Advancing drug delivery to articular cartilage: From single to multiple strategies

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

Discussion on internal fixation of Hoffa fractures / 中国骨伤

Hoffa fracture is an unstable intra-articular fracture with significant redisplacement tendency. It is easy to be missed diagnosis when accompanied by distal intercondylar or supracondylar fracture of femur. CT scan is the gold standard for the diagnosis of Hoffa fracture. The treatment principles are anatomic reduction of the articular surface, reliable internal fixation, and early functional activity. At present, the main treatment is arthroscopic screw fixation. During screw fixation, the tail cap of screw should be buried, resulting in non-healing iatrogenic injury of articular cartilage. In the early postoperative functional activity of knee joint, fracture block was repeatedly subjected to backward and upward shear force under the action of the tibial plateau, which is the main reason for the failure of internal fixation. Plate assisted screw fixation could increase local mechanical stability, but it still cannot avoid the defects of iatrogenic cartilage injury. At the same time, plate molding is required during the operation due to the absence of special anatomical plates, resulting in increased surgical trauma and time-consuming surgery. The ideal fixation method for Hoffa fracture should include:(1) Avoid iatrogenic injury of articular surface cartilage. (2) With the rear anti-shear barrier plate function.(3) The internal fixator is closer to the load interface, so as to obtain greater load and better fixed strength.

Analysis of influence of MR signs on Harris score in ARCO stages 2-4 femoral head necrosis / 中国骨伤

OBJECTIVE@#To analysis and determine MR signs of Harris score ARCO stages 2-4 in osteonecrosis of femoral head (ONFH).@*METHODS@#Thirty-four patients with ONFH of ARCO stages 2 to 4 who underwent routine MR, T2 mapping, 3D-SPACE sequence examination and Harris score were retrospectively collected from January 2019 to June 2020, and 3 patients were excluded, and 31 patients were finally included, including 23 males and 8 females, aged from 18 to 62 years old with an average of(40.0±10.8) years old. Among them 21 patients with bilateral femoral head necrosis, totally 52 cases, including 17 with ARCO stage 2 patients, 24 ARCO stage 3, and 11 ARCO stage 4. MR imaging signs (femoral head collapse depth, ONFH index, bone marrow edema, hyperplasia, grade and T2 value of cartilage injury, and joint effusion) were scored and measured on the picture archiving and communication system (PACS) workstation, and the cartilage quantitative parameter T2 value was calculated and measured on Siemens postprocessing workstation. Pearson correlation analysis was used to evaluate the correlation between various MR signs and Harris score, and then multiple linear regression analysis was used to examine impact of MR signs on Harris hip score.@*RESULTS@#Femoral head collapse depth(r=-0.563, P=0.000), grade of cartilage injury(r=-0.500, P=0.000), and joint effusion (r=-0.535, P=0.000) were negatively correlated with Harris score by Pearson correlation analysis. Multiple linear regression analysis showed that joint effusion(β=-6.198, P=0.001) and femoral head collapse depth(β=-4.085, P=0.014) had a significant negative impact on Harris hip score.@*CONCLUSION@#Femoral head collapse depth and joint effusion both had significant negative relationship with Harris hip score. It is recommended to routinely evaluate femoral head collapse depth and joint effusion quantitatively and gradedly, so as to efficiently and accurately assist clinical diagnosis and treatment.

Design and validation of a novel knee biomechanical test method / 生物医学工程学杂志

A novel structural dynamics test method and device were designed to test the biomechanical effects of dynamic axial loading on knee cartilage and meniscus. Firstly, the maximum acceleration signal-to-noise ratio of the experimental device was calculated by applying axial dynamic load to the experimental device under unloaded condition with different force hammers. Then the experimental samples were divided into non-specimen group (no specimen loaded), sham specimen group (loaded with polypropylene samples) and bovine knee joint specimen group (loaded with bovine knee joint samples) for testing. The test results show that the experimental device and method can provide stable axial dynamic load, and the experimental results have good repeatability. The final results confirm that the dynamic characteristics of experimental samples can be distinguished effectively by this device. The experimental method proposed in this study provides a new way to further study the biomechanical mechanism of knee joint structural response under axial dynamic load.

