Repair Of Articular Cartilage Injury Research Articles

Platelet Rich Plasma in the Repair of Articular Cartilage Injury: A Narrative Review.

ObjectiveThis paper reviews the research of platelet-rich plasma (PRP) in articular cartilage injury repair, to assess the mechanism, utilization, and efficacy of PRP in the treatment of articular cartilage injury, hoping to provide a theoretical basis for the clinical application of PRP in the future.Materials and MethodsA comprehensive database search on PRP applications in cartilage repair was performed. Among them, the retrieval time range of PRP in clinical trials of repairing knee cartilage injury was from January 1, 2021 to January 1, 2022. Non-clinical trials and studies unrelated to cartilage injury were excluded.ResultPRP can affect inflammation, angiogenesis, cartilage protection, and cellular proliferation and differentiation after articular cartilage injury through different pathways. In all, 13 clinical trials were included in the analysis.ConclusionPRP is an emergent therapeutic approach in tissue engineering. Most studies reported that PRP has a positive effect on cartilage injury, improving the joint function, meanwhile there is a lack of standardized standards. The technology of PRP in the repair and treatment of articular cartilage injury is worthy of further research.

Restorative procedures for articular cartilage in the ankle: state-of-the-art review

Articular cartilage is a highly specialised connective tissue that serves to lubricate joint surfaces and distribute loads across the joint. Injury to articular cartilage is a significant cause of pain and dysfunction that may eventually lead to osteoarthritis or degenerative arthrosis. Management of these injuries is complicated by the complex architecture and poor vascularity of this tissue. The field of articular cartilage restoration has evolved rapidly over the past several decades and current techniques offer promising results. However, despite the fast pace of progress in the treatment and repair of articular cartilage injury, a clear gold standard in management has yet to emerge. Current techniques for managing cartilage injuries discussed in this review include bone marrow stimulation, osteochondral transplantation, chondrocyte implantation, cell-based transplantation, biological augmentation and scaffold-based therapies. Heterogeneity in study design, including surgical procedures, lesion and patient characteristics, cell collection, biologics preparation protocols and outcome measures limits interpretation of results presented in the literature. Therefore, standardisation across research protocols and collaboration among centres will be necessary. This ‘state-of-the-art review’ presents the indications and techniques for managing ankle articular cartilage lesions, as well as future directions and geographical differences in management.

Advances in application of growth factors in stem cell cartilage tissue engineering

Natural degeneration or trauma of articular cartilage all can lead to its structural and functional damage. Without blood supply and nerve innervation, chondrocytes in the matrix lacunae obtain essential nutrients and excrete metabolites mainly through osmosis, finally leads to its low metabolic activity and difficulty in self-repair after injury. At present, drug conservative treatment and surgical operation are the main clinical treatment, but both of them can't meet the clinical needs well. The development of cartilage tissue engineering provides a new direction for the repair of articular cartilage injury, in which growth factors plays a very important role. Growth factors, together with seed cells and cell scaffolds, constitute the three elements for the construction of tissue-engineered cartilage. Among them, Growth factors can significantly promote cell proliferation and differentiation and induce their functions. Various growth factors synergistically mediate the differentiation of seed cells into chondrocytes. In recent years, stem cell cartilage tissue engineering developed rapidly, which has opened a new way for repair of articular cartilage damage due to its abundant cell resources, small damage to body itself, strong ability of proliferation and directional differentiation, biological repair and other prominent advantages. Different types of hydrogels and stem cells show different abilities to support chondrogenesis and require different growth factors to induce chondrocyte differentiation. Traditional growth factors for tissue engineering include transcription growth factor β, insulin-like growth factors, bone morphogenetic proteins, fibroblast growth factors and cartilage derived morphogenetic protein. Recently, some scholars found that platelet-rich plasma, platelet-rich fibrin, Kartogenin and Mechano-growth factor can also effectively induce chondrogenic differentiation of stem cells and maintain chondrocyte phenotype. In addition, some synthetic compounds such as dexamethasone and inorganic particles can also promote the differentiation of stem cells into cartilage. This article systematically summarized the new progress of the traditional growth factors, emphatically introduced the new discovered growth factors and some synthetic compounds and inorganic particles, which can induce stem cells into cartilage. Finally classified the different sources of stem cells and its suitable growth factors, and gave an outlook of the next research direction of growth factors.

