Tim Bryant

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.

The role of autologous chondrocyte implantation in the patellofemoral joint.

In a prospective study to determine the clinical effectiveness of autologous chondrocyte implantation, 45 patients reached a minimum followup of 2 years (range, 2-7 years; average, 46.4 months) after treatment involving the patellofemoral articulation. There were 28 men (61%) and 17 women (39%) and the average age of the patients was 37.5 years (range, 15-55 years). The treatment groups included (I) isolated patella, n = 8; (II) isolated trochlea, n = 9; (III) patella plus trochlea, n = 4; (IV) weightbearing condyle plus patella n = 2; (V) weightbearing condyle plus trochlea, n = 2; and (VI) weightbearing condyle plus patella plus trochlea n = 20. The average surface area per patella (n = 34) was 4.86 cm2 and per trochlea (n = 34) it was 5.22 cm2. The average resurfacing per knee (n = 45) was 10.45 cm2. We showed a postoperative improvement in quality of life as measured by the Short Form-36; Western Ontario and McMaster University Score, Knee Society Score, modified Cincinnati Score, and a patient satisfaction survey. There were eight failures (18%) as a result of a patella or trochlea failure. Seventy-one percent of patients rated their outcomes as good or excellent, 22% rated outcome as fair, and 7% rated outcome as poor. Level of Evidence: Therapeutic Study, Level II-1 (prospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.

Repair of Large Chondral Defects of the Knee with Autologous Chondrocyte Implantation in Patients 45 Years or Older

Background Autologous chondrocyte implantation (ACI) has become an accepted option for the treatment of chondral defects in carefully selected patients. Current recommendations limit this procedure to younger patients, as insufficient data are available to conclusively evaluate outcomes in patients older than 45 years. Hypothesis Cartilage repair with ACI in patients older than 45 years results in substantially different outcomes than those previously reported for younger age groups. Study Design Case series; Level of evidence, 4. Methods This prospective cohort study reviewed patients 45 years of age at the time of treatment with ACI. The clinical evaluation included a patient satisfaction questionnaire and four validated rating scales: Short Form-36, Modified Cincinnati Rating Scale, WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index, and the Knee Society Score. Results A total of 56 patients 45 years of age were treated with ACI. The average patient age at index surgery was 48.6 years (range, 45–60 years). The minimum follow-up was 2 years (range, 2–11 years; mean, 4.7 years). The cohort included 36 men and 20 women. The mean transplant size was 4.7 cm2 per defect (range, 1–15.0 cm2) and 9.8 cm2 per knee (range, 2.5–31.6 cm2). Twenty-eight patients (50%) underwent concomitant osteotomies to address malalignment. There were 8 failures (14%); 6 of 15 (40%) in patients receiving workers’ compensation (WC) and 2 of 41 (4.9%) in non-WC patients. Additional arthroscopic surgical procedures were required in 24 patients (43%) for periosteal-related problems and adhesions; 88% of these patients experienced lasting improvement. At their latest available follow-up, 72% of patients rated themselves as good or excellent, 78% felt improved, and 81 % would again choose ACI as a treatment option. Conclusion Our results showed a failure rate of ACI in older patients that is comparable with rates reported in younger patient groups. The procedure is associated with a substantial rate of reoperations, mostly for the arthroscopic treatment of graft hypertrophy, similar to that in younger patients.

A 20-Year Follow-up After First-Generation Autologous Chondrocyte Implantation

Background: Treating articular cartilage defects is a demanding problem. Although several studies have reported durable and improved clinical outcomes after autologous chondrocyte implantation (ACI) over a long-term period, there is no report with over 20 years’ follow-up. Purpose: To evaluate clinical outcomes after first-generation ACI for the treatment of knees with disabling, large single and multiple cartilage defects for which patients wished to avoid prosthetic arthroplasty, with a minimum of 20 years’ follow-up. Study Design: Case series; Level of evidence, 4. Methods: The authors reviewed prospectively collected data from 23 patients (24 knees; mean age, 35.4 years [range, 13-52 years]) undergoing ACI for the treatment of symptomatic, full-thickness articular cartilage lesions. A mean of 2.1 lesions per knee were treated over a mean total surface area of 11.8 cm2 (range, 2.4-30.5 cm2) per knee. Kaplan-Meier survival analysis and functional outcome scores, including the modified Cincinnati Knee Rating System, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Short Form–36 (SF-36), were used. Patients also self-reported an improvement in pain with a visual analog scale and a satisfaction survey. Results: The 20-year survival rate was 63% (95% CI, 40%-78%). The evaluation of the 15 knees with retained grafts demonstrated that all clinical scores except the WOMAC subscore for stiffness and SF-36 mental component summary score improved significantly and were sustained to 20 years postoperatively. Ninety-three percent of these patients rated knee-specific outcomes as good or excellent. The outcomes for 9 of 24 knees were considered failures, including 5 undergoing revision ACI and 4 being converted to arthroplasty at a mean of 1.7 and 5.9 years, respectively. Only 1 of 5 knees that underwent revision ACI was converted to arthroplasty at 1.9 years after the index surgery, and the other 4 patients were able to maintain their biological knee. Overall, 20 years later, 79% of patients maintained their native knee, for which they initially sought treatment, and were satisfied when evaluated. Conclusion: First-generation ACI provided satisfactory survival rates and significant clinical improvements over a 20-year follow-up, which offers an important standard for comparison with newer-generation ACI technologies of the future.

