Cartilage Repair Capacity within a Single Full-Thickness Chondral Defect in a Porcine Autologous Matrix-Induced Chondrogenesis Model Is Affected by the Location within the Defect

Objective Large articular cartilage defects are a challenge to regenerative surgery. Biomaterial scaffolds might provide valuable support for restoration of articulating surface. The performance of a composite biomaterial scaffold was evaluated in a large porcine cartilage defect. Design Cartilage repair capacity of a biomaterial combining recombinant human type III collagen (rhCo) and poly-(l/d)-lactide (PLA) was tested in a porcine model. A full-thickness chondral defect covering the majority of the weightbearing area was inflicted to the medial femoral condyle of the right knee. Spontaneous cartilage repair and nonoperated healthy animals served as controls. The animals were sacrificed after a 4-month follow-up. The repair tissue was evaluated with the International Cartilage Repair Society (ICRS) macroscopic score, ICRS II histological score, and with micro-computed tomography. Additionally, histopathological evaluation of lymph nodes and synovial samples were done for toxicological analyses. Results The lateral half of the cartilage defect in the operated groups showed better filling than the medial half. The mean overall macroscopic score for the rhCo-PLA, spontaneous, and nonoperated groups were 5.96 ± 0.33, 4.63 ± 0.42, and 10.98 ± 0.35, respectively. The overall histological appearance of the specimens was predominantly hyaline cartilage in 3 of 9 samples of the rhCo-PLA group, 2 of 8 of the spontaneous group, and 9 of 9 of the nonoperated group. Conclusions The use of rhCo-PLA scaffold did not differ from spontaneous healing. The repair was affected by the spatial properties within the defect, as the lateral part of the defect showed better repair than the medial part, probably due to different weightbearing conditions.

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Intra-articular Injection of SHP2 Inhibitor SHP099 Promotes the Repair of Rabbit Full-thickness Cartilage Defect

10.21203/rs.3.rs-404838/v1 ◽

2021 ◽

Author(s):

Ziying Sun ◽

Xingquan Xu ◽

Zhongyang Lv ◽

Jiawei Li ◽

Heng Sun ◽

...

Keyword(s):

Wnt Signaling ◽

Cartilage Repair ◽

Normal Saline ◽

Cartilage Defect ◽

Cartilage Defects ◽

Therapeutic Drug ◽

Full Thickness ◽

Differentiation Potential

Abstract Background Cartilage repair has been a challenge in the field of orthopedics for decades, highlighting the great significance of investigating potential therapeutic drugs. In this study, we explored the effect of SHP2 inhibitor, SHP099, as a small molecule drug on cartilage repair.Methods Human synovial mesenchymal stem cells (SMSCs) were isolated and their three-way differentiation potential was examined. After treated with chondrogenic medium, the chondrogenic effect of SHP099 on SMSCs was examined by Western blot, qPCR, and immunofluorescence (IF). To explore chondrogenic effects of SHP099 in vivo, full-thickness cartilage defects with microfracture were constructed in the right femoral trochlear of New Zealand White rabbits. Intra-articular injection of SHP099 or normal saline were performed twice a week for 6 weeks. Cartilage repair were evaluated by hematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining. Immunohistochemistry (IHC) for collagen II (COL2) was also conducted to verify the abandance of cartilage extracellular matrix after SHP099 treatment. The mechanism involving yes associated protein (YAP) and WNT signaling was investigated in vitro.Result The SMSCs isolated from human synovium represented optimal multi-differentiation potential. SHP099 increased chondrogenic markers (SOX9, COL2) expression and decreased hypertrophic markers (COL10, RUNX2) in SMSCs. The inhibition of YAP and WNT signaling was also observed. Moreover, compared with the normal saline group at 6 weeks, intra-articular injection of SHP099 resulted in better defect filling which formed more hyaline cartilage-like tissue with more glycosaminoglycan (GAG) and COL2.Conclusion SHP099 promotes the repair of rabbit full-thickness cartilage defect, representing a potential therapeutic drug for cartilage repair.

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Allogeneic Umbilical Cord Blood–Derived Mesenchymal Stem Cell Implantation Versus Microfracture for Large, Full-Thickness Cartilage Defects in Older Patients: A Multicenter Randomized Clinical Trial and Extended 5-Year Clinical Follow-up

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967120973052 ◽

2021 ◽

Vol 9 (1) ◽

pp. 232596712097305

Author(s):

Hong-Chul Lim ◽

Yong-Beom Park ◽

Chul-Won Ha ◽

Brian J. Cole ◽

Beom-Koo Lee ◽

...