Advances in arthroscopic microfracture technique for repairing articular cartilage injuries / 国际外科学杂志

Articular cartilage injury is common in orthopedics. Improper exercises and physical trauma can lead to the injury of cartilage. Since articular cartilage lacks blood supply, once damaged, it is difficult for the cartilage to repair itself. If not treated effectively, cartilage injuries will develop into severe osteoarthritis affecting the whole joint. Arthroscopic microfracture technique can achieve better therapeutic effects than regular joint debridement, with simple procedures, minimal invasion, and low cost. However, the microfracture technique is limited by the patients′ age (under 45 years old) and the size of the cartilage defect area (less than 4 cm 2) Additionally, postoperative patients need to conduct strict and long-term rehabilitation trainings. Generally speaking, the short-term prognosis of microfracture is satisfactory. However, the repair tissue is mainly composed of fibrocartilage, which is inferior to hyaline cartilage because of its poor mechanical properties and anti-wear abilities. Therefore, the long-term effect is controversial. To conclude, arthroscopic microfracture is a recommended method for young patients with small cartilage defect areas, but its exact long-term clinical effects still need to be verified by further research. This paper reviews the operation protocol, clinical efficacy, and the mechanism of arthroscopic microfracture surgery, and aims to provides theoretical basis for its application in clinical treatment.

Study on the repair effect of lyophilized platelet lysate products on articular cartilage injury model of rat / 中国输血杂志

【Objective】 To discuss the repair effect of lyophilized platelet lysate (PL) products on articular cartilage injury model of rats. 【Methods】 A total of 25 SD rats were injected with typeⅡcollagenase at the right knuckle articular cavity respectively on day 1, 3 and 5 of experiment, and the modeling conditions were observed 14 days after the last injection of collagenase. The SD rats with successful modeling were randomly divided into three groups, and were injected with lyophilized PL [Group A, 1 mL/(mouse·time)], PL [Group B, 1 mL/(mouse·time)], and normal saline[Group C, 1 mL/(mouse·time)]. The above three substances were injected with corresponding drugs on day 0, 7, 14 and 21 of experiment based on the grouping conditions, and the changes of knee joint diameters of the rats from the three groups were observed and compared. On day 14 and 28, one rat in each group was randomly killed and two knuckle articular cavities of each were taken for tissue sampling, using hematoxylin-eosin staining (HE) and immunohistochemistry. 【Results】 After 14 days of modeling by injection of type Ⅱ collagenase, the proportion of successful modeling in rats was 84% (21/25), with the knee joint diameter (mm) before and after modeling at 12.84±1.14 vs 14.11±1.17(P<0.01). On day 14, 21 and 28, groups A and B were superior to group C in the knee joint diameter and activity improvement (P<0.05), with 13.33±1.16 vs 13.37±1.08 vs 14.21±1.08, 13.10±1.09 vs 13.01±1.04 vs 14.09±1.09 and 12.38±1.08 vs 12.51±1.03 vs 14.01±1.07, respectively. Histological observation showed that group A and B were superior to group C in the production and arrangement of chondrocytes and the positive expression of type Ⅱ collagen, and there was no significant difference between group A and group B. 【Conclusion】 The lyophilized PL has similar therapeutic effect to PL in the treatment and repair of articular cartilage injury, and is worthy of clinical application.

Efecto de las lesiones condrales asintomáticas en la recuperación del paciente laboral tras una lesión traumática de rodilla / Effect of asymptomatic chodral on the recovery of the working patient after a traumatic injury of the knee

Resumen: El objetivo principal del estudio fue analizar la asociación entre la presencia de lesiones cartilaginosas asintomáticas en pacientes con lesiones traumáticas de rodilla y su tiempo de baja y gasto mutual. Los objetivos secundarios fueron describir la prevalencia y epidemiología de estas lesiones y analizar si se asocian con la presencia de obesidad y un peor resultado final. Material y métodos: Revisión retrospectiva de una cohorte de todos los pacientes a los que se les realizó una artroscopía de rodilla tras una lesión traumática en un centro mutual en el año 2018. Se recogieron datos demográficos, diagnóstico, patología condral concomitante, tratamiento, clínica al alta, tiempo total de baja y el gasto derivado de ésta. Resultados: Fueron analizados 123 pacientes con una media de edad de 47 años, no se encontraron diferencias entre sexos ni respecto a la obesidad entre los grupos con y sin lesión condral. Las lesiones cartilaginosas fueron diagnosticadas en más de un tercio de los pacientes valorados (35.25%), la mayoría entre 48 y 53 años. La presencia de patología condral no fue un condicionante que aumentara los días de baja o el gasto total (p > 0.05). En pacientes con meniscectomía, la lesión condral aumenta el tiempo de baja (p = 0.03). Los tratamientos enfocados en la lesión condral no produjeron diferencias en cuanto a la duración de la baja ni en el gasto. Conclusión: El manejo de una lesión condral concomitante a nivel de la rodilla sigue presentando controversia. Podría implicar un factor de mal pronóstico de recuperación en pacientes con meniscopatía y las terapias actuales no han mostrado un beneficio claro en estos pacientes del entorno laboral.

