Treatment of Chondral Defect of the Knee Joint - Current Methods, Possibilities of Using Cultured Mesenchymal Stem Cells.

Articular Cartilage: The Search for the Holy Grail of Treatment and Restoration

Incidence rate of articular cartilage injury is increasing. As cartilage is a highly differentiated tissue without direct supply of blood or nerve and has limited regeneration potential after injury, treatment of cartilage injury still poses a major challenge for both patients and orthopedic surgeons. Mesenchymal stem cells (MSCs) are a class of pluripotent stem cells with potent proliferative capacity and chondrogenic ability, and are being used to repair articular cartilage injury through tissue engineering. The aim of this article is to provide a comprehensive review of MSC transplantation for the treatment of articular cartilage injury. Key words: Cartilage; Repair; Mesenchymal stem cells; Tissue engineering

The goals of all orthopaedic surgeons treating articular cartilage injuries have been anatomic reduction and stable fixation of the articular cartilage surface with restoration of limb alignment and/or reestablishment of the joint stability, all while minimizing the risk of surgical complications. Recent developments in the study of articular cartilage injury have shown that there is a robust cellular response to joint injury. This response has been shown to involve the synoviocytes, chondrocytes, and osteocytes in and around the injured joint and if these responses are left unchecked, they can lead to the development of posttraumatic osteoarthritis (PTOA). Therefore, to predictably and successfully treat articular cartilage injuries, it is not sufficient to just restore articular congruity, limb alignment, and joint stability, but we must also recognize and attempt to mitigate this associated cellular response. Understanding not only the mechanical aspects of these joint injuries but also the biological aspects is paramount to giving our patients the best opportunity to heal their injuries, recover full function, and avoid the potential devastating development of PTOA. Gone is the simplistic view that if one can achieve articular congruity after intraarticular fracture, as well as joint stability after ligamentous injury, that our patients will do just fine. This review sheds new light on the molecular response to cartilage injury, how residual joint incongruity and instability affect the joint's ability to recover from injury, and how chondrocyte apoptosis in response to injury can influence joint. This article then briefly reviews how cellular and growth factors may be beneficial to the treatment of articular cartilage injury and how ultimately cartilage regeneration may be used in the future to salvage the joints ravaged by PTOA in response to injury.

ObjectiveThis paper reviews the research of platelet-rich plasma (PRP) in articularcartilage injury repair, to assess the mechanism, utilization, and efficacyof PRP in the treatment of articular cartilage injury, hoping to provide atheoretical basis for the clinical application of PRP in the future.Materials and MethodsA comprehensive database search on PRP applications in cartilage repair wasperformed. Among them, the retrieval time range of PRP in clinical trials ofrepairing knee cartilage injury was from January 1, 2021 to January 1, 2022.Non-clinical trials and studies unrelated to cartilage injury wereexcluded.ResultPRP can affect inflammation, angiogenesis, cartilage protection, and cellularproliferation and differentiation after articular cartilage injury throughdifferent pathways. In all, 13 clinical trials were included in theanalysis.ConclusionPRP is an emergent therapeutic approach in tissue engineering. Most studiesreported that PRP has a positive effect on cartilage injury, improving thejoint function, meanwhile there is a lack of standardized standards. Thetechnology of PRP in the repair and treatment of articular cartilage injuryis worthy of further research.

One of the major problems observed in veterinary practice is articular cartilage injuries in animals. In terms of agriculture, it leads to their culling from the herd, even if they are highly productive animals. With companion animals, owners usually have to decide between euthanasia or long-term sometimes lifelong treatment of the injury by a veterinarian. The use of mesenchymal stem cells (MSCs) for the treatment of cartilage injury in veterinary medicine is based on the good results observed in preclinical studies, where large animals have been used as experimental models to study the regenerative activity of MSCs. According to the literature, MSCs in veterinary medicine have been used to treat cartilage injury of dogs and horses, whereas sheep and goats are generally models for reproducing the disease in preclinical experimental studies.

