Treatment Of Large Cartilage Defects Research Articles

Effectiveness and Safety of Matrix-Associated Autologous Chondrocyte Implantation for the Treatment of Articular Cartilage Defects: A Real-World Data Analysis in Japan

Background: The effectiveness and safety of matrix-associated autologous chondrocyte implantation with an autologous periosteal flap (pMACI) remain unclear. The Japanese Ministry of Health, Labor, and Welfare requires postmarketing surveillance of all patients undergoing pMACI using the tissue-engineered product JACC. Purpose: To evaluate the effectiveness and safety of pMACI for large articular cartilage defects (≥4 cm2) in the knee joint using real-world data analysis. Study Design: Case series; Level of evidence, 4. Methods: Data were collected from patients who underwent pMACI between 2012 and 2019, with 2 years of follow-up. The primary outcomes were the Lysholm knee score and Knee injury and Osteoarthritis Outcome Score (KOOS) at 6, 12, and 24 months. Adverse events were assessed by physical examination, magnetic resonance imaging, and/or arthroscopy. Results: Overall, 232 knees in 225 patients who presented with trauma (198 knees) or osteochondritis dissecans (34 knees) in the medial (132 knees) and lateral (44 knees) femoral condyle, patella (25 knees), trochlea (86 knees), and tibial plateau (4 knees) were included. The mean age of the patients was 40.9 ± 15.0 years, with mean cartilage defects of 5.6 ± 2.4 cm2 in size. Concomitant surgeries, such as osteotomy (50 knees), ligament reconstruction (27 knees), meniscal procedures (28 knees), osteochondral autograft transplantation (24 knees), and microfracture (14 knees), were performed in 113 (48.7%) knees. The minimal clinically important difference in the Lysholm knee score and KOOS Symptoms subscale was achieved in 79.7% and 63.5% of patients, respectively, and the Patient Acceptable Symptom State was achieved in 90.1% and 73.7%, respectively. Substantial clinical benefit was achieved in the KOOS Sports/Recreation and Quality of Life subscales at 39.6% and 37.8%, respectively. Knees that underwent concomitant microfracture had significantly worse KOOS values than the remainder of the cohort. Complications, including effusion (16.8%), graft delamination (14.7%), knee contracture (9.1%), graft hypertrophy (8.2%), and ossification (3.4%), were observed in 86 (37.1%) knees. Osteochondritis dissecans was significantly associated with graft hypertrophy and ossification, whereas concomitant surgery was significantly associated with delamination and contracture. Treatment failure required additional cartilage procedures in 11 (4.7%) knees. Conclusion: Treatment of large cartilage defects (≥4 cm2) with pMACI resulted in improved outcome scores in approximately 75% of patients. However, complications occurred in one-third of patients, and 4.7% required reoperation.

Fresh Osteochondral Allograft Transplantation for Treatment of Large Cartilage Defects of the Femoral Head: A Minimum Two-Year Follow-Up Study of Twenty-Two Patients

BackgroundControversy remains over the surgical management of large osteochondral lesions of the femoral head in young, active patients. The purpose of this study is to assess midterm clinical and radiographic outcomes after fresh osteochondral allograft transplantation (OAT) for large femoral head lesions at minimum 2-year follow-up. MethodsA retrospective review of prospectively collected data was performed for 22 patients under the age of 50 years with defined femoral head osteochondral lesions who underwent fresh OAT between 2008 and 2015. Patients were assessed clinically using the modified Harris Hip Score (mHHS) preoperatively and at each follow-up visit. Postoperative radiographs were evaluated for graft integrity and Kellgren & Lawrence Grade for osteoarthritis severity. Complications and reoperation were assessed by chart review. Kaplan-Meier survivorship analyses with 95% confidence intervals were performed for the end point of conversion to total hip arthroplasty. ResultsAt a mean follow-up of 68.8 months (26-113), the mean mHHS improved significantly (P < .001) from 48.9 (19-84) to 77.4 (35-98). Sixteen of 22 patients (72.7%) had an mHHS ≥70 at the latest follow-up. Arthritic progression, as indicated by an increase in the Kellgren & Lawrence Grade, occurred in 4 of 22 hips (18.2%). Five patients (22.7%) underwent conversion to total hip arthroplasty. Graft survivorship was 86.4 ± 7.3% at 2 years, 78.5 ± 10.0% at 5 years, and 67.3 ± 13.5% at 9 years. ConclusionFresh OAT may be a viable treatment option for osteochondral defects of the femoral head in young, active patients with minimal preexisting joint deformity.

