Tom Minas

Two- to 9-year outcome after autologous chondrocyte transplantation of the knee.

Autologous cultured chondrocyte transplantation was introduced in Sweden in 1987 for the treatment of large (1.5-12.0 cm2) full thickness chondral defects of the knee. The clinical, arthroscopic, and histologic results from the first 101 patients treated using this technique are reported in this study. Patients were assessed retrospectively using three types of endpoints: patient and physician derived clinical rating scales (five validated and two new); arthroscopic assessment of cartilage fill, integration, and surface hardness; and standard histochemical techniques. Ninety-four patients with 2- to 9-years followup were evaluable. Good to excellent clinical results were seen in individual groups as follows: isolated femoral condyle (92%), multiple lesions (67%), osteochondritis dissecans (89%), patella (65%), and femoral condyle with anterior cruciate ligament repair (75%). Arthroscopic findings in 53 evaluated patients showed good repair tissue fill, good adherence to underlying bone, seamless integration with adjacent cartilage, and hardness close to that of the adjacent tissue. Hypertrophic response of the periosteum or graft or both was identified in 26 arthroscopies; seven were symptomatic and resolved after arthroscopic trimming. Graft failure occurred in seven (four of the first 23 and three of the next 78) patients. Histologic analysis of 37 biopsy specimens showed a correlation between hyalinelike tissue (hyaline matrix staining positive for Type II collagen and lacking a fibrous component) and good to excellent clinical results. The good clinical outcomes of autologous chondrocyte transplantation in this study are encouraging, and clinical trials are being done to assess the outcomes versus traditional fibrocartilage repair techniques.

Treatment of osteochondritis dissecans of the knee with autologous chondrocyte transplantation results at two to ten years

Background: Osteochondritis dissecans of the knee is a challenging clinical problem. We previously reported on the early successful results of autologous chondrocyte transplantation for the treatment of focal cartilage defects. The purpose of the present study was to assess the intermediate to long-term results of this technique in a large group of patients with osteochondritis dissecans.Methods: Fifty-eight patients with radiographically documented osteochondritis dissecans of the knee underwent treatment with autologous chondrocyte transplantation between 1987 and 2000 and were assessed clinically with use of standard rating scales. Twenty-two patients consented to arthroscopic second-look evaluation of graft integrity.Results: The mean age of the patients at the time of autologous chondrocyte transplantation was 26.4 years (range, fourteen to fifty-two years). Seven patients were less than eighteen years old. Thirty-five patients (60%) had juvenile-onset disease, and forty-eight patients (83%) had had a mean of 2.1 prior operations. The defect was located on the medial femoral condyle in thirty-nine patients and on the lateral femoral condyle in nineteen. The mean lesion size was 5.7 cm 2 (range, 1.5 to 12.0 cm 2 ), and the mean defect depth was 7.8 mm (range, 4 to 15 mm). After a mean duration of follow-up of 5.6 years, 91% of the patients had a good or excellent overall rating on the basis of a clinician evaluation and 93% had improvement on a patient self-assessment questionnaire. The Tegner-Wallgren, Lysholm, and Brittberg-Peterson VAS scores were all improved. The macroscopic quality of graft integrity averaged 11.2 on a 12-point scale, with only one graft having a score of <9 points. Two patients had a failure of treatment in the early postoperative period. Only one patient who had had a good or excellent rating at two years had a decline in clinical status at the time of the latest follow-up.Conclusions: Treatment of osteochondritis dissecans lesions of the knee with autologous chondrocyte transplantation produces an integrated repair tissue with a successful clinical result in >90% of patients. We recommend the wider use of autologous chondrocyte transplantation for this condition.