Objective: This study aims to determine the clinical efficacy of articular cartilage injury repair surgery. Methods: A total of 112 patients with knee articular cartilage injury who received treatment at our hospital from August 2015 to May 2017 were selected as research subjects. The patients were divided into control and experimental groups (56 patients in each group) through random even-odd number method and treated with arthroscopic joint debridement and arthroscopic microfracture repair surgery, respectively. Clinical treatment effect, HSS score, complication, and surgical result satisfaction were observed and compared between the two groups. Results: Patients in the experimental group exhibited significantly higher total effective rate than those in the control group (P<0.05). The HSS score in the experimental group was higher than that in the control group, and more patients in the former group showed HSS score higher than 85 or between 60-85 and less patients had HSS score less than 60 (P<0.05). Patients in the control group experienced less satisfaction on the result of surgery and higher complication incidence rate than those in the experimental group; the difference was statistically significant between the two groups (P<0.05). Conclusion: Arthroscopic microfracture surgery exerts satisfactory treatment effect for knee articular cartilage injury and can significantly improve patient satisfaction regarding surgery result, improve the articular function and physical action ability of patients, and reduce the incidence rate of complications. Hence, this technique is a feasible option and must be promoted for clinical application.

Emerging Options for Treatment of Articular Cartilage Injury in the Athlete

Articular cartilage injury and degeneration occurs frequently in athletes and results from the significant chronic joint stress and acute traumatic injuries associated with high-impact sports. These injuries do not heal spontaneously and often lead to progressive painful impairment of joint function and limitation of sports participation. Untreated articular cartilage defects frequently lead to chronic joint degeneration and disability. Treatment of articular cartilage injury in athletes can be complex and requires effective and durable joint surface restoration that can withstand even the significant joint stresses generated during sports activity. Several established articular cartilage repair techniques have been shown to successfully return the athlete with articular cartilage injury to high-impact sports. In addition, novel treatment concepts and techniques that apply modern tissue engineering technologies promise further advancement in the treatment of these challenging injuries in the demanding athletic population.

The knee joint is the second largest joint in the human body, with a wide range of functional activities and strong support for the human body. Moreover, the cartilage of the knee joint is hyaline cartilage, which is relatively brittle, so it is most vulnerable to trauma. In clinical work, the damage of articular cartilage is a disease with a high rate of orthopedic visits. In this paper, all the experimental group cases included in the observation were patients with acute articular cartilage injury or OA diagnosed by knee arthroscopy. All experimental groups and control groups did not have any strenuous exercise one day before MRI (magnetic resonance imaging), and they sat for 30 minutes before the examination. Conventional scanning sagittal FSE-T1WI, FSE-T2WI, FS-FSE-T1WI, FS-FSE-T2WI, FS-PDWI, and coronal FS-PDWI sequence. In the normal control group, after the T2 color map was generated in the workstation, the articular cartilage was divided on the midsagittal plane, and the patellar cartilage and tibial plateau were roughly divided into upper, middle, lower and anterior, middle, and posterior thirds. In order to ensure the maximum comparability of the results, an artificial intelligence segmentation algorithm is used to divide the region of interest equally, and the central part of each partition is selected as much as possible for measurement. The T2 values of the three partitions of each cartilage were measured one by one and averaged. For the comparison results of T2 value of cartilage in the same part: according to patellar cartilage, femoral cartilage, and tibial cartilage, the P values are 0.973, 0.150, and 0.525, respectively. Therefore, early detection and early treatment of articular cartilage injury are of great significance to the performance of athletes' competition level and the extension of sports life.

Osteoarthritis (OA) is a debilitating joint condition affecting millions of people worldwide, triggering painful chondral defects (CDs) that ultimately compromise the overarching patients' quality of life. Currently, several reconstructive cartilage techniques (RCTs) (i.e.: matrix-assisted autologous chondrocytes implantation has been developed to overcome the total joint replacement limitations in the treatment of CDs. However, there is no consensus on the effectiveness of RCTs in the long term, as they do not provide adequate pro-regenerative stimuli to ensure complete CDs healing. In this study, we describe the biofabrication of an innovative scaffold capable to promote the CDs healing by delivering pro-regenerative hypoxic cues at the cellular/tissue level, to be used during RCTs. The scaffold is composed of a gelatin methacrylate (GelMA) matrix doped with hypoxic seeds of GelMA functionalized with a fluorinated oxadiazole (GelOXA), which ensures the delivery of hypoxic cues to human articular chondrocytes (hACs) embedded within the scaffold. We found that the GelMA/GelOXA scaffold preserved hACs viability, maintained their native phenotype, and significantly improved the production of type II collagen. Besides, we observed a reduction in type I and type X collagen, characteristic of unhealthy cartilage. These findings pave the way for the regeneration of healthy, hyaline-like cartilage, by delivering hypoxic cues even under normoxic conditions. Furthermore, the GelMA/GelOXA scaffold's ability to deliver healing signals directly to the injury site holds great potential for treating OA and related CDs, and has the potential to revolutionize the field of cartilage repair and regenerative medicine.