Abstract: The objective of this study was to investigate the prevalence and epidemiology of knee cartilage lesions in the work environment, and to assess whether they increase the patient's work leave and thus also cost. We also analyzed the prevalence of concomitant pathology and how it affected recovery and final outcome. Material and methods: Monocentric retrospective cohort of patients with occupational injuries who underwent knee arthroscopy during 2018. Demographic data, diagnosis, concomitant chondral pathology, treatment, symptoms and signs at discharge, work leave and total cost were collected. Results: 123 patients were analyzed, with a mean age of 47 years. No differences were found between sexes or with respect to obesity. Asymptomatic chondral lesions were found in 35.25% of the patients, primarily the older ones (48-53 years). The presence of cartilaginous pathology did not increase days of work leave or total cost (p > 0.05). In patients with meniscopathy in whom meniscectomy is performed, the chondral lesion increased the number of days of work leave (p = 0.03). There were no differences in the number of days of work leave nor total cost for different treatments of chondral pathology. Conclusion: The management of a concomitant chondral knee lesion is still controversial. These lesions might convey poorer functional prognosis in patients with meniscopathy. Current therapies have not shown a clear benefit in work injuries.

Clinical characteristics of radial head fracture combined with capitulum cartilage injury / 中华创伤骨科杂志

Objective:To characterize the radial head fracture combined with capitulum cartilage injury (CCI).Methods:The data of 110 patients were analyzed retrospectively who had been treated for radial head fracture at Department of Orthopaedics, The Ninth People's Hospital of Wuxi from January 2011 to May 2020. They were 62 males and 48 females, aged from 17 to 74 years (average, 44.10 years). According to the finding of intraoperative exploration whether CCI was complicated or not, they were assigned into a CCI group and a CCI-free group. The diagnosis, location, size, type, operation method and postoperative recovery of CCI were observed in CCI group. The 2 groups were compared in terms of preoperative general data, range of forearm motion before and after operation and functional recovery of the limb by Mayo elbow performance score (MEPS).Results:CCI was complicated in 25 cases (type Ⅰ in 7 ones, type Ⅱ in 12 ones and type Ⅲ in 6 ones), involving all Mason types of radial head fracture, and located at the lateral capitellum in 13 cases, at the posterolateral capitellum in 9 cases and at the anterolateral capitellum in 3 cases. CCI was diagnosed before operation in 13 cases by physical examination after local anesthesia and imaging examination with a rate of 48% (12/25) for missed diagnosis. The preoperative flexion and extension (61.8°±13.7°) and rotation (60.0°±24.2°) in CCI group were significantly less than those in CCI-free group (77.7°±23.0° and 79.9°±21.9°) ( P<0.05); the Mason types of radial head fracture in CCI group were significantly more serious than those in CCI-free group ( P<0.05). There was no significant difference between the 2 groups in age, gender, combined injury, treatment of radial head fracture, follow-up time, range of forearm motion at the last follow-up or MEPS score ( P>0.05). Conclusions:CCI was complicated in 22.73%(25/110) of the radial head fractures in this cohort and found in all Mason types of radial head fracture, and mostly located at the lateral and posterolateral capitellum. CCI is likely to be missed by imaging examination. In patients with mild radial head fracture and suspected CCI, positive physical examination after local anesthesia is valuable for diagnosis of CCI complication and operative indication. Care should be taken to detect CCI complication by intraoperative exploration in surgery of radial head fracture.