Application of growth factor in repair of articular cartilage injury

The joint is an important athletic organ, and has special structure, i.e. no blood supply in the mature articular cartilage. Hence, once articular cartilage is damaged and is difficult to self-repair. Nowadays, there are several clinical methods for articular cartilage injury, such as micro-fracture, transplant of articular cartilage, replacement of articular cartilage and cartilage tissue engineering. But the repairing effects of these methods are unsatisfactory. Growth factors are biologically active substances that are synthesized by cells in vivo and can accelerate cell growth, promote cell proliferation and induce cell migration etc. There are many growth factors participate in the development of cartilage, such as fibroblast growth factor(FGF), bone morphogenetic protein(BMP), insulin-like growth factor(IGF) and so on. Some research showed that the addition of exogenous growth factor in articular cartilage repair can effectively promote the repair of articular cartilage injury. In this paper, the main growth factors used for articular cartilage injury repair were reviewed, and the functions of these factors in the development and the repair of articular cartilage were discussed. The problems of growth factors in the application of articular cartilage repair were analyzed. Key words: Articular cartilage injury; Repair; Chondrocyte; Growth factor

Implantation of a Novel Cryopreserved Viable Osteochondral Allograft for Articular Cartilage Repair in the Knee.

Restoration and repair of articular cartilage injuries remain a challenge for orthopaedic surgeons. The standard first-line treatment of articular cartilage lesions is marrow stimulation; however, this procedure can often result in the generation of fibrous repair cartilage rather than the biomechanically superior hyaline cartilage. Marrow stimulation is also often limited to smaller lesions, less than 2 cm 2 . Larger lesions may require implantation of a fresh osteochondal allograft, though a short shelf life, size-matched donor requirements, potential challenges of bone healing, limited availability, and the relatively high price limit the wide use of this therapeutic approach. We present a straightforward, single-stage surgical technique of a novel reparative and restorative approach for articular cartilage repair with the implantation of a cryopreserved viable osteochondral allograft (CVOCA). The CVOCA contains full-thickness articular cartilage and a thin layer of subchondral bone, and maintains the intact native cartilage architecture with viable chondrocytes, growth factors, and extracellular matrix proteins to promote articular cartilage repair. We report the results of a retrospective case series of three patients who presented with articular cartilage lesions more than 2 cm 2 and were treated with the CVOCA using the presented surgical technique. Patients were followed up to 2 years after implantation of the CVOCA and all three patients had satisfactory outcomes without adverse events. Controlled randomized studies are suggested for evaluation of CVOCA efficacy, safety, and long-term outcomes.

An in situ photocrosslinkable platelet rich plasma - Complexed hydrogel glue with growth factor controlled release ability to promote cartilage defect repair.

In this study, we have developed a photocrosslinkable platelet rich plasma (PRP) - complexed hydrogel glue (HNPRP) for cartilage regeneration. The in situ formed HNPRP hydrogel glue showed not only the controlled release ability of growth factors, but also strong tissue adhesiveness, which could resolve the current problems in clinical application of PRP. Furthermore, HNPRP hydrogel glue could promote integrative hyaline cartilage regeneration, and its reparative efficacy for cartilage defect was better than thrombin activated PRP gel. This study provided not only an effective repair material for cartilage regeneration, but also developed an advanced method for PRP application.

Parathyroid Hormone-Induced Bone Marrow Mesenchymal Stem Cell Chondrogenic Differentiation and its Repair of Articular Cartilage Injury in Rabbits.