Keyword(s):

Clinical Trial ◽

Adverse Events ◽

Cartilage Repair ◽

Older Patients ◽

Cartilage Defects ◽

Full Thickness ◽

Phase 3 ◽

Randomized Controlled ◽

Cartilage Restoration

Background: There is currently no optimal method for cartilage restoration in large, full-thickness cartilage defects in older patients. Purpose: To determine whether implantation of a composite of allogeneic umbilical cord blood–derived mesenchymal stem cells and 4% hyaluronate (UCB-MSC-HA) will result in reliable cartilage restoration in patients with large, full-thickness cartilage defects and whether any clinical improvements can be maintained up to 5 years postoperatively. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A randomized controlled phase 3 clinical trial was conducted for 48 weeks, and the participants then underwent extended 5-year observational follow-up. Enrolled were patients with large, full-thickness cartilage defects (International Cartilage Repair Society [ICRS] grade 4) in a single compartment of the knee joint, as confirmed by arthroscopy. The defect was treated either with UCB-MSC-HA implantation through mini-arthrotomy or with microfracture. The primary outcome was proportion of participants who improved by ≥1 grade on the ICRS Macroscopic Cartilage Repair Assessment (blinded evaluation) at 48-week arthroscopy. Secondary outcomes included histologic assessment; changes in pain visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) score from baseline; and adverse events. Results: Among 114 randomized participants (mean age, 55.9 years; 67% female; body mass index, 26.2 kg/m2), 89 completed the phase 3 clinical trial and 73 were enrolled in the 5-year follow-up study. The mean defect size was 4.9 cm2 in the UCB-MSC-HA group and 4.0 cm2 in the microfracture group ( P = .051). At 48 weeks, improvement by ≥1 ICRS grade was seen in 97.7% of the UCB-MSC-HA group versus 71.7% of the microfracture group ( P = .001); the overall histologic assessment score was also superior in the UCB-MSC-HA group ( P = .036). Improvement in VAS pain, WOMAC, and IKDC scores were not significantly different between the groups at 48 weeks, however the clinical results were significantly better in the UCB-MSC-HA group at 3- to 5-year follow-up ( P < .05). There were no differences between the groups in adverse events. Conclusion: In older patients with symptomatic, large, full-thickness cartilage defects with or without osteoarthritis, UCB-MSC-HA implantation resulted in improved cartilage grade at second-look arthroscopy and provided more improvement in pain and function up to 5 years compared with microfracture. Registration: NCT01041001, NCT01626677 (ClinicalTrials.gov identifier).

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Arthroscopic International Cartilage Repair Society Classification System Has Only Moderate Reliability in a Porcine Cartilage Repair Model

The American Journal of Sports Medicine ◽

10.1177/0363546521998006 ◽

2021 ◽

pp. 036354652199800

Author(s):

Jani Puhakka ◽

Teemu Paatela ◽

Eve Salonius ◽

Virpi Muhonen ◽

Anna Meller ◽

...

Keyword(s):

Cartilage Repair ◽

Scoring System ◽

Femoral Condyle ◽

Intraclass Correlation ◽

Type Iii Collagen ◽

Intrarater Reliability ◽

Scoring Method ◽

International Cartilage Repair Society ◽

Made In

Background: The International Cartilage Repair Society (ICRS) score was designed for arthroscopic use to evaluate the quality of cartilage repair. Purpose: To evaluate the reliability of the ICRS scoring system using an animal cartilage repair model. Study Design: Controlled laboratory study. Methods: A chondral defect with an area of 1.5 cm2 was made in the medial femoral condyle of 18 domestic pigs. Five weeks later, 9 pigs were treated using a novel recombinant human type III collagen/polylactide scaffold, and 9 were left to heal spontaneously. After 4 months, the pigs were sacrificed, then 3 arthroscopic surgeons evaluated the medial femoral condyles via video-recorded simulated arthroscopy using the ICRS scoring system. The surgeons repeated the evaluation twice within a 9-month period using their recorded arthroscopy. Results: The porcine cartilage repair model produced cartilage repair tissue of poor to good quality. The mean ICRS total scores for all observations were 6.6 (SD, 2.6) in arthroscopy, 5.9 (SD, 2.7) in the first reevaluation, and 6.2 (SD, 2.8) in the second reevaluation. The interrater reliability with the intraclass correlation coefficient (ICC) for the ICRS total scores (ICC, 0.46-0.60) and for each individual subscore (ICC, 0.26-0.71) showed poor to moderate reliability. The intrarater reliability with the ICC also showed poor to moderate reliability for ICRS total scores (ICC, 0.52-0.59) and for each individual subscore (ICC, 0.29-0.58). A modified Bland-Altman plot for the initial arthroscopy and for the 2 reevaluations showed an evident disagreement among the observers. Conclusion: In an animal cartilage repair model, the ICRS scoring system seems to have poor to moderate reliability. Clinical Relevance: Arthroscopic assessment of cartilage repair using the ICRS scoring method has limited reliability. We need more objective methods with acceptable reliability to evaluate cartilage repair outcomes.

