[Show abstract][Hide abstract] ABSTRACT: Background: There is a need for tools to predict the chondrogenic potency of autologous cells for cartilage repair.
Purpose: To evaluate previously proposed chondrogenic biomarkers and to identify new biomarkers in the chondrocyte transcriptome
capable of predicting clinical success or failure after autologous chondrocyte implantation.
Study Design: Controlled laboratory study and case-control study; Level of evidence, 3.
Methods: Five patients with clinical improvement after autologous chondrocyte implantation and 5 patients with graft failures
3 years after implantation were included. Surplus chondrocytes from the transplantation were frozen for each patient. Each
chondrocyte sample was subsequently thawed at the same time point and cultured for 1 cell doubling, prior to RNA purification and
global microarray analysis. The expression profiles of a set of predefined marker genes (ie, collagen type II a1 [COL2A1], bone
morphogenic protein 2 [BMP2], fibroblast growth factor receptor 3 [FGFR3], aggrecan [ACAN], CD44, and activin receptor–like
kinase receptor 1 [ACVRL1]) were also evaluated.
Results: No significant difference in expression of the predefined marker set was observed between the success and failure
groups. Thirty-nine genes were found to be induced, and 38 genes were found to be repressed between the 2 groups prior to
autologous chondrocyte implantation, which have implications for cell-regulating pathways (eg, apoptosis, interleukin signaling,
and b-catenin regulation).
Conclusion: No expressional differences that predict clinical outcome could be found in the present study, which may have
implications for quality control assessments of autologous chondrocyte implantation. The subtle difference in gene expression
regulation found between the 2 groups may strengthen the basis for further research, aiming at reliable biomarkers and quality
control for tissue engineering in cartilage repair.
Clinical Relevance: The present study shows the possible limitations of using gene expression before transplantation to predict
the chondrogenic and thus clinical potency of the cells. This result is especially important as the chondrogenic potential of the
chondrocytes is currently part of quality control measures according to European and American legislations regarding advanced
The Orthopaedic Journal of Sports Medicine. 09/2014;
[Show abstract][Hide abstract] ABSTRACT: Background: Autologous chondrocyte implantation (ACI) continues to technically evolve, but how the technical innovations affect the ability to participate in high-impact sports such as football is unknown. Methods: Clinical studies describing athletes treated with first-, second-, or third-generation ACI techniques were reviewed. The technical developments of ACI were evaluated, and the results in athletes and specifically football (soccer) players were analyzed. Results: Football players reported 72% good to excellent results with significant overall improvement of knee function and activity scores. Return to football was 83% in competitive players but lower in recreational players. Eighty percent of players returned to the same competitive level after ACI, and 87% to 100% maintained their ability to play sports at 5 years postoperatively. Return to sport was better for younger, competitive players with shorter intervals between injury and ACI. New developments of the surgical technique and postoperative rehabilitation were able to reduce the limitations associated with first-generation ACI including invasiveness, graft hypertrophy, and particularly long postoperative rehabilitation. This allowed for faster return to sports like football without compromising the ability for continued competition over time. Conclusion: Articular cartilage repair in football players often allows for successful return to this high-impact sport with excellent durability. The continued evolution of this technique has improved initial shortcomings with important implications for both the professional and recreational athlete.
[Show abstract][Hide abstract] ABSTRACT: The aim of our current study is to present the 12.6 years' follow-up results in patients with cartilage lesions of the patellofemoral joint, treated with autologous chondrocyte implantation (ACI) with the use of periosteum.
Ninety-two patients having patella or trochlea lesion participated in this study. Lysholm and Tegner questionnaires were completed 12.6 years (SD 2.3 years) after the surgery. The patients were asked whether they feel better, worse or had not experienced any difference compared to previous years and whether they would undergo the operation again. Complications or subsequent surgeries were also assessed.
Median Tegner score was three, improved by one level compared with preoperative values (P = 0.02). Median Lysholm score was 70, improved by nine points (n.s.). Seventy-two percent of the patients were better or unchanged while 93% would undergo the operation again. Patients with no kissing lesions appeared to have a better prognosis. Patients with malalignment or instability that had undergone a realignment procedure had comparable outcomes to the patients that did not need any additional surgery. Realignment procedures increased the incidence of serious complications but they were associated with decreased incidence of periosteal hypertrophy. No association was found between the age of the patients at the time of the ACI or the size per lesion and any of the clinical outcomes.