Role and application of bone morphogenetic proteins in articular cartilage regeneration / 中国组织工程研究

BACKGROUND: Articular cartilage degeneration is the main cause of osteoarthritis. Bone morphogenetic proteins play an important role in cartilage regeneration and repair. OBJECTIVE: To review the research progress of bone morphogenetic protein in the process of articular cartilage regeneration. METHODS: A computer-based online search of PubMed and Elsevier databases was performed using the keywords “bone morphogenetic proteins, BMPs, arthritis, osteoarthritis, OA, cartilage, chondrocyte” in English. A total of 272 papers were retrieved, 96 of which were included in final analysis. Another 27 papers related to concepts were also included. Therefore, 123 papers are finally included. RESULTS AND CONCLUSION: Bone morphogenetic proteins participate in many biological processes including cell proliferation, differentiation, migration, and apoptosis, and play an important role in the formation of bone and cartilage. Bone morphogenetic proteins participate in a variety of signaling pathway cascades by binding to different receptors, which can protect articular cartilage from cartilage destruction caused by inflammation and trauma. Bone morphogenetic proteins alone or in combination with other cytokines can repair cartilage defects improve degenerative lesions, and promote the differentiation and regeneration of articular chondrocytes. However, there are still some practical problems that need to be solved for the widespread use of bone morphogenetic proteins in cartilage regeneration, such as the safety of drug transporters, the lack of effective biological scaffold materials, the optimal dosage and time point of use of biological agents, and their toxic and side effects. Future research will focus on how to solve the above problems. The widespread application of bone morphogenetic proteins will open a new era for targeted treatment of cartilage damage and cartilage degenerative diseases represented by osteoarthritis.

Difference of Isokinetic Angle-Specific Moment Curves in Anterior Cruciate Ligament-injured Patients with or without Patellofemoral Articular Cartilage Injury / 中国康复理论与实践

Objective:To investigate the difference of isokinetic angle-specific moment curves between anterior cruciate ligament (ACL)-injured patients with and without patellofemoral cartilage injury (PFCI). Methods:A retrospective analysis was performed on patients underwent knee arthroscopy and isokinetic muscle strength testing before surgery from September, 2018 to September, 2019. Seventeen ACL-injured patients with PFCI and 17 ACL-injured patients without PFCI who matched in age, sex and meniscus injury were selected. Before arthroscopy, isometric and isokinetic strength of knee flexion and extension at velocity of 180°/s and 60°/s was tested by isokinetic dynamometer. Normalized torque-angle curves (torque/body mass) were generated in steps of 1° and the differences in angle-specific moment curves between two groups were compared. Results:At 180°/s, there was no significant difference in flexion isokinetic torque both healthy side and affected side between two groups (P >0.05); and no difference in extension torque of the healthy side (P >0.05), however, there was significant difference in extension torque of the affected side at 88° to 90° between two groups (t > 2.102, P <0.05). At 60°/s, there was significant difference in flexion torque of the healthy side at 62° to 82° between two groups (|t| >2.056, P <0.05), and no significant difference was found in flexion torque of the affected side (P >0.05), nor in extension torque of both sides between two groups (P > 0.05). A curve change was found at the beginning of the flexion and extension isokinetic moment curves at the velocity of 180°/s. The isometric knee extension torque was significantly different in the affected side between two groups (t = 2.858, P < 0.01), and no difference was found in isometric knee flexion torque in the affected side as well as both extension and flexion torques in the healthy side between two groups (t < 1.905, P > 0.05). Conclusion:The lower the isokinetic speed, the more significant the difference of strength is between ACL-injury patients with and without PFCI. High speed exercise is recommended for ACL-injured patients with PFCI.

Effectiveness of arthroscopic microfracture combined with osteochondral autologous transplantation for large area cartilage injury of femoral condyle of knee / 中国修复重建外科杂志

Objective: To explore the effectiveness of arthroscopic microfracture combined with osteochondral autologous transplantation (OAT) in treatment of large area (4-6 cm 2) cartilage injury of the femoral condyle of knee. Methods: Between March 2016 and June 2017, 22 patients of large area cartilage injury of the femoral condyle of knee were treated with arthroscopic microfracture combined with OAT. There were 16 males and 6 females with an average age of 22-60 years (mean, 38.6 years). The cause of injury was traffic accident in 8 cases and sports injuries in 14 cases. The disease duration was 1-6 months (mean, 3.4 months). There were 15 cases of medial femoral condyle injuries and 7 cases of lateral condyle injuries. The area of cartilage defect was 4-6 cm 2 (mean, 4.98 cm 2). According to the International Cartilage Repair Society (ICRS) classification, 9 cases were rated as grade Ⅲ and 13 cases as grade Ⅳ. Eighteen cases were combined with meniscus injuries. Preoperative visual analogue scale (VAS) score was 6.36±1.25 and Lysholm score was 36.00±7.77. Results: All incisions healed by first intention. All patients were followed up 2-3 years with an average of 2.3 years. At 2 years after operation, the VAS score was 1.27±0.94 and the Lysholm score was 77.82±6.21, which were significantly improved when compared with those before operation ( t=16.595, P=0.000; t=21.895, P=0.000). At 2 years after operation, MRI showed that the cartilage defect was repaired well. Conclusion: Arthroscopic microfracture combined with OAT can be used to treat large area cartilage injury of the femoral condyle of knee, and the good early effectiveness can be obtained.