EMBO Reports (2019) e48172 Stem cell‐based regenerative medicine has experienced turbulent times in recent years that have involved several scandals implicating prominent institutions and numerous retractions of papers from leading journals. But it has also seen real progress being made on the way to the clinic. It reflects the tension between human ambition and hope on one side and the need for hard evidence and solid data on the other side in a field where early expectations ran far ahead of reality. This tension may help explain the recent scandal involving stem cell surgeon Paolo Macchiarini, who was found guilty of scientific misconduct regarding an article in The Lancet , which has since been retracted. It is an ongoing saga as Macchiarini is still publishing in leading journals, even though his reputation as a surgeon and stem cell researcher has been compromised. > … the whole field of regenerative medicine had been tainted by a number of cases where […] researchers had taken short cuts and neglected basic science. The story dates back to 2004, when Macchiarini's team extracted some pig intestine and removed the cells to leave a collagen matrix that was then repopulated with muscle and fibroblasts to generate connective epidermal tissue. The patch was implanted in the airway of a 58‐year‐old patient suffering from respiratory problems after surgery for lung cancer [1]. Macchiarini then expanded this technique to whole tracheas using plastic scaffolds in addition to natural tissue from human donors. In another clinical case, the bare plastic scaffold was populated with stem cells taken from the patient's own bone marrow and implanted in a young female patient in 2008. This propelled Macchiarini almost to rock star status and an appointment by the Karolinska Institute, where he refined his technique by replacing donor windpipes with plastic …

Background:The ability to return to football (soccer) presents a critical aspect for successful treatment of articular cartilage injury in the football (soccer) player.Methods:Information about sports participation after articular cartilage repair was collected from the literature. Special focus was placed on data in football athletes with information on return rate, timing of return, level of postoperative competition, and the ability to compete in the sport over time.Results:Twenty studies describing 1,469 athletes including football players with articular cartilage injury were reviewed. Average return to sport was 79% without a significant difference in return rate or postoperative level of play between cartilage repair techniques. Time to return varied between 7 to 17 months, with the longest time for autologous chondrocyte transplantation (ACI). Advanced sport-specific rehabilitation was able to reduce recovery time. Durability of results was best after ACI, with up to 96% continued sport participation after more than 3 years. Player age, time between injury and treatment, competitive level, defect size, and repair tissue morphology affected the ability to return to play. Sports participation after cartilage repair generally promoted joint restoration and functional recovery.Conclusions:Articular cartilage repair allows for a high rate of return to high-impact sports including football, often at the preinjury competitive level. The time of return and durability can be variable and depend on repair technique and athlete-specific factors. Advanced, sport-specific rehabilitation can facilitate return to football.

This review discusses the current perspectives and practices regarding the treatment of articular cartilage injury. Specifically, the authors have delineated and examined articular cartilage repair techniques as either surgical procedures or manufactured products. Although both methodologies are used to treat articular cartilage injury, there are obvious advantages and disadvantages to the application of both, with the literature providing few recommendations on the most suitable regimen for the patient and surgeon. In recent times, cell-based tissue engineering products, predominantly autologous chondrocyte implantation, have been the subject of much research and have become clinically popular. Herein, we review the most used procedures and products in cartilage repair, compare and contrast their outcomes, and evaluate the issues that must be overcome in order to improve patient efficacy in the future.

Articular cartilage injuries in the glenohumeral joint present a unique and difficult problem for the patient and surgeon alike. Various etiologies exist for the development of these cartilage lesions; therefore, treatment options are vast and must be chosen thoughtfully, especially in the young, active patient. Across all treatment modalities, the goal is for the patient to regain lasting function and mobility while decreasing pain.

TREATMENT OF OSTEOCHONDRAL INJURIES: Genetic Engineering