ACI provides a satisfactory outcome for the treatment of cartilage lesions of the patellofemoral joint, even for the cases with concomitant patellar instability. It seems that correcting the coexisting background factors with realignment, stabilizing or unloading procedures, along with the treatment of cartilage lesions, is improving the clinical outcomes over time and decreases the incidence of periosteal hypertrophies although increasing the incidence of serious complications. Our study reveals the good results and the high level of patients' activities (as shown by Tegner score), were preserved 12.6 years after the implantation, in both isolated trochlea and patella lesions and also in multiple and in kissing lesions where an intervention could be considered as a salvage procedure.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: The purpose of this study is to evaluate the overall improvement of autologous chondrocyte implantation (ACI) treated patients at medium and long-term follow-up in terms of clinical assessment and patient's satisfaction. We also aimed to identify possible factors associated with improvement in clinical outcomes and with better or worse functionality and patients' satisfaction. DESIGN: We evaluated 224 patients treated with ACI with periosteum. Lysholm, Tegner-Wallgren and Brittberg scores were assessed pre-operatively, at 3.1 years on average (range 1-8.3) and at 12.8 on average (range 10-20 years) after the surgery. The patients were also asked to grade their satisfaction regarding the current knee function compared with intermediate results and to report whether they would do the operation again. RESULTS: ACI is associated with substantial improvement in all the clinical outcomes, even 10-20 years after the implantation, although a small deterioration was noticed between intermediate and final evaluations. Seventy-three percent of the patients report to be improved or the same compared to previous follow-up, while 93% would do the operation again. CONCLUSIONS: ACI improves the clinical status of operated patients, retaining the benefit over time. Concomitant injuries like meniscal lesions or anterior cruciate ligament deficiencies, if treated, do not seem to alter the effectiveness of the ACI.
Osteoarthritis and Cartilage 05/2010; · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The medium-term results of autologous chondrocyte implantation (ACI) have shown good to excellent outcomes for the majority of patients. However, no long-term results 10 to 20 years after the surgery have been reported.
Autologous chondrocyte implantation provides a durable solution to the treatment of full-thickness cartilage lesions of the knee, maintaining good clinical results even 10 to 20 years after implantation.
Case series; Level of evidence, 4.
In this uncontrolled study, questionnaires with the Lysholm, Tegner-Wallgren, Brittberg-Peterson, modified Cincinnati (Noyes), and Knee Injury and Osteoarthritis Outcome Score (KOOS) scores were sent to 341 patients. Preoperative Lysholm, Tegner-Wallgren, and Brittberg-Peterson scores were also retrieved when possible from patients' files. The patients were asked to grade their status during the past 10 years as better, worse, or unchanged. Finally, they were asked if they would do the operation again.
There were 224 of 341 patients who replied to our posted questionnaires and were assessed. The mean cartilage lesion size was 5.3 cm(2). Ten to 20 years after the implantation (mean, 12.8 years), 74% of the patients reported their status as better or the same as the previous years. There were 92% who were satisfied and would have the ACI again. The Lysholm, Tegner-Wallgren, and Brittberg-Peterson scores were improved compared with the preoperative values. The average Lysholm score improved from 60.3 preoperatively to 69.5 postoperatively, the Tegner from 7.2 to 8.2, and the Brittberg-Peterson from 59.4 to 40.9. At the final measurement, the KOOS score was on average 74.8 for pain, 63 for symptoms, 81 for activities of daily living (ADL), 41.5 for sports, and 49.3 for quality of life (QOL). The average Noyes score was 5.4. Patients with bipolar lesions had a worse final outcome than patients with multiple unipolar lesions. The presence of meniscal injuries before ACI or history of bone marrow procedures before the implantation did not appear to affect the final outcomes. The age at the time of the operation or the size of lesion did not seem to correlate with the final outcome.
Autologous chondrocyte implantation has emerged as an effective and durable solution for the treatment of large full-thickness cartilage and osteochondral lesions of the knee joint. Our study suggests that the clinical and functional outcomes remain high even 10 to 20 years after the implantation.
The American Journal of Sports Medicine 02/2010; 38(6):1117-24. · 4.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Various treatment options are available for articular cartilage lesions, but controversy exists regarding the quality of the repair tissue and the durability of the results posttreatment. Noninvasive techniques are needed for the assessment of the repair tissue.