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Hepatocyte growth factor facilitates cartilage repair: Full thickness articular cartilage defect studied in rabbit knees

Acta Orthopaedica Scandinavica ◽

10.3109/17453679708996266 ◽

1997 ◽

Vol 68 (5) ◽

pp. 474-480 ◽

Cited By ~ 66

Author(s):

Shigeyuki Wakitani ◽

Kazuhiko Imoto ◽

Tomoatsu Kimura ◽

Takahiro Ochi ◽

Kunio Matsumoto ◽

...

Keyword(s):

Articular Cartilage ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Cartilage Repair ◽

Cartilage Defect ◽

Full Thickness ◽

Articular Cartilage Defect ◽

Hepatocyte Growth

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Particulated Juvenile Articular Cartilage (PJAC) Allograft for Treatment of Lateral Femoral Condyle defect in High-Performance Athletes

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967118s00055 ◽

2018 ◽

Vol 6 (6_suppl3) ◽

pp. 2325967118S0005 ◽

Cited By ~ 1

Author(s):

Gabriella Bucci ◽

Michael Begg ◽

Kevin Pillifant ◽

Steven B Singleton

Keyword(s):

Articular Cartilage ◽

Cartilage Defect ◽

High Performance ◽

Femoral Condyle ◽

Cartilage Lesion ◽

Lateral Femoral Condyle ◽

High Grade ◽

Chondral Defect ◽

Short Term ◽

High Level

Background: A relatively new technology for the treatment of high grade articular cartilage lesions is the implantation of particulated articular cartilage obtained from a juvenile allograft donor (PJAC).1-2 Previous studies have reported the ability of juvenile chondrocytes to migrate from cartilage explants after being secured in a cartilage defect.3 There is little in the literature to use as a reference with respect to the use of PJAC for high grade articular cartilage lesion of the lateral femoral condyle after a failure of treatment with a microfracture in the high level athlete. Objective: The aim of this report is to describe the technique of PJAC transplantation for the treatment of chondral lesions of the lateral femoral condyle and to report the short term outcomes in the high performance athlete. Methods: We present a case report of two patients who were treated in our clinic in December 2014. Case 1: 16 year old female Division 1 university soccer player, who one year prior to our index surgery underwent microfractures of a symptomatic lateral femoral condyle articular cartilage lesion without relief. Cae 2: 29 year old male professional tennis player (case 2) with a recurrent, symptomatic chondral defect on the lateral femoral condyle. The player had undergone multiple arthroscopic procedures on the same knee following an injury sustained while playing in the Australian Open, including a surgery 8 months prior to our index operation that had included lateral meniscal tear repair and microfractures. PJAC procedure consists of a minimal debridement and chondroplasty, performed arthroscopically. For these central lateral femoral condyle lesions, a mini-arthrotomy is created along the lateral parapatellar longitudinal axis over a length of about 3 cm. With the chondral defect localized and prepared, a thin fresh layer of fibrin glue is then applied. The PJAC graft is equally distributed in the defect with space in between the fragments so as not over-fill the defect. Then, a new fibrin glue layer is placed to cover the graft. The overall construct remains just below the level of the normal articular surface. The knee is cycled through the range of motion to ensure that the tissue construct is stable. We present images of the cartilage defect after debridement and the allograft implantation procedure. In addition we will submit an instructional video performed on a knee specimen. Results: Outcomes measured were: IKDC, Lysholm, and Tegner knee scores together with arc of motion of the joint. After 28 months follow up, patients had gained complete range of motion and significantly decreased pain. Improvement for each outcome measure used is reported. Conclusions: PJAC transplantation offers pain relief and improved short term outcomes in high level performance athletes. Both of our patients are back to practicing their sport with notable improvement in symptoms. No complications have been noted. Long-term data is not yet available. References: Am J Farr J, Tabet SK, Margerrison E, Cole BJ. Clinical, Radiographic, and Histological Outcomes After Cartilage Repair With Particulated Juvenile Articular Cartilage: A 2-Year Prospective Study. Sports Med. 2014 Jun;42(6):1417-25. Saltzman BM, Lin J, Lee S. Particulated Juvenile Articular Cartilage Allograft Transplantation for Osteochondral Talar Lesions. Cartilage. 2017 Jan;8(1):61-72. Arshi A, Wang D, Jones KJ. Combined Particulated Juvenile Cartilage Allograft Transplantation and Medial Patellofemoral Ligament Reconstruction for Symptomatic Chondral Defects in the Setting of Recurrent Patellar Instability. Arthrosc Tech. 2016 Oct 10;5(5)