Effect of psammosilene gavage on the expression of apoptosis-related proteins in chondrocytes of a rabbit osteoarthritis model / 中国组织工程研究

BACKGROUND: Psammosilene Capsule is a traditional Miao medicine formula that consists of Psammosilene tunicoides and Schefflera kwangsiensis. Psammosilene Capsule has been shown to hold protective effect on cartilage, but the underlying mechanism remains unclear. OBJECTIVE: To explore the possible mechanism of Psammosilene gavage in the treatment of osteoarthritis. METHODS: Ten of the 40 rabbits were randomly selected as the blank control group. The remaining 30 rabbits were used to establish the osteoarthritis model in the right hind knee of the rabbit by the modified Hulth method, and then were randomly divided into model (n=10), Psammosilene gavage (n=10), and p38 inhibitor (n=10) groups. At 7 days after modeling, the Psammosilene gavage group was fed with Psammosilene (57.5 mg/kg per day, p38 inhibitor group was injected with p38 inhibitor into the right hind knee joint (SB203580, 10 μmol/L, 0.5 mL), once weekly. The blank control and model groups were given the same amount of clean water, once daily. After 8 weeks, all animals were sacrificed to remove the right hind knee femoral condyle and tibial plateau. Severity of cartilage injury was evaluated by Pelletier score. Cartilage degeneration was examined by hematoxylin-eosin staining, saffron O staining and Mankin score. The expression levels of P-p38 and Cleaved Caspase-3 protein in cartilage tissue were detected by western blot assay. The expression levels of Bcl-2 and Bax mRNA in cartilage tissues were detected by quantitative real-time PCR. RESULTS AND CONCLUSION: (1) Compared with the Psammosilene gavage group, the model and p38 inhibitor groups had significantly increased Pelletier and Mankin scores (P < 0.05). (2) Compared with the Psammosilene gavage group, the expression levels of Bax mRNA and Cleaved Caspase-3 protein in the cartilage tissue in the model and p38 inhibitor groups were significantly increased (P < 0.05). (3) Compared with the Psammosilene gavage group, the expression level of Bcl-2 mRNA in the cartilage tissue in the model and p38 inhibitor groups was significantly decreased (P < 0.05). (4) Compared with the Psammosilene gavage group, the expression level of P-p38 protein in the model and p38 inhibitor groups was significantly increased (P < 0.05). (5) Our findings suggest that Psammosilene can inhibit the expression of apoptosis-related proteins and P-p38 protein in cartilage tissue, and then delay the degeneration of articular cartilage in the rabbit osteoarthritis model.

Role and significance of anterior cruciate ligament injury in the development of post-traumatic knee osteoarthritis / 中国组织工程研究

BACKGROUND: Anterior cruciate ligament has the function of stabilizing the knee joint and restricting the tibiofemoral joint in the translation and rotation of the tibia. Most patients with anterior cruciate ligament reconstruction have an increased risk of knee pain and knee instability. Knee osteoarthritis after trauma is a serious complication of anterior cruciate ligament injury. Knee osteoarthritis is a chronic progressive disease, and the mechanism of osteoarthritis after anterior cruciate ligament injury remains unclear. OBJECTIVE: To review the relationship between anterior cruciate ligament injury and the risk factors of post-traumatic knee osteoarthritis, so as to provide guidance for the treatment of post-traumatic knee osteoarthritis. METHODS: The first author searched related articles in PubMed database from the establishment of the database to October 2019. The key words were “ACL injury, traumatic knee osteoarthritis, ACL reconstruction, meniscus status, body mass index, cartilage injury, age, graft selection, time interval between injury and surgery”. A total of 123 articles were retrieved, and 66 articles were eligible for the inclusion criteria. RESULTS AND CONCLUSION: (1) Meniscus status, body mass index, cartilage damage, age, graft selection, and time between injury and surgery may influence the development of post-traumatic knee osteoarthritis. (2) Although anterior cruciate ligament reconstruction is primarily performed to restore stability after anterior cruciate ligament rupture, a long-term goal of the process is to reduce the risk of knee osteoarthritis and maintain long-term joint health. (3) Meniscus resection in patients with anterior cruciate ligament rupture accompanied by meniscus injury is also the cause of knee osteoarthritis, which is likely to be caused by weakened endurance and kinematic changes of the joint.