Magnetic resonance imaging (MRI) with delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) can give valuable information regarding the quality and quantity of the repaired cartilage lesion.
Cohort study; Level of evidence, 3.
Thirty-six knees in 31 patients were assessed 9 to 18 years after treatment with autologous chondrocyte implantation (ACI). All patients had isolated lesions. The knees were clinically evaluated with the Knee injury and Osteoarthritis Outcome Score and the dGEMRIC technique. The T1 value was measured for 2 regions of interest (ROIs), 1 in the repair tissue area (ROI 1) and 1 in the surrounding cartilage (ROI 2), giving information of the content of proteoglycans.
The average T1 value in ROI 1 was 467.5 milliseconds and in ROI 2, 495.3 milliseconds, which yielded no significant difference, thus suggesting comparable levels of proteoglycans in the repair tissue and surrounding cartilage. Intralesional osteophytes were in 64% of the lesions, mainly in younger patients with osteochondritis dissecans lesions or a history of subchondral bone surgeries. Medium or large bone marrow edema was found in 14% of the knees and subchondral cysts, in 39%. There was no correlation between the KOOS and any MRI findings.
Magnetic resonance imaging with dGEMRIC gives valuable information for the macroscopic appearance and micro-molecular quality of the repair tissue after ACI. Nine to 18 years posttreatment, the quality of the repair tissue is similar to the surrounding normal cartilage, although intralesional osteophytes, subchondral cysts, and bone marrow edema were common. The defect area is restored in most patients. However, there was no correlation between the dGEMRIC values and the KOOS outcomes.
The American Journal of Sports Medicine 02/2010; 38(5):943-9. · 4.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Local attempts to repair a cartilage lesion could cause increased levels of anabolic and catabolic factors in the synovial fluid. After repair with regenerated cartilage, the homeostasis of the cartilage ideally would return to normal. In this pilot study, we first hypothesized levels of synovial fluid markers would be higher in patients with cartilage lesions than in patients with no cartilage lesions, and then we hypothesized the levels of synovial fluid markers would decrease after cartilage repair. We collected synovial fluid samples from 10 patients before autologous chondrocyte transplantation of the knee. One year later, a second set of samples was collected and arthroscopic evaluation of the repair site was performed. Fifteen patients undergoing knee arthroscopy for various symptoms but with no apparent cartilage lesions served as control subjects. We measured synovial fluid matrix metalloproteinase-3 (MMP-3) and insulinlike growth factor-I (IGF-I) concentrations with specific activity and enzyme-linked immunosorbent assays, respectively. The levels of MMP-3 and IGF-I were higher in patients having cartilage lesions than in control subjects with no cartilage lesions. One year after cartilage repair, the lesions were filled with repair tissue, but the levels of MMP-3 and IGF-I remained elevated, indicating either graft remodeling or early degeneration. Level of Evidence: Level III, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
Clinical Orthopaedics and Related Research 09/2008; 467(1):267-72. · 2.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Articular cartilage injuries cause a major clinical problem because of the negligible repair capacity of cartilage. Autologous chondrocyte transplantation is a surgical method developed to repair cartilage lesions. In the operation, cartilage defect is covered with a periosteal patch and the suspension of cultured autologous chondrocytes is injected into the lesion site. The method can form good repair tissue, but new techniques are needed to make the operation easier and to increase the postoperative biomechanical properties of the repair tissue. In this study, we investigated poly-L,D-lactic acid (PLDLA) scaffolds alone or seeded with autologous chondrocytes in the repair of circular 6-mm cartilage lesions in immature porcine knee joints. Spontaneous repair was used as a reference. Histologic evaluation of the repair tissue showed that spontaneous repair exhibited higher scores than either PLDLA scaffold group (with or without seeded chondrocytes). The scaffold material was most often seen embedded in the subchondral bone underneath the defect area, probably because of the hardness of the PLDLA material. However, some of the cell-seeded and nonseeded scaffolds contained cartilaginous tissue, suggesting that invasion of mesenchymal cells inside nonseeded scaffolds had occurred. Hyaluronan deposited in the scaffold had possibly acted as a chemoattractant for the cell recruitment. In conclusion, the PLDLA scaffold material used in this study was obviously mechanically too hard to be used for cartilage repair in immature animals.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to find out how deep chondral lesions heal in growing animals spontaneously and after autologous chondrocyte transplantation.