Current Concepts in the Treatment of Articular Cartilage Defects

Over time, articular cartilage loses the capacity to regenerate itself, making repair of articular surfaces difficult. Lavage and debridement may offer temporary relief of pain for up to 4.5 years, but offer no prospect of long-term cure. Likewise, marrow-stimulation techniques such as drilling, microfracture, or abrasion arthroplasty fail to yield long-term solutions because they typically promote the development of fibrocartilage. Fibrocartilage lacks the durability and many of the mechanical properties of the hyaline cartilage that normally covers articular surfaces. Repair tissue resembling hyaline cartilage can be induced to fill in articular defects by using perichondrial and periosteal grafts. However, these techniques are limited by the amount of tissue available for grafting and the tendency toward ossification of the repair tissue. Autogenous osteochondral arthroscopically implanted grafts (mosaicplasty), or open implantation of lateral patellar facet (Outerbridge technique), requires violation of subchondral bone. Osteochondral allografts risk viral transmission of disease and low chondrocyte viability, in addition to removal of host bone for implantation. Autologous chondrocyte implantation offers the opportunity to achieve biologic repair, enabling the surgeon to repair the joint surface with autologous articular cartilage. With this technique, care must be taken to ensure the safety, viability, and microbial integrity of the autologous cells while they are expanded in culture over a 4- to 5-week period prior to implantation. Surgical implantation requires equal attention to meticulous technique. In the future, physiologic repair also may become possible using mesenchymal stem cells or chondrocytes delivered surgically in an ex vivo-derived matrix. This would allow in vitro manipulation of cells with growth factors, mechanical stimuli, and matrix sizing to allow implantation of mature biosynthetic grafts which would allow treatment of larger defects with decreased rehabilitation and morbidity.

Effect of Cultured Autologous Chondrocytes on Repair of Chondral Defects in a Canine Model

Articular cartilage has a limited capacity for repair. In recent clinical and animal experiments, investigators have attempted to elicit the repair of defects of articular cartilage by injecting cultured autologous chondrocytes under a periosteal flap (a layer of periosteum). The objective of the present study was to determine the effect of cultured autologous chondrocytes on healing in an adult canine model with use of histomorphometric methods to assess the degree of repair. A total of forty-four four-millimeter-diameter circular defects were created down to the zone of calcified cartilage in the articular cartilage of the trochlear groove of the distal part of the femur in fourteen dogs. The morphology and characteristics of the original defects were defined in an additional six freshly created defects in three other dogs. Some residual non-calcified articular cartilage, occupying approximately 2 per cent of the total cross-sectional area of the defect, was sometimes left in the defect. The procedure sometimes damaged the calcified cartilage, resulting in occasional microfractures or larger fractures, thinning of the zone of calcified cartilage, or, rarely, small localized penetrations into subchondral bone. The forty-four defects were divided into three treatment groups. In one group, cultured autologous chondrocytes were implanted under a periosteal flap. In the second group, the defect was covered with a periosteal flap but no autologous chondrocytes were implanted. In the third group (the control group), the defects were left empty. The defects were analyzed after twelve or eighteen months of healing. Histomorphometric measurements were made of the percentage of the total area of the defect that became filled with repair tissue, the types of tissue that filled the defect, and the integration of the repair tissue with the adjacent cartilage at the sides of the defects and with the calcified cartilage at the base of the defect. In histological sections made through the center of the defects in the three groups, the area of the defect that filled with new repair tissue ranged from a mean total value of 36 to 76 per cent, with 10 to 23 per cent of the total area consisting of hyaline cartilage. Integration of the repair tissue with the adjacent cartilage at the edges of the defect ranged from 16 to 32 per cent in the three groups. Bonding between the repair tissue and the calcified cartilage at the base of the defect ranged from 41 to 89 per cent. With the numbers available, we could detect no significant difference among the three groups with regard to any of the parameters used to assess the quality of the repair. In the two groups in which a periosteal flap was sutured to the articular cartilage surrounding the defect, the articular cartilage showed degenerative changes that appeared to be related to that suturing. CLINICAL RELEVANCE: The technique of injecting cultured autologous chondrocytes under a periosteal flap recently was introduced to treat defects in the articular cartilage of humans. The long-term efficacy of this treatment is unknown. An animal model was developed to evaluate the procedure and its effectiveness.