BackgroundWe explored the effect of parathyroid hormone (PTH)-induced bone marrow stem cells (BMSCs) complexed with fibrin glue (FG) in the repair of articular cartilage injury in rabbits.Material/MethodsForty-eight rabbits randomized into four groups were subjected to articular surgery (cartilage loss). The PTH and non-PTH intervention groups included transplantation with PTH/BMSC/FG xenogeneic and BMSC/FG xenogeneic complexes, respectively, into the injured area. The injured group contained no transplant while the control group comprised rabbits without any articular injury. Samples were monitored for cartilage repair up to three months post-surgery. Immunohistochemistry as well as real-time fluorescent quantitative PCR and Western blot were used to analyze the expression of type II collagen and aggrecan in the repaired tissue.ResultsAt 12 weeks post-surgery, the loss of articular cartilage in the PTH group was fully repaired by hyaline tissue. Typical cartilage lacunae and intact subchondral bone were found. The boundary separating the surrounding normal cartilage tissue disappeared. The gross and International Cartilage Repair Society (ICRS) histological ranking of the repaired tissue was significantly higher in the PTH intervention group than in the non-PTH intervention and injury groups (p<0.05) without any significant difference compared to the control group (p>0.05). Type II collagen and aggrecan stained positive and the average optical density, relative mRNA expression and protein-integrated optical density in the PTH group were higher than in non-PTH and injured groups (p<0.05) but not significantly different from the control group (p>0.05).ConclusionsPTH/BMSC/FG xenogeneic complexes effectively repaired the loss of cartilage in rabbit knee injury.

Cartilage tissue engineering: Role of mesenchymal stem cells along with growth factors & scaffolds.

Articular cartilage injury poses a major challenge for both the patient and orthopaedician. Articular cartilage defects once formed do not regenerate spontaneously, rather replaced by fibrocartilage which is weaker in mechanical competence than the normal hyaline cartilage. Mesenchymal stem cells (MSCs) along with different growth factors and scaffolds are currently incorporated in tissue engineering to overcome the deficiencies associated with currently available surgical methods and to facilitate cartilage healing. MSCs, being readily available with a potential to differentiate into chondrocytes which are enhanced by the application of different growth factors, are considered for effective repair of articular cartilage after injury. However, therapeutic application of MSCs and growth factors for cartilage repair remains in its infancy, with no comparative clinical study to that of the other surgical techniques. The present review covers the role of MSCs, growth factors and scaffolds for the repair of articular cartilage injury.

Influence of intra-articular administration of trichostatin a on autologous osteochondral transplantation in a rabbit model.

Autologous osteochondral transplantation (AOT) is a method for articular cartilage repair. However, several disadvantages of this method have been reported, such as transplanted cartilage degeneration and the lack of a connection between the grafted and adjacent cartilage tissues. To evaluate the effect of intra-articular administration of trichostatin A (TSA) on AOT, we conducted a case control study in a rabbit model. International Cartilage Repair Society (ICRS) macroscopic scores, the modified O'Driscoll histology scores, and real-time PCR were utilized to evaluate the results. At 4 weeks, both macroscopic and histological assessments showed that there was no significant difference between the TSA and control groups. However, the mean macroscopic and histological scores for the TSA-treated group were significantly higher than the scores for the control group at 12 weeks. TSA was shown to directly reduce collagen type II (COL2), aggrecan, matrix metalloproteinase (MMP), and a disintegrin and metalloproteinase domain with thrombospondin motifs 5 (ADAMTS-5) expression and to simultaneously repress the upregulation of MMP-3, MMP-9, and MMP-13 levels induced by interleukin 1β (IL-1β) in chondrocytes. In conclusion, TSA protects AOT grafts from degeneration, which may provide a benefit in the repair of articular cartilage injury.