Application potential of CD146 positive subpopulation as seed cells for cartilage tissue engineering / 中国组织工程研究

BACKGROUND: The development of regenerative medicine and the appearance of tissue engineering technology provide a new solution for cartilage defect reconstruction. In tissue engineering, mesenchymal stem cells are widely used seed cells. However, as a heterogeneous cell group, stem cells play different roles in different subsets. Therefore, the application of key functional subsets of mesenchymal stem cells in cartilage repair has a broad application prospect. OBJECTIVE: To sort CD146 positive subpopulation cells from human adipose-derived mesenchymal stem cells to verify their biological characteristics and potential as seed cells in cartilage tissue engineering. METHODS: Human adipose-derived mesenchymal stem cells were provided by Zhejiang Jinshidai Biotechnology Co., Ltd. Surface markers of human adipose-derived mesenchymal stem cells were identified by flow cytometry. CD146 positive subpopulation cells were sorted from human adipose-derived mesenchymal stem cells using magnetic-activated cell sorting. Molecular characteristics of two kinds of cells were analyzed by gene chip detection technology and bioinformatics analysis technology. Two kinds of cells were induced to chondrocytes in vitro and histologically examined. Cell viability and apoptosis of two kinds of cells were detected before and after cryopreservation. RESULTS AND CONCLUSION: Human adipose-derived mesenchymal stem cells highly expressed stem cell-associated markers CD73 and CD90, but did not express hematopoietic stem cell-associated markers CD34, CD45, and HLA-DR. Bioinformatics analysis results showed that CD146 positive subpopulation had different functions in inflammatory pathways and musculoskeletal diseases compared with human adipose-derived mesenchymal stem cells. CD146 positive subpopulation could differentiate into cartilage, and its chondrogenic differentiation ability was better than that of human adipose-derived mesenchymal stem cells. CD146 positive subpopulation had better apoptosis and activity than human adipose-derived mesenchymal stem cells after resuscitation. These results suggest that CD146 positive subpopulation has good chondrogenic differentiation potential and is a promising seed cell for cartilage tissue engineering.

Arthroscopic osteochondral autografts with wenyang yisui recipe for repairing cartilage lesions of the knee / 中国组织工程研究

BACKGROUND: Wenyang Yisui Recipe is developed based on Yougui Pills according to many years of clinical practice. The clinical application of Wenyang Yisui Recipe in the treatment of early knee osteoarthritis as a prophylactic and therapeutic treatment has achieved favorable clinical effect. OBJECTIVE: To investigate the clinical efficacy of Wenyang Yisui Recipe combined with arthroscopic osteochondral autografts in the treatment of cartilage lesions of the knee. METHODS: Eighty-three patients under arthroscopic osteochondral autografts for cartilage lesions of the knee were enrolled, including 49 males and 34 females, aged 40 to 67 years old, with an average of (50.2±4.8) years old. The course of disease ranged from 1 to 27 months, with an average of (12.3±5.2) months. According to the Doll’s method, all the patients were divided into study group and control group. The patients in the study group received arthroscopic osteochondral autografts, followed by oral Wenyang Yisui Recipe, 300 mL per day in two divided doses, beginning at 2 days postoperatively for 2 continuous weeks as a session, three sessions in total. The control group only undertook arthroscopic osteochondral autografts. The Lysholm score and visual analogue scale score were used for assessing the knee function and pain, respectively, before surgery and 3 months after surgery. The study protocol was implemented in line with the relevant ethical requirements of Wang Jing Hospital, China Academy of Chinese Medical Sciences in February 2014 (approval No. 221). RESULTS AND CONCLUSION: All patients were followed up for 3 months after surgery. The study group was superior to the control group in the improvement of knee joint pain and swelling score at 3 months after surgery, and the intergroup difference was statistically significant (P < 0.05). The visual analogue scale score was significantly better in the study group than the control group at 3 months after surgery (P < 0.001). The visual analogue scale scores in the two groups were both improved at 3 months after surgery (P < 0.001). Therefore, arthroscopic osteochondral autografts combined with oral Wenyang Yisui Recipe can significantly ameliorate knee pain and function, with definite clinical effects.