Articular Cartilage Lesions of the Knee

From *Santa Monica Orthopaedic and Sports Medicine Group, Santa Monica, California; ‡University of Missouri at Kansas City and University of Kansas, Shawnee Mission, Kansas; §Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania; iDivision of Sports Medicine, Children’s Hospital, Boston, Massachusetts; Baylor Sports Medicine Group, Houston, Texas; Orthopaedische Universitaetsklinik, Freiburg, Germany; Brigham Orthopedic Association, Boston, Massachusetts; and Gothenburg Medical Center, Vastra Frolunda, Sweden

Histologic analysis of tissue after failed cartilage repair procedures.

This study evaluated the composition of reparative tissue retrieved during revision surgery from full thickness chondral defects in 18 patients in whom abrasion arthroplasty (n = 12), grafting of perichondrial flaps (n = 4), and periosteal patching augmented by autologous chondrocyte implantation in cell suspension (n = 6) failed to provide lasting relief of symptoms. The defects were graded by gross appearance, and all of the tissue filling the defect was retrieved. Histologic evaluation included histomorphometric analysis of the percentage of selected tissue types in cross sections. Immunohistochemistry was performed using antibodies to Types I, II, and X collagen. The histologic appearance of material retrieved after abrasion arthroplasty was that of fibrous, spongiform tissue comprising Type I collagen in 22% +/- 9% (mean +/- standard error of the mean) of the cross sectional area, and degenerating hyaline tissue (30% +/- 10%) and fibrocartilage (28% +/- 7%) with positive Type II collagen staining. Three of four specimens obtained after implantation of perichondrium failed as a result of bone formation that was found in 19% +/- 6% of the cross sectional area, including areas staining positive for Type X collagen, as an indicator for hypertrophic chondrocytes. Revision after autologous chondrocyte implantation was associated with partial displacement of the periosteal graft from the defect site because of insufficient ongrowth or early suture failure. When the graft edge displaced, repair tissue was fibrous (55% +/- 11%), whereas graft tissue attached to subchondral bone displayed hyaline tissue (to 6%) and fibrocartilage (to 12%) comprising Type II collagen at 3 months after surgery. Evaluation of retrieved repair tissue after selected cartilage repair procedures revealed distinctive histologic features reflecting the mechanisms of failure.

Autologous chondrocyte implantation for focal chondral defects of the knee.

Autologous chondrocyte implantation has been used since March 1995 in a prospective cohort evaluation. One hundred sixty-nine patients, 13 to 58 years, have been treated as of December 1999. One hundred seven patients have greater than 12 months followup, and 56 have greater than 24 months followup. Overall 87% of patients improved. Patient assessment instruments include the modified Cincinnati knee rating scale, Short Form-36, Knee Society score, Western Ontario McMaster Universities Osteoarthritis Index score, and patient satisfaction survey. Treatment cases included the following categories: Simple (N = 12) isolated femoral condyles; Complex (N = 86) nonarthritic knees with multiple defects on the femur, or isolated lesions to the patella or tibia; and Salvage (N = 71) knees with early arthritic changes. The areas treated were large: Simple, 4.3 cm 2 (one defect); Complex, 6.75 cm 2 (4.5 cm 2 per defect × 1.5 defects per case), and Salvage, 11.66 cm 2 (5.3 cm 2 per defect × 2.2 defects per case). Patients who had complex and salvage treatments (N = 107) with greater than 1 year followup frequently had adjuvant treatments including valgus tibial (N = 24) or tibial tubercle (N = 15) osteotomies or ligament reconstruction (N = 5). At the 2-year followup, statistically significant functional improvements occurred in the patients in the Simple and Complex categories (Cincinnati score; Simple, baseline 3.57, 24 months = 5.38; Complex, baseline 3.40, 24 months = 6.06;). Patients in the Salvage category had statistically significant improvement in Short Form-36 quality of life scores (Physical summary, 24 months) and an increase in the Cincinnati rating scale when the patellofemoral joint was not involved. Patient satisfaction at 24 months for Simple, Complex, and Salvage categories was 60%, 70%, and 90%, respectively. There were 22 failures in 169 patients treated (13%), which was defined as no clinical improvement or graft failure.