An Autologous Tissue Implant, NeoCart, for Treatment of Hyaline Cartilage Injury in the Knee

NeoCart is an autologous cartilage tissue–engineered implant designed for use in repair of articular cartilage injuries. It uniquely combines a type I bovine-derived collagen scaffold with autogenous chondrocytes and bioreactor treatment. It is currently in the third phase of an investigational study in the United States for treatment of symptomatic articular cartilage lesions of the distal femur. This multicenter, prospective, randomized controlled trial directly compares changes of multiple patient-reported outcome measures over 3 years with a control group undergoing microfracture surgery. This article describes the study design and indications for enrollment in the phase III trial. The technical elements of NeoCart culture and production process, surgical implantation procedure, and rehabilitation guidelines are outlined. In addition, we review previously published findings from the completed phase I safety and phase II exploratory trials.

The effects of low intensity pulsed ultrasound on repair of articular cartilage injury in rabbits

Objective To investigate the effects of low intensity pulsed ultrasound ( LIPU ) on articular car-tilage injury in rabbits. Methods Ten adult New Zealand white rabbits with bilateral, full-thickness osteochondral defects in the cartilage surfaces of intercondylar fossas were used as model. The left knees in these rabbits treated with LIPU were used as experimental group. The right knees treated with sham intervention were used as controls. All the rabbits were sacrificed at the 8th week postoperation for gross appearance grading, histological grading and semi-quan-titation of proteoglycan in the repairing tissue. Results Compared with controls, defects treated with LIPU im-proved significantly as shown by gross appearance grades, histological grades and optical density of toluidine blue at the 8th week postoperation (both P <0.05). Conclusion LIPU could accelerate repairing of articular cartilage in-jury. Key words: Low intensity pulsed ultrasound; Cartilage; Injury; Repair

Adenovirus-mediated expression of growth and differentiation factor-5 promotes chondrogenesis of adipose stem cells

The repair of articular cartilage injuries is impeded by the avascular and non-innervated nature of cartilage. Transplantation of autologous chondrocytes has a limited ability to augment the repair process due to the highly differentiated state of chondrocytes and the risks of donor-site morbidity. Mesenchymal stem cells can undergo chondrogenesis in the presence of growth factors for cartilage defect repair. Growth and differentiation factor-5 (GDF5) plays an important role in chondrogenesis. In this study, we examined the effects of GDF5 on chondrogenesis of adipose-derived stem cells (ADSCs) and evaluate the chondrogenic potentials of GDF5 genetically engineered ADSCs using an in vitro pellet culture model. Rat ADSCs were grown as pellet cultures and treated with chondrogenic media (CM). Induction of GDF5 by an adenovirus (Ad-GDF5) was compared with exogenous supplementation of GDF5 (100 ng/ml) and transforming growth factor-β (TGF-β1; 10 ng/ml). The ADSCs underwent chondrogenic differentiation in response to GDF5 exposure as demonstrated by production of proteoglycan, and up-regulation of collagen II and aggrecan at the protein and mRNA level. The chondrogenic potential of a one-time infection with Ad-GDF5 was weaker than exogenous GDF5, but equal to that of TGF-β1. Stimulation with growth factors or CM alone induced transient expression of the mRNA for collagen X, indicating a need for optimization of the CM. Our findings indicate that GDF5 is a potent inducer of chondrogenesis in ADSCs, and that ADSCs genetically engineered to express prochondrogenic growth factors, such as GDF5, may be a promising therapeutic cell source for cartilage tissue engineering.

Cartilage repair with autogenic perichondrium cell and polylactic acid grafts.