Regulation of stem cells by transforming growth factor Β3/polylactic acid-glycolic acid microspheres / 中国组织工程研究

BACKGROUND: Transforming growth factor Β3/polylactic acid-glycolic acid (TGF-Β3/PLGA) sustained-release microspheres can maintain the effective drug concentration at the site of action and provide the feasibility for efficient utilization of growth factors. OBJECTIVE: To optimize the manufacturing process of TGF-Β3/PLGA sustained-release microspheres, and investigate their effects on the proliferation and migration of rabbit adipose-derived mesenchymal stem cells (ADSCs). METHODS: TGF-Β3/PLGA sustained-release microspheres were prepared by emulsification-solvent evaporation method. The morphology, particle size, drug spatial distribution, encapsulation efficiency, drug loading, and sustained release properties of the microspheres were characterized. The TGF-Β3/PLGA sustained-release microspheres were dissolved in phosphate buffered saline. The concentration of TGF-Β3 in the supernatant was detected at the corresponding time points. The microsphere morphology was observed by scanning electron microscopy at the corresponding time point. Adipose-derived mesenchymal stem cells were divided into six groups and then cultured with single culture medium (negative control) or culture medium containing TGF-Β3 or blank PLGA, or culture medium containing 10,100,1 000 g/L TGF-Β3/PLGA microspheres. Cell proliferation was detected by CCK-8 assay at the corresponding time point. Cells in each group were cultured for 24 hours with corresponding medium in a non-contact manner. The number of migratory cells was counted. RESULTS AND CONCLUSION: (1) TGF-Β3/PLGA sustained-release microspheres were spherical with smooth surface, no adhesion, and evenly distributed particle size. The microspheres had a diameter of 2-50 µm, and the protein drugs in the microspheres were evenly distributed, with high encapsulation efficacy and encapsulation dose. (2) The TGF-Β3/PLGA sustained-release microspheres had good degradation properties and were completely degraded after 6 months in vitro. At the same time, these microspheres had good sustained-release performance and released TGF-Β3 slowly for 45 days in vitro. (3) Blank microspheres and the sustained-release microspheres containing TGF-Β3 had no effect on the proliferation of adipose-derived mesenchymal stem cells. (4) Blank microspheres had no effect on the migration of adipose-derived mesenchymal stem cells, and the transforming growth factor 3 and the sustained-release microspheres containing TGF-Β3 promoted the migration of adipose-derived mesenchymal stem cells. There was no significant difference in the migration promotion between different concentrations of TGF-Β3. (5) These findings suggest that the TGF-Β3/PLGA sustained-release microspheres can promote the migration of adipose-derived mesenchymal stem cells without affecting their proliferation.

Comparison of arthroscopic osteochondral autologous transplantation for articular cartilage injury in young and middle-aged patients / 中国修复重建外科杂志

Objective: To compare the effectiveness of arthroscopic osteochondral autologous transplantation (OAT) in the treatment of young and middle-aged patients with the articular cartilage injury. Methods: A clinical data of 43 patients (43 knees) with articular cartilage injury, who underwent OAT between January 2008 and August 2016, was retrospectively analyzed. There were 23 patients aged 20-40 years (young group) and 20 patients aged 40-60 years (middle-aged group). The difference in age between the two groups was significant ( t=14.120, P=0.001). There was no significant difference in gender, body mass index, complications, affected side, lesion site, lesion area, and the International Cartilage Repair Society (ICRS) grade of cartilage injury between the two groups ( P>0.05). The function of knee joint was evaluated by Lysholm score and International Knee Documentation Committee (IKDC) score during the follow-up. MRI examination was performed to observe the repair of both receiving and the donor sites. Results: All the incisions in the two groups were healed by first intention. All patients in the two groups were followed up with an average of 3.6 years (range, 2-8 years). At 2 years after operation, the Lysholm and IKDC scores were significantly improved in the two groups when compared with the preoperative scores ( P0.05). The MRI examination at 2 years after operation showed that both receiving and the donor sites healed well in the two groups. Conclusion: According to the texture, thickness, elasticity, and lesion area of the cartilage, arthroscopic OAT might be the first choice for the articular cartilage injury in middle-aged patients and can obtain the satisfactory short-term effectiveness.