Canine chondrocytes seeded in type I and type II collagen implants investigated In Vitro

Synthetic and natural absorbable polymers have been used as vehicles for implantation of cells into cartilage defects to promote regeneration of the articular joint surface. Implants should provide a pore structure that allows cell adhesion and growth, and not provoke inflammation or toxicity when implanted in vivo. The scaffold should be absorbable and the degradation should match the rate of tissue regeneration. To facilitate cartilage repair the chemical structure and pore architecture of the matrix should allow the seeded cells to maintain the chondrocytic phenotype, characterized by synthesis of cartilage-specific proteins. We investigated the behavior of canine chondrocytes in two spongelike matrices in vitro: a collagen-glycosaminoglycan (GAG) copolymer produced from bovine hide consisting of type I collagen and a porous scaffold made of type II collagen by extraction of porcine cartilage. Canine chondrocytes were seeded on both types of matrices and cultured for 3 h, 7 days, and 14 days. The histology of chondrocyte-seeded implants showed a significantly higher percentage of cells with spherical morphology, consistent with chondrocytic morphology, in the type II sponge at each time point. Pericellular matrix stained for proteoglycans and for type II collagen after 14 days. Biochemical analysis of the cell seeded sponges for GAG and DNA content showed increases with time. At day 14 there was a significantly higher amount of DNA and GAG in the type II matrix. This is the first study that directly compares the behavior of chondrocytes in type I and type II collagen matrices. The type II matrix may be of value as a vehicle for chondrocyte implantation on the basis of the higher percentage of chondrocytes retaining spherical morphology and greater biosynthetic activity that was reflected in the greater increase of GAG content.

ADVANCED TECHNIQUES IN AUTOLOGOUS CHONDROCYTE TRANSPLANTATION

Autologous chondrocyte transplantation (ACT) provides durable hyaline repair tissue in correctly selected patients; it is indicated for full thickness, weightbearing condyle injuries, and injuries to the trochlea of the femur. ACT results in reproducibly satisfactory results, with return to high level activities, including sports, in over 90% of these patients. Second look arthroscopies demonstrate macroscopic integrity of the grafts; and biopsies demonstrate hyaline cartilage repair, which is critical, as shown clinically, to giving durable results at two to nine years follow-up. Also discussed in this article is surgical technique which is especially important for complex reconstructions. As technical refinements and rehabilitation protocols improve, results for treating patellar and tibial injuries may improve; at this time, the response to treating bipolar focal chondral injuries is unknown and not recommended.

Increased Failure Rate of Autologous Chondrocyte Implantation After Previous Treatment With Marrow Stimulation Techniques

Background Marrow stimulation techniques such as drilling or microfracture are first-line treatment options for symptomatic cartilage defects. Common knowledge holds that these treatments do not compromise subsequent cartilage repair procedures with autologous chondrocyte implantation. Hypothesis Cartilage defects pretreated with marrow stimulation techniques will have an increased failure rate. Study Design Cohort study; Level of evidence, 2. Methods The first 321 consecutive patients treated at one institution with autologous chondrocyte implantation for full-thickness cartilage defects that reached more than 2 years of follow-up were evaluated by prospectively collected data. Patients were grouped based on whether they had undergone prior treatment with a marrow stimulation technique. Outcomes were classified as complete failure if more than 25% of a grafted defect area had to be removed in later procedures because of persistent symptoms. Results There were 522 defects in 321 patients (325 joints) treated with autologous chondrocyte implantation. On average, there were 1.7 lesions per patient. Of these joints, 111 had previously undergone surgery that penetrated the subchondral bone; 214 joints had no prior treatment that affected the subchondral bone and served as controls. Within the marrow stimulation group, there were 29 (26%) failures, compared with 17 (8%) failures in the control group. Conclusion Defects that had prior treatment affecting the subchondral bone failed at a rate 3 times that of nontreated defects. The failure rates for drilling (28%), abrasion arthroplasty (27%), and microfracture (20%) were not significantly different, possibly because of the lower number of microfracture patients in this cohort (25 of 110 marrow-stimulation procedures). The data demonstrate that marrow stimulation techniques have a strong negative effect on subsequent cartilage repair with autologous chondrocyte implantation and therefore should be used judiciously in larger cartilage defects that could require future treatment with autologous chondrocyte implantation.