Spontaneous Osteonecrosis of the Knee Treated with Autologous Chondrocyte Implantation, Autologous Bone-Grafting, and Osteotomy

Spontaneous osteonecrosis of the knee is a disease whose primary etiology remains unknown. First described by Ahlback et al.1 in 1968, it is now categorized as either primary (spontaneous) or secondary osteonecrosis2. Primary osteonecrosis usually presents in people over the age of fifty years, with sudden onset of pain, most frequently in the medial femoral condyle. Secondary osteonecrosis is associated with certain risk factors, such as corticosteroid therapy and alcohol use, and is usually encountered in younger people. In patients with advanced disease or for whom nonoperative treatment has failed, surgery is recommended, typically partial or total joint replacement3-5. Reports of non-arthroplasty procedures are limited. Debridement, curettage, microfracture surgery, osteochondral allograft, bone-grafting, and isolated high tibial osteotomy (HTO) have been proposed6-12, but none have demonstrated proven clinical outcomes in long-term follow-up studies. The recent widespread introduction of autologous chondrocyte implantation (ACI) into clinical practice has renewed interest in biologic treatment options for osteonecrosis of the knee. Recently, Adachi et al.13 showed excellent short-term results with the use of ACI in conjunction with interconnected porous hydroxyapatite (IP-CHA) bone substitute for the treatment of steroid-induced osteonecrosis. In our patients, the abnormal subchondral bone was addressed with an autologous bone graft because of its superior osteogenic, osteoconductive, and osteoinductive properties. We describe two cases of spontaneous osteonecrosis of the knee that were treated with ACI, autologous bone-grafting, and osteotomy and followed for seven and nine years. The patients were informed that data concerning their cases would be submitted for publication, and they provided consent. Case 1. A fifty-year-old man with a history of seizures treated with Keppra (levetiracetam), Depakote (valproic acid), and Lamictal (lamotrigine) experienced spontaneous onset of sharp pain in the medial aspect of the knee in June 2000. …

Long-term Outcomes of Autologous Chondrocyte Implantation in Adolescent Patients

Background: Treating symptomatic articular cartilage lesions is challenging, especially in adolescent patients, because of longer life expectancies and higher levels of functional activity. For this population, long-term outcomes after autologous chondrocyte implantation (ACI) remain to be determined. Purpose: To evaluate long-term outcomes in adolescents after ACI using survival analyses, validated outcome questionnaires, and standard radiographs. Study Design: Case series; Level of evidence, 4. Methods: We performed a review of prospectively collected data from patients who underwent ACI between 1996 and 2013. We evaluated 27 patients aged <18 years old (29 knees; mean age, 15.9 years) who were treated by a single surgeon for symptomatic, full-thickness articular cartilage lesions over a mean 9.6-year follow-up (median, 13 years; range, 2-19 years). A mean of 1.5 lesions per knee were treated over a mean total surface area of 6.2 cm2 (range, 2.0-23.4 cm2) per knee. Survival analysis was performed using the Kaplan-Meier method, with graft failure as the end point. The modified Cincinnati Knee Rating Scale, Western Ontario and McMaster Universities Osteoarthritis Index, visual analog scale, and Short Form 36 scores were used to evaluate clinical outcomes. Patients also self-reported knee function and satisfaction. Standard radiographs were evaluated using Kellgren-Lawrence grades. Results: Both 5- and 10-year survival rates were 89%. All clinical scores improved significantly postoperatively. A total of 96% of patients rated knee function as better after surgery, and all patients indicated that they would undergo the same surgery again. Approximately 90% rated knee-specific outcomes as good or excellent and were satisfied with the procedure. At last follow-up, 12 of 26 successful knees were radiographically assessed (mean, 5.6 years postoperatively), with no significant osteoarthritis progression. Three knees were considered failures, which were managed by autologous bone grafting or osteochondral autologous transplantation. Twenty knees required subsequent surgical procedures. These were primarily associated with periosteum and were arthroscopically performed. Conclusion: ACI resulted in satisfactory survival rates and significant improvements in function, pain, and mental health for adolescent patients over a long-term follow-up. ACI was associated with very high satisfaction postoperatively, despite the subsequent procedure rate being relatively high primarily because of the use of periosteum. If periosteum is used, this rate should be a consideration when discussing ACI with patients and their parents.

Intralesional Osteophyte Regrowth Following Autologous Chondrocyte Implantation after Previous Treatment with Marrow Stimulation Technique

Objective Bone marrow stimulation surgeries are frequent in the treatment of cartilage lesions. Autologous chondrocyte implantation (ACI) may be performed after failed microfracture surgery. Alterations to subchondral bone as intralesional osteophytes are commonly seen after previous microfracture and removed during ACI. There have been no reports on potential recurrence. Our purpose was to evaluate the incidence of intralesional osteophyte development in 2 cohorts: existing intralesional osteophytes and without intralesional osteophytes at the time of ACI. Study Design We identified 87 patients (157 lesions) with intralesional osteophytes among a cohort of 497 ACI patients. Osteophyte regrowth was analyzed on magnetic resonance imaging and categorized as small or large (less or more than 50% of the cartilage thickness). Twenty patients (24 defects) without intralesional osteophytes at the time of ACI acted as control. Results Osteophyte regrowth was observed in 39.5% of lesions (34.4% of small osteophytes and 5.1% of large osteophytes). In subgroup analyses, regrowth was observed in 45.8% of periosteal-covered defects and in 18.9% of collagen membrane–covered defects. Large osteophyte regrowth occurred in less than 5% in either group. Periosteal defects showed a significantly higher incidence for regrowth of small osteophytes. In the control group, intralesional osteophytes developed in 16.7% of the lesions. Conclusions