The repair of articular cartilage injuries remains a challenge, with many of the current therapeutic strategies based on the grafting or recruitment of chondrogenic tissues or cells. This 1-year study compared the repair of a 3.7-mm diameter by 3-mm deep osteochondral defect in the medial femoral condyle of 24 New Zealand White rabbits; the defect was obtained using an autogenic perichondrium cell polylactic acid composite graft with a contralateral control in which the osteochondral defect remained empty. To elucidate the effect of host immune responses on the repair process after perichondrium cell transplantation, the results of the autogenic perichondrium cell polylactic acid graft group were compared with those obtained in the authors' previous 1-year study of allogenic perichondrium cell polylactic acid composite grafts implanted in a similar model. One year after surgery, the repair site underwent gross inspection and histologic, histomorphometric, biochemical, and biomechanical analyses. The autogenic perichondrium cell polylactic acid graft group (92%) and the control group in which the osteochondral defect remained empty (88%) resulted in a high percentage of grossly acceptable repairs. The autogenic grafts appeared to augment the intrinsic healing capacity of the animals (as compared with the animals in the No Implant Group). The autogenic perichondrium cell polylactic and grafts improved the histologic appearance and percentage of Type II collagen of the cartilaginous repair tissue. Compared with allogenic grafts, the autogenic grafts had better reconstitution of the subchondral bone. However, the results of this experimental model suggest a suboptimal concentration of glycosaminoglycans in the neocartilage matrix, a depressed surface of the repair tissue, a histologic appearance that was not equivalent to that of normal articular cartilage, and reduced biomechanical properties for the repair tissue. The future application of growth factors to this model may yield a treatment that can be applied in the clinical arena.

Cartilage repair with autogenic perichondrium cell/polylactic acid grafts: a two-year study in rabbits.

The repair of articular cartilage injuries remains a challenge. In this 2-year study, osteochondral defects in the femoral condyles of five rabbits were repaired with an autogenic perichondrium cell/polylactic acid graft and compared with a contralateral control in which the defect remained empty. The rabbits in the group with the grafts had a higher percentage of biologically acceptable repairs (100%) than did those in the control group (80%). According to the histologic and histomorphometric analyses, the grafts augmented the intrinsic healing. Nonetheless, the results for the grafts were tarnished by a depressed repair surface and a histologic appearance not equivalent to that of normal cartilage. The application of growth factors to this model may yield a clinical treatment.

Considerations prior to surgical repair of articular cartilage injuries of the knee

The diagnosis and treatment of articular cartilage injuries of the knee has gained increased attention in recent years. With the advancement of surgical techniques such as autologous cultured chondrocyte implantation and ostoechondral plug transfer to repair the chondral defects, a more aggressive treatment approach has also been adopted. Inititiating a treatment for an articular cartilage defect, it is imperative to have a complete assessment of any nonstructural or structural abnormalities that may have contributed to the development of the defect. Nonstructural factors include genetic factors; metabolic, inflammatory, or developmental diseases; activity level; and body weight. Structural factors include malalignment and ligamentous and meniscal deficiencies. The failure to recognize and correct these abnormalities when possible causes the degeneration and eventual failure of the articular cartilage repair regardless of the surgical technique used.

Repair of articular cartilage injury following intra-articular chymopapain-induced matrix proteoglycan loss.

The intra-articular injection of 0.02, 0.2, or 2.0 mg of chymopapain (CP) into the knee of adolescent rabbits caused the loss of more than 50% of the proteoglycans (PGs) in the cartilaginous tissues within the joint. Sequential measurements of cartilage-derived keratan sulfate epitope in serum and analyses of articular cartilage slices 2 days after the injection revealed that 0.02 mg of CP was nearly as effective as higher doses (0.2 or 2.0 mg of CP) in causing the depletion. The degradation and depletion of PGs in articular cartilage were shown to be localized to the joint and did not affect articular cartilage in the contralateral knee joint (no injection) or other cartilaginous tissues in the body. On day 9, partial replenishment of the articular cartilage PGs had occurred, irrespective of the dose used, and the articular surface within the joint remained intact. However, by day 21, articular cartilage in joints injected with 2.0 mg of CP had begun to show progressive degenerative changes, and these changes became more severe with time. In contrast, joints injected with 0.2 mg of CP continued to repair successfully by the reestablishment of a matrix that retained its integrity and appeared to remain functional for at least 6 months. These results suggest that the model may prove useful for the study of the repair processes that follow matrix injury and severe depletion of PGs from the articular cartilage matrix.