Delivery of nano curcumin from thermosensitive co-cross-linked chitosan hydrogels for the treatment of large cartilage defects of the knee

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Patient Factors Associated with Osteochondral Allograft Success in Knees with or without Co-morbidities

Objectives:To determine preoperative variables that may influence outcomes after osteochondral allograft transplantation for treatment of large cartilage defects in the knee.Methods:A retrospective review of 75 patients who underwent osteochondral allograft transplantation for large (>1 cm) grade IV cartilage defects in knees was performed. Patient variables evaluated included: smoking, workers compensation, BMI, pre-injury activity level (high level athlete, recreational athlete, active non-athlete, minimal activity, sedentary), number and type of co-morbidities in the operated knee (meniscal, ligament, and/or other cartilage pathology), lesion location (medial femoral condyle, lateral femoral condyle or multiple lesions), number of grafts placed (1, 2 or >2) and patients who underwent revision surgery related to OCA transplantation. Preoperative and postoperative VAS pain scores were used as the primary outcome measure. Success was defined as a VAS pain score of 0 or improvement in score (decrease) of 2 or more at final follow-up. The mean follow-up time was 19.5 months (3-53 months). Statistically significant (p<0.05) effects on successful outcomes were evaluated using Fisher's exact tests and odds ratios.Results:The study population was 41 males and 34 females with an average age of 34.2 years (14-61). 53 patients (71%) had successful outcomes. 59 patients (79%) had co-morbidities with the average being 2 comorbidities (1-4) per patient. 68% of patients with co-morbidities achieved a successful outcome versus 81% of patients with no co-morbidities, but this difference in proportions was not statistically significant (p=0.46). Active patients (HLA, REC, ACT) were significantly (p=0.023) and 4.5 times more likely to have a successful outcome than minimally active or sedentary patients. Patients with BMI <30 were 3.7 times more likely to have a successful result and the difference was significant (p=0.011). Smoking, workman's compensation, OCA-related revision surgery, lesion location and number of grafts placed did not have statistically significant effects on outcome.Conclusion:Osteochondral allograft transplantation can be a successful treatment option for large cartilage defects in the knee with patients having no intra-articular co-morbidities achieving an 81% success rate. Patients who are more active preoperatively and those with BMI <30 were significantly more likely to have successful outcomes.

Osteochondral autograft transplantation or autologous chondrocyte implantation for large cartilage defects of the knee: a meta-analysis.

Autologous chondrocyte implantation (ACI) and osteochondral autograft transplantation (OAT or mosaicplasty) are two effective surgeries for the treatment of large cartilage defects for more than two decades. But there are always some controversies about which one has the better outcomes for the patients. The purpose of this meta-analysis is to compare the outcomes of these two surgeries and give an advice to the clinical practices. The literature search was performed on multiple electronic databases with specific included criteria. After the assessments, five Randomized controlled trials (level II) were included and two of them were in the same cohort. The continuous data of outcomes were categorized into ranked ones (excellent, good, fair and poor) for comparisons. In the six comparisons of excellent or good results and poor results, the outcomes of ACI were significantly better than OAT in only one comparison (RR 2.57, 95 % CI 1.09-6.07, P = 0.03) while others had no significant differences. We may reach a primary conclusion that there is no significant different outcome between ACI and OAT in a short-term follow-up but it may indicate that the patients with OAT may be more likely to have worse condition than that with ACI for a long-term period.

Short-term follow up after implantation of a cell-free collagen type I matrix for the treatment of large cartilage defects of the knee.

Although there are various new scaffold-based techniques for cartilage regeneration it remains unclear up to which defect size they can be used. The present study reports of a cell-free collagen type I gel matrix for the treatment of large cartilage defects of the knee after a two-year follow-up. Twenty-eight patients with a mean cartilage defect size of 3.71 ± 1.93 cm² were treated with a cell-free collagen type I gel matrix (CaReS-1S®, Arthro Kinetics AG, Krems/Donau, Austria) via a mini-arthrotomy. Clinical outcome was assessed preoperatively and six weeks as well as six, 12 and 24 months after surgery using various clinical outcome scores (IKDC, Tegner, KOOS, VAS). Cartilage regeneration was evaluated via MRI using the MOCART score. Seventeen male and 11 female patients with a mean age of 34.6 years were included in this study. Significant pain reduction (VAS) could be noted after six weeks already. Patient activity (IKDC, Tegner) could be significantly improved from 12 months on and nearly reached reported pre-operative values. All subject categories of the KOOS except for symptom (swelling) showed significant improvements throughout the study. Constant significant improvements of the mean MOCART score were observed from 12 months on. MR images did not yield any signs of infection or synovitis. After 24 months a complete defect filling could be noted in 24 out of 28 cases with a mainly smooth surface, complete integration of the border zone and homogenous structure of the repaired tissue. Cell-free collagen type I matrices appear to be a safe and suitable treatment option even for large cartilage defects of the knee. Results of this study were comparable to the better-established findings for small cartilage defects. Mid- and long-term results will be needed to see if clinical and MR-tomographic outcome can be maintained beyond 24 months.