A 6mm deep chondral lesion was created in the knee joints of 57 immature pigs and repaired with autologous chondrocyte transplantation covered with periosteum or muscle fascia, with periosteum only, or left untreated. After 3 and 12 months, the repair tissue was evaluated with International Cartilage Repair Society (ICRS) macroscopic grading, modified O'Driscoll histological scoring, and staining for collagen type II and hyaluronan, and with toluidine blue and safranin-O staining for glycosaminoglycans. The repair tissue structure was also examined with quantitative polarized light microscopy and indentation analysis of the cartilage stiffness.
The ICRS grading indicated nearly normal repair tissue in 65% (10/17) after the autologous chondrocyte transplantation and 86% (7/8) after no repair at 3 months. At 1 year, the repair tissue was nearly normal in all cases in the spontaneous repair group and in 38% (3/8) in the chondrocyte transplantation group. In most cases, the cartilage repair tissue stained intensely for glycosaminoglycans and collagen type II indicating repair tissue with true constituents of articular cartilage. There was a statistical difference in the total histological scores at 3 months (P=0.028) with the best repair in the spontaneous repair group. A marked subchondral bone reaction, staining with toluidine blue and collagen type II, was seen in 65% of all animals.
The spontaneous repair ability of full thickness cartilage defects of immature pigs is significant and periosteum or autologous chondrocytes do not bring any additional benefits to the repair.
Osteoarthritis and Cartilage 11/2006; 14(10):1066-74. · 4.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Articular cartilage has no or very low ability of self-repair, and untreated lesions may lead to the development of osteoarthritis. One method which has been proven to result in long-term repair of isolated lesions is autologous chondrocyte transplantation. In this method, culture-expanded chondrocytes isolated from full-thickness biopsies, taken from a non-weight-bearing area at the supromedial edge of the femoral condyle, are transplanted back to the patient under a cover of periosteum. The treatment is able to regenerate hyaline cartilage with long-term durability. Although the repair mechanism behind this treatment has not been fully elucidated, emerging data generated by microarray technologies reveal an interesting regeneration process involving cellular and molecular mechanisms found during fetal development. In hyaline cartilage, the human chondrocyte population is generally considered a homogenous cell population, but recently several investigators have demonstrated that cells isolated from human articular cartilage have stem cell properties and that the superficial layer contains such cells. This paper will discuss these recent data and their implications for future treatment strategies aiming to induce regeneration in articular cartilage surfaces.
[Show abstract][Hide abstract] ABSTRACT: The ability of autologous chondrocyte transplantation to produce and maintain an effective articular cartilage repair under high mechanical demands has not been investigated.
Autologous chondrocyte transplantation provides a reliable and durable repair of full-thickness knee articular cartilage lesions in high-demand athletes.
Case series; Level of evidence, 4.
A total of 45 soccer players were evaluated 41 +/- 4 months after autologous chondrocyte transplantation for their ability to return to soccer, the timing of their return, skill level, and functional outcome rating by the Tegner activity rating scale score and Brittberg score. The factors influencing the return to sport were analyzed.
Of these players, 72% reported good to excellent results, with significant overall improvement of Tegner activity rating scale scores; 33% returned to soccer, including 83% of competitive-level players and 16% of recreational players. Of the returning players, 80% returned to the same skill level and 87% maintained their ability to play soccer at 52 +/- 8 months postoperatively. Players who successfully returned to soccer were significantly younger and had a shorter preoperative duration of symptoms than did patients who did not return to the sport. Concomitant adjuvant procedures did not adversely affect the ability to return to soccer.
Repair of knee articular cartilage lesions by autologous chondrocyte transplantation in high-performance athletes is particularly successful in younger, competitive athletes with limited preoperative intervals.
The American Journal of Sports Medicine 12/2005; 33(11):1639-46. · 4.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Limited information exists about the treatment of full-thickness articular cartilage lesions of the knee in adolescent athletes.
To evaluate the functional outcome and athletic activity after articular cartilage repair in the knees of adolescent athletes.
Case series; Level of evidence, 4.
Twenty adolescent athletes with full-thickness articular cartilage lesions of the knee were treated with autologous chondrocyte transplantation. Functional outcome was evaluated by subjective patient outcome rating, knee activity scores, and level of athletic participation.
