-3 days. The fluoroscopy time under DSA, body surface radiation dose, intraoperative blood loss, operation time, incidence of postoperative adverse reactions, hospitalization time and follow-up menstruation were comparatively analyzed.Results:All patients operated and retained the uterus successfully. In the control group, all 21 patients had different degrees of fever, pain and other symptoms after UAE. In the observation group and control group, the fluoroscopy time and body surface radiation dose under DSA respectively were (7.4±1.4) s, (5.4±1.1) mGy and (1 142.8±315.5) s, (1 442.0±300.0) mGy (both P<0.01);the average amount of intraoperative blood loss were (22±15), (19±14) ml ( P>0.05), the time of uterine curettage were (37±20), (42±19) minutes ( P>0.05);hospitalization time were (5.0±0.9), (7.7±1.3) days ( P<0.01). The follow-up period was more than 3 months, no adverse reactions were observed in the observation group; 4 cases of menstrual reduction and 1 case of intrauterine adhesions were found in the control group. Conclusion:Abdominal aortic balloon occlusion and UAE could effectively reduce intraoperative bleeding in uterine curettage for patients with CSP; abdominal aortic balloon occlusion has significant reduction of the X-ray dose, shorter hospitalization time, and fewer adverse events comparing to UAE.
10.Research progress of knee meniscal repair techniques.
Jianhao FENG ; Yihong XU ; Weidong XU
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(7):885-894
OBJECTIVE:
To review the research progress of meniscus repair in recent years, in order to provide help for the clinical decision-making of meniscus injury treatment.
METHODS:
The domestic and foreign literature related to meniscal repair in recent years was extensively reviewed to summarize the reasons for the prevalence of meniscal repair, surgical indications, various repair methods and long-term effectiveness, the need to deal with mechanical structural abnormalities, biological enhancement repair technology, rehabilitation treatment, and so on.
RESULTS:
In order to delay the occurrence of osteoarthritis, the best treatment of meniscus has undergone an important change from partial meniscectomy to meniscal repair, and the indications for meniscal repair have been expanding. The mid- and long-term effectiveness of different meniscal repair methods are ideal. During meniscus repair, the abnormality of lower limb force line and meniscus protrusion should be corrected at the same time. There are controversies about the biological enhancement technology to promote meniscus healing and rehabilitation programs, which need further study.
CONCLUSION
Meniscal repair can restore the normal mechanical conduction of lower limbs and reduce the incidence of traumatic osteoarthritis, but the poor blood supply and healing ability of meniscal tissue bring difficulties to meniscal repair. Further development of new biological enhanced repair technology and individualized rehabilitation program and verification of its effectiveness will be an important research direction.
Humans
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Menisci, Tibial/surgery*
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Knee Joint/surgery*
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Meniscectomy/methods*
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Lower Extremity
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Osteoarthritis