Effects of cartilage progenitor cells and microRNA-140 on repair of osteoarthritic cartilage injury / 中国修复重建外科杂志

Objective: To summarize the effect of cartilage progenitor cells (CPCs) and microRNA-140 (miR-140) on the repair of osteoarthritic cartilage injury, and analyze their clinical prospects. Methods: The recent researches regarding the CPCs, miR-140, and repair of cartilage in osteoarthritis (OA) disease were extensively reviewed and summarized. Results: CPCs possess the characteristics of self-proliferation, expression of stem cell markers, and multi-lineage differentiation potential, and their chondrogenic ability is superior to other tissues-derived mesenchymal stem cells. CPCs are closely related to the development of OA, but the autonomic activation and chondrogenic ability of CPCs around the osteoarthritic cartilage lesion cannot meet the requirements of complete cartilage repair. miR-140 specifically express in cartilage, and has the potential to activate CPCs by inhibiting key molecules of Notch signaling pathway and enhance its chondrogenic ability, thus promoting the repair of osteoarthritic cartilage injury. Intra-articular delivery of drugs is one of the main methods of OA treatment, although intra-articular injection of miR-140 has a significant inhibitory effect on cartilage degeneration in rats, it also exhibit some limitations such as non-targeted aggregation, low bioavailability, and rapid clearance. So it is a good application prospect to construct a carrier with good safety, cartilage targeting, and high-efficiency for miR-140 based on articular cartilage characteristics. In addition, CPCs are mainly dispersed in the cartilage surface, while OA cartilage injury also begins from this layer, it is therefore essential to emphasize early intervention of OA. Conclusion: miR-140 has the potential to activate CPCs and promote the repair of cartilage injury in early OA, and it is of great clinical significance to further explore the role of miR-140 in OA etiology and to develop new OA treatment strategies based on miR-140.

Treatment and Research Progress of Articular cartilage injury in HT3SS / 中国综合临床

Objective Articular cartilage injury is one of the most common orthopedic diseases with high morbidity and morbidity,especially in the elderly. Articular cartilage injury causes degenerative changes of articular cartilage, such as osteoarthritis, which can lead to disability, pain during joint movement and deformation of bone and joint. The prevalence of osteoarthritis accounts for 10% ～12% of the total population in the world. It is a common disease. The prevalence of osteoarthritis has increased to 49. 7% for the elderly aged over 65 years old ( Statistics of the World Health Organization ( who) in 2010 show that with the development of social aging and obesity and other adverse factors,these figures will continue to rise. It is known that osteoarthritis is related to aging,trauma,genetic susceptibility,obesity and inflammation,but the specific cause of osteoarthritis has not been fully identified, which leads to many obstacles in clinical treatment of osteoarthritis. At present,most of the clinical and research work in this field is focused on the restoration of cartilage trauma. In this review, we summarize and discuss the methods of cartilage defect repair,as well as the hot spots and directions of future research work.

Current advances on surgical treatment for knee articular cartilage injuries / 中国骨伤

Chondral injuries are short of self-healing ability and need to surgical repair after articular cartilage injury. Conventional treatment includes debridement and drainage under arthroscope, micro-fracture, osteochondral autograft transplantation (OATS), mosaiplasty and osteochondral allografts (OCA), autologous chondrocyte implantation (ACI). Debridement and drainage could remove pain factor, and has advantages of simple operation, wide clinical application and early clinical effect. Micro-fracture and osteochondral autograft transplantation is suitable for small area of cartilage repair, while the further effect showed that fibrous cartilage permeated by drill could decrease postoperative clinical effect. Osteochondral autograft transplantation has better advantages for reconstruction complete of wear-bearing joint. Autologous chondrocyte implantation and allogeneic cartilage transplantation are suitable for large area of cartilage defect, postoperative survival of allogeneic cartilage transplantation is effected by local rejection reaction and decrease further clinical effect. Cartilage tissue engineering technology could improve repair quality of autologous chondrocyte implantation, and make repair tissue close to transparent cartilage, but has limit to combined subchondral bone plate, reactive bone edema, bone loss and bad axis of lower limb. New technology is applied to cartilage injury, and has advantages of less trauma, simple operation, rapid recover, good clinical effect and less cost;and could be main method for treat cartilage injury with surgical repair technology. How to improve repair quality with compression resistance and abrasive resistance are expected to be solved.