At a mean of 47 months after autologous chondrocyte transplantation, 96% of adolescents reported good or excellent results with significant increases in postoperative Tegner activity scores and Lysholm scores. Ninety-six percent returned to high-impact sports and 60% to an athletic level equal or higher than that before knee injury. Return to preinjury sports correlated with shorter preoperative symptoms and a lower number of prior operations. All adolescents with preoperative symptoms < or =12 months returned to preinjury-level athletics, compared to 33% with preoperative intervals longer than 12 months.
Treatment of full-thickness articular injuries of the knee in adolescent athletes with autologous chondrocyte transplantation yields a high rate of functional success at a mean follow-up of 47 months. The rate of return to demanding athletic activities is higher in cases in which the preoperative duration of symptoms is 12 months or less.
The American Journal of Sports Medicine 09/2005; 33(8):1147-53. · 4.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our main hypothesis was that indentation stiffness of the repair tissue approaches the values of adjacent cartilage 1 year after autologous chondrocyte transplantation. We also wanted to investigate the differences between osteochondritic lesions and full-thickness lesions. Thirty patients with cartilage lesions were operated on with autologous chondrocyte transplantation. The repair was evaluated arthroscopically, indentation stiffness was measured, and clinical evaluations were done. The stiffness of the repair tissue improved to 62% (mean 2.04 +/- 0.83 N, mean +/- SD) of adjacent cartilage (3.58 +/- 1.04 N). Fifty-three percent of the patients graded their knee as excellent or good and 47% of the patients graded their knee as fair at the followup. In six patients the normalized stiffness was at least 80%, suggesting hyaline-like repair. The indentation stiffness of the osteochondritis dissecans lesion repairs (1.45 +/- 0.46 N; n = 7) was less than that of the nonosteochondritis dissecans lesion repair sites (2.37 +/- 0.72 N; n = 19). Gadolinium-enhanced magnetic resonance imaging of the cartilage (dGEMRIC) during followup of four patients suggested proteoglycan replenishment, although all grafts showed low indentation values. Low stiffness values may indicate incomplete maturation or predominantly fibrous repair. The indentation analysis showed that the repair tissue stiffness could, in some cases, reach the same level as the adjacent cartilage, but there was a large variation among the grafts.
Clinical Orthopaedics and Related Research 05/2005; · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The anterior cruciate ligament-deficient knee is prone to osteoarthritis and meniscus lesions. Very little, however, is known about the biomechanical properties of articular cartilage in anterior cruciate ligament-deficient knees.
To evaluate biomechanical and macroscopical cartilage changes in the knee joint with respect to the time after anterior cruciate ligament rupture.
Chronic anterior cruciate ligament deficiency induces cartilage softening.
Cross-sectional study; Level of evidence, 3.
Cartilage stiffness of 50 patients undergoing anterior cruciate ligament reconstructive surgery because of symptomatic knee instability after chronic anterior cruciate ligament rupture was measured with an arthroscopic indenter device, and the number and size of cartilage lesions were evaluated.
The cartilage stiffness did not correlate with time from trauma to surgery (r = 0.002, P = .99), but the number of cartilage lesions in the knee increased when the time from the initial trauma to reconstructive surgery increased (r = 0.356, P = .011). Indentation values measured on healthy-looking cartilage on damaged joint surfaces were lower than the values measured on healthy joint surfaces (P < .01 on lateral femoral condyle and on tibial plateaus).
The number of cartilage lesions increases with increased time after initial trauma. The arthroscopic indenter device is able to detect cartilage softening as the early mechanical sign of degradation not yet visible to the eye.