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Autologous Costal Cartilage Graft—A New Method to Treat Articular Cartilage Defects: Case Report and Note of Surgical Technique

Joints ◽

10.1055/s-0039-1697609 ◽

2018 ◽

Vol 06 (04) ◽

pp. 246-250

Author(s):

Antonio Gigante ◽

Marco Cianforlini ◽

Luca Farinelli ◽

Riccardo Girotto ◽

Alberto Aquili

Keyword(s):

Articular Cartilage ◽

Femoral Condyle ◽

Costal Cartilage ◽

Donor Site ◽

Standard Technique ◽

Cartilage Defects ◽

Cartilage Graft ◽

Full Thickness ◽

Articular Cartilage Defects ◽

Costal Cartilage Graft

AbstractFull-thickness articular cartilage defects do not heal spontaneously. Several techniques have been developed to address this issue, but none resulted in the restitutio ad integrum of the articular cartilage. The most frequent sites of chondral lesion in the knee are medial femoral condyle and patella. The patellofemoral lesions are characterized by outcomes that are generally worse than those of tibiofemoral ones. To date, it has been well recognized the chondrogenic potential of rib perichondrium, and costal cartilage grafts have been extensively used in reconstructive surgery. Considering the need to find a gold standard technique to restore articular defect, we developed and here described a new technique to repair cartilage lesions of the knee using autologous costal cartilage graft with its perichondrium. This innovative surgical approach can be used to treat full thickness articular defects using autologous hyaline cartilage, making it possible to cover wide defects. This one step technique is low invasive, not technically demanding with minimal donor site morbidity and it has low costs. The long-term clinical efficacy of the method remains to be evaluated.

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Intra-articular injection of synovium-derived mesenchymal stem cells and hyaluronic acid promote regeneration of massive cartilage defects in rabbits

Central Asian Journal of Global Health ◽

10.5195/cajgh.2013.97 ◽

2014 ◽

Vol 2 ◽

Cited By ~ 1

Author(s):

Vyacheslav Ogay ◽

Miras Karzhauov ◽

Ainur Mukhambetova ◽

Eric Raimagambetov ◽

Nurlan Batpenov

Keyword(s):

Stem Cells ◽

Molecular Weight ◽

Mesenchymal Stem Cells ◽

Hyaluronic Acid ◽

Cartilage Defect ◽

Femoral Condyle ◽

Cartilage Regeneration ◽

Cartilage Defects ◽

Low Molecular Weight ◽

Defect Area

Introduction: The purpose of this study was to investigate whether intra-articular injection of synovium-derived mesenchymal stem cells (SD MSCs) with low molecular weight hyaluronic acid (HA) could promote regeneration of massive cartilage in rabbits.Material and methods: The SD MSCs were harvested from the knees of 10 Flemish giant rabbits, expanded in culture, and characterized. A reproducible 4-mm cylindrical defect was created in the intercondylar groove area using a kit for the mosaic chondroplasty of femoral condyle COR (De Puy, Mitek). The defect was made within the cartilage layer without destruction of subchondral bone. Two weeks after the cartilage defect, SD MSCs (2 × 106 cell/0.15 ml) were suspended in 0.5% low molecular weight HA (0.15 ml) and injected into the left knee, and HA solution (0.30 ml) alone was placed into the right knee. Cartilage regeneration in the experimental and control groups were evaluated by macroscopically and histologically at 10, 30, and 60 days.Results: On day 10, after intra-articular injection of SD MSCs, we observed an early process of cartilage regeneration in the defect area. Histological studies revealed that cartilage defect was covered by a thin layer of spindle-shaped undifferentiated cells and proliferated chodroblasts. In contrast, an injection of HA did not induce reparation of cartilage in the defect area. At 30 days, macroscopic observation showed that the size of cartilage defect after SD MSC injection was significantly smaller than after HA injection. Histological score was also better in the MSC- treated intercondylar defect. At 60 days after MSC treatment, cartilage defect was nearly nonexistent and looked similar to an intact cartilage.Conclusion: Thus, intra-articular injection of SD MSCs can adhere to the defect in the intercondylar area, and promote cartilage regeneration in rabbits.