Hyaluronic Acid (800 kDa) Supplementation of University of Wisconsin Solution Improves Viability of Osteochondral Grafts and Reduces Matrix Metalloproteinase Expression during Cold Preservation.

Osteochondral allografting is a promising option for the treatment of large cartilage defects. However, because the cell viability of osteochondral tissues (OCTs) gradually reduces during storage at 4°C, methods for maintaining the cell viability of fresh OCTs are needed to improve transplantation outcomes. Here, we evaluated whether the supplementation of preservation solution with one of three different molecular weight forms of hyaluronic acid (HA) improved the viability of rat OCTs during long-term cold storage. The supplementation of University of Wisconsin (UW) solution with 800 kDa significantly improved the cell viability of OCT after 14 days at 4°C compared to nonsupplemented UW solution. In contrast, UW solution supplemented with either 1900 or 6000 kDa HA did not markedly improve the cell viability of the OCT. Real-time PCR analysis revealed that the levels of matrix metalloproteinases 2, 3, and 9 were significantly decreased in OCT stored in UW solution supplemented with 800 kDa HA. Although further studies in human OCT are warranted, these findings demonstrate that the use of 800 kDa HA in place of serum may be a suitable approach for the long-term preservation of osteochondral allografts designated for the repair of large cartilage defects in the clinical setting.

Hydrogen supplementation of preservation solution improves viability of osteochondral grafts.

Allogenic osteochondral tissue (OCT) is used for the treatment of large cartilage defects. Typically, OCTs collected during the disease-screening period are preserved at 4°C; however, the gradual reduction in cell viability during cold preservation adversely affects transplantation outcomes. Therefore, improved storage methods that maintain the cell viability of OCTs are needed to increase the availability of high-quality OCTs and improve treatment outcomes. Here, we evaluated whether long-term hydrogen delivery to preservation solution improved the viability of rat OCTs during cold preservation. Hydrogen-supplemented Dulbecco's Modified Eagles Medium (DMEM) and University of Wisconsin (UW) solution both significantly improved the cell viability of OCTs during preservation at 4°C for 21 days compared to nonsupplemented media. However, the long-term cold preservation of OCTs in DMEM containing hydrogen was associated with the most optimal maintenance of chondrocytes with respect to viability and morphology. Our findings demonstrate that OCTs preserved in DMEM supplemented with hydrogen are a promising material for the repair of large cartilage defects in the clinical setting.

Is the Transplant Quality at the Time of Surgery Adequate for Matrix-guided Autologous Cartilage Transplantation? A Pilot Study

Matrix-guided autologous chondrocyte transplantation (MACT) has been proposed as an option for treating large full-thickness cartilage defects. However, little is known about the chondrogenic potential of transplants for MACT at the time of implantation, although cell quality and chondrogenic differentiation of the implants are crucial for restoration of function after MACT. We therefore asked: (1) Do MACT implants allow deposition of extracellular cartilage matrix in an in vitro culture model? (2) Are these implants associated with improved knee function 1 year after MACT in large cartilage defects? We retrospectively reviewed all 125 patients with large localized cartilage defects (mean defect size 5 cm(2)) of the knee who were treated with MACT from 2005 to 2010. The mean age was 31 years (range, 16-53 years). Portions of the cell-matrix constructs (n = 50) that were not implanted in the cartilage defects were further cultured and tested for their potential to form articular cartilage. Knee function of all patients was analyzed preoperatively, 3 months, and 1 year postoperatively with the International Knee Documentation Committee (IKDC) score. In vitro assessment of the cell-matrix implants showed chondrogenic differentiation with positive staining for glycosaminoglycans and collagen II in all cultures. Enzyme-linked immunosorbent assay showed an increase of collagen II production. We observed an improvement in median IKDC score from 41 to 67 points at last followup. Cartilage extracellular matrix deposition shows adequate implant quality for MACT at the time of implantation and justifies the use for treatment of large cartilage defects.