The American Journal of Sports Medicine 03/2005; 33(3):408-14. · 4.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autologous chondrocyte transplantation (ACT) has been shown, in long-term follow-up studies, to be a promising treatment for the repair of isolated cartilage lesions. The method is based on an implantation of in vitro expanded chondrocytes originating from a small cartilage biopsy harvested from a non-weight-bearing area within the joint. In patients with osteoarthritis (OA), there is a need for the resurfacing of large areas, which could potentially be made by using a scaffold in combination with culture-expanded cells. As a first step towards a cell-based therapy for OA, we therefore investigated the expansion and redifferentiation potential in vitro of chondrocytes isolated from patients undergoing total knee replacement. The results demonstrate that OA chondrocytes have a good proliferation potential and are able to redifferentiate in a three-dimensional pellet model. During the redifferentiation, the OA cells expressed increasing amounts of DNA and proteoglycans, and at day 14 the cells from all donors contained type II collagen-rich matrix. The accumulation of proteoglycans was in comparable amounts to those from ACT donors, whereas total collagen was significantly lower in all of the redifferentiated OA chondrocytes. When the OA chondrocytes were loaded into a scaffold based on hyaluronic acid, they bound to the scaffold and produced cartilage-specific matrix proteins. Thus, autologous chondrocytes are a potential source for the biological treatment of OA patients but the limited collagen synthesis of the OA chondrocytes needs to be further explained.
Arthritis research & therapy 02/2005; 7(3):R560-8. · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clinical cartilage repair with transplantation of cultured chondrocytes, the first described technique introduced in 1994, includes a periosteal membrane but today cells are also implanted without the periosteal combination. The aim of this study was to see if the periosteum had more than a biomechanical function and if the periosteum had a biological effect on the seeded cells tested in an agarose system in which the clonal growth in agarose and the external growth stimulation could be analysed.
Four different experiments were used to study the growth of human chondrocytes in agarose and the periosteal influence. Human chondrocytes were isolated and transferred to either primary or secondary agarose culture. After 4 weeks, the total number of clones >50 microm was counted. Cocultures of chondrocytes and periosteal tissue, cultures of chondrocytes with conditioned medium from chondrocytes, periosteal cells and fibroblast were used to study a potential stimulatory effect on growth and different cytokines and growth factors were analysed.
It was found that the human chondrocytes had different growth properties in agarose with the formation of four different types of clones: a homogenous clone without matrix production, a homogenous clone with matrix production, a differentiated clone with matrix production and finally a differentiated clone without matrix production. The periosteum exerted a paracrine effect on cultured chondrocytes in agarose resulting in a higher degree of cloning. The chondrocytes produced significant amounts of interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor (TGF)-beta. The periosteum produced significant amounts of IL-6, IL-8 and TGF-beta. Cocultures of chondrocytes and periosteum demonstrated a potentiation of IL-6 and IL-8 release but not of TGF-beta and GM-CSF.
Articular chondrocytes are able to form clones of different properties in agarose and the periosteum has a capacity of stimulating chondrocyte clonal growth and differentiation and secretes significant amounts of IL-6, IL-8, GM-CSF and TGF-beta. It may be that the repair of cartilage defects with seeded chondrocytes could benefit from the combination with a periosteal graft. The production of TGF-beta by implanted chondrocytes could influence the chondrogenic cells in the periosteum to start a periosteal chondrogenesis and together with the matrix from implanted chondrocyte production, a repair of cartilaginous appearance may develop; a dual chondrogenic response is possible.
Osteoarthritis and Cartilage 02/2005; 13(2):146-53. · 4.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Repair of cartilage damage with autologous chondrocyte transplantation (ACT) has become popular in clinical use during the past few years. Although clinical results have mostly been successful, several unanswered questions remain regarding the biological mechanism of the repair process. The aim of this study was to develop a goat model for ACT. The repair was not successful due to the graft delamination, but we characterize the subchondral changes seen after the procedure. A chondral lesion was created in 14 goat knees, operated on 1 month later with ACT, and covered with periosteum or a bioabsorbable poly-L/D-lactide scaffold. After 3 months, only two of the five lesions repaired with ACT showed partly hyaline-like repair tissue, and all lesions (n = 4) with the scaffold failed. Even though the lesions did not extend through the calcified cartilage, the bone volume and collagen organization of bone structure were decreased when assessed by quantitative polarized light microscopy. There was a significant loss of bone matrix and distortion of the trabecular structure of subchondral bone, which extended several millimeters into the bone. The subchondral bone demonstrated strong hyaluronan staining in the bone marrow and cartilaginous areas with signs of endochondral ossification, suggesting structural remodeling of the bone. The goat model used here proved not to be an optimal model for ACT. The changes in subchondral bone may alter the biomechanical properties of the subchondral plate and thus the long-term survival of the repair tissue after ACT.
Calcified Tissue International 02/2004; 74(1):107-14. · 2.75 Impact Factor