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Pro chondrogenic effect of mesenchymal stromal cell-based treatment of chondral defects under physioxia in a novel ex vivo organ model

10.1101/2020.11.06.348177 ◽

2020 ◽

Author(s):

Andrea Schwab ◽

Alexa Buß ◽

Oliver Pullig ◽

Franziska Ehlicke

Keyword(s):

Cartilage Repair ◽

Ex Vivo ◽

Knee Injuries ◽

Treatment Strategies ◽

Collagen Type I ◽

Cartilage Defects ◽

Type I ◽

Full Thickness ◽

Secondary Osteoarthritis ◽

Chondral Defects

AbstractObjectiveHigh failure rates of (trauma induced) knee injuries highlight the need to improve current treatment strategies aiming to decrease the number of secondary osteoarthritis developed by patients in later stage [1-3]. In this controlled laboratory study the stimulative effect of mesenchymal stromal cells (MSC) on chondrocyte (CHON) extracellular matrix production was investigated in an ex vivo cartilage defect model (chondral vs. full thickness defects) cultured under normoxic (20 % O2) and physioxic (2 % O2) conditions.DesignPorcine CHON or co-culture of 20 % CHON and 80 % MSC (MIX) were embedded in collagen type I hydrogel, implanted into 4 mm diameter cartilage defects of osteochondral explants and cultured with tissue specific media without addition of TGF-β under normoxia and physioxia. Chondral defects were induced automatically, while full thickness defects were created with biopsy punch. After 28 days of culture, samples were histologically processed, and treatments outcome was evaluated using international cartilage repair society (ICRS)-II scoring.ResultsUnder physioxic conditions, cartilage repair scoring results of the MIX treatment (chondral 8.67 ± 2.42, full thickness 5.67 ± 1.21) were close to those of CHON treatment (chondral 8.17 ± 0.75, full thickness 7.33 ± 1.21). Overall, scoring results were higher in physioxia compared to normoxia conditions in chondral defects, but less or no prevalent for full thickness defects.ConclusionCo-culture of CHON with MSC represents a promising approach to stimulate chondrogenic repair and tissue formation in our ex vivo model and reduces total amount of CHON needed for cell-based treatment.

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Two-Year Follow-Up and Remodeling Kinetics of ChonDux Hydrogel for Full-Thickness Cartilage Defect Repair in the Knee

Cartilage ◽

10.1177/1947603518800547 ◽

2018 ◽

Vol 11 (4) ◽

pp. 447-457 ◽

Cited By ~ 5

Author(s):

Matthew T. Wolf ◽

Hong Zhang ◽

Blanka Sharma ◽

Norman A. Marcus ◽

Uwe Pietzner ◽

...

Keyword(s):

Articular Cartilage ◽

Femoral Condyle ◽

Significant Loss ◽

Knee Function ◽

Cartilage Defects ◽

Full Thickness ◽

Hydrogel Scaffold ◽

Fill Volume ◽

Kinetics Of ◽

Articular Cartilage Defects

Objective To determine performance and repair kinetics of the ChonDux hydrogel scaffold for treating focal articular cartilage defects in the knee over 24 months. Design This assessor-blinded trial evaluates ChonDux hydrogel scaffold implantation in combination with microfracture in 18 patients across 6 sites. Male and female patients 18 to 65 years of age with full-thickness femoral condyle defects 2 to 4 cm2 in area were enrolled. Eligible patients received ChonDux treatment followed by rehabilitation. Defect volume fill was evaluated after 3, 6 (primary outcome), 12, 18, and 24 months by assessor blinded magnetic resonance imaging (MRI) analysis. Secondary outcomes were T2-weighted MRI relaxation time and patient surveys via visual analogue scale (VAS) pain and International Knee Documentation Committee (IKDC) knee function scoring. Results ChonDux maintained durable tissue restoration over 24 months with final defect percent fill of 94.2% ± 16.3% and no significant loss of fill volume at any time points. Tissues treated with ChonDux maintained T2 relaxation times similar to uninjured cartilage between 12 and 24 months. VAS pain scoring decreased between 1 and 6 weeks, and IKDC knee function scores improved by approximately 30.1 with ChonDux over 24 months. Conclusion ChonDux treatment is a safe adjunct to microfracture therapy and promotes stable restoration of full thickness articular cartilage defects for at least 24 months.

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