Histological analysis of failed cartilage repair after marrow stimulation for the treatment of large cartilage defect in medial compartmental osteoarthritis of the knee.

Bone marrow-stimulating techniques such as microfracture and subchondral drilling are valuable treatments for full-thickness cartilage defects. However, marrow stimulation-derived reparative tissues are not histologically well-documented in human osteoarthritis. We retrospectively investigated cartilage repairs after marrow stimulation for the treatment of large cartilage defects in osteoarthritic knees. Tissues were obtained from patients who underwent total knee arthroplasty (TKA) after arthroscopic marrow stimulation in medial compartmental osteoarthritis. Clinical findings and cartilage repair were assessed. Sections of medial femoral condyles were histologically investigated by safranin O staining and anti-type II collagen antibody. Marrow stimulation decreased the knee pain in the short term. However, varus leg alignment gradually progressed, and TKA conversions were required. The grade of cartilage repair was not improved. Marrow stimulations resulted in insufficient cartilage regeneration on medial femoral condyles. Safranin O-stained proteoglycans and type II collagen were observed in the deep zone of marrow-stimulated holes. This study demonstrated that marrow stimulation resulted in failed cartilage repair for the treatment of large cartilage defects in osteoarthritic knees. Our results suggest that arthroscopic marrow stimulation might not improve clinical symptoms for the long term in patients suffering large osteoarthritic cartilage defects.

Rekonstrukcja tkanki chrzęstnej biomateriałami polimerowymi – wczesne wyniki makroskopowe i histologiczne

Summary Introduction The surgical treatment of large cartilage defects in the region of head and neck is often impossible because of the atrophy of surrounding tissues and lack of suitable material for reconstruction. In the surgical treatment many of methods and reconstructive materials have been used. For many years the suitable synthetic material for the cartilage defects reconstruction has been searched for. The aim of the study was to evaluate two different biomaterials with proper mechanical and biological features for the cartilage replacement. Material and methods Two type of biomaterials in this study were used: resorbable polymer – poly(L-lactide-co-glycolide) (PLG) acting as a supportive matrix. A thin layer of sodium hyaluronate (Hyal) was also deposited on the surface as well in the pore walls of PLG scaffolds in order to provide biologically active molecules promoting differentiation and regeneration of the tissue. The studies were performed on the 50 animals – rabbits divided into 2 groups. The animals were operated in the general anaesthesia. The incision was done along the edge of the rabbit's auricle. Perichondrium and cartilage of the auricle on the surface 4 × 3 cm were prepared. Subperichondrically 1 × 1 cm fragment of the cartilage was removed by the scissors. This fragment was then replaced by the biomaterials: PLG in first group of 25 rabbits and PLG-Hyal in second group 25 rabbits. The tissues were sutured with polyglycolide Safil® 3–0. The animals obtained Enrofloxacin® for three days after the operation. Then 1, 4 and 12 weeks after the surgery the animals were painlessly euthanized by an overdose of Morbital®. Implants and surrounding tissues were excised and observed macroscopically and using an optical microscope. Results In all the observation periods we observed proper macroscopic healing process of biomaterials. We didn’t state strong inflammatory process and necrosis around the implanted biomaterials. Conclusions The histological and macroscopic examinations indicated that both materials developed in this study have properties similar to cartilaginous tissue and seem to be good for her restoration. Although the quickest tissue regeneration was found after implantation of PLG-Hyal.

New Technique for Cell-Seeded Collagen Matrix-Supported Autologous Chondrocyte Transplantation

Autologous chondrocyte transplantation/implantation (ACT/ACI) is becoming increasingly common for the treatment of large cartilage defects in the knee joint. The traditional ACT technique involves injection of a suspension of cells into the cartilage defect, which is covered with a periosteal flap or collagen membrane. The technique requires extensive suturing to create an effective seal; however, cell leakage remains a potential problem. Matrix-induced autologous chondrocyte implantation (MACI/MACT) avoids this potential problem by using a membrane on which chondrocytes are seeded and cultured for several days, before the membrane is cut to the correct size and shape of the defect. Time-consuming extensive suturing is unnecessary. However, cutting and repeated manipulation of the seeded membrane may result in the loss of critical chondrocytes. A modified technique termed ACT-collagen membrane seeding (ACT-Cs) has been developed in which expanded chondrocytes are applied to the collagen membrane after it has been cut to size, substantially reducing the risk of viable cell loss while retaining the ease and speed of the MACI/MACT procedure. In addition, the seeding of mitotically active chondrocytes onto the membrane after expansion and immediately before transplantation allows direct application of high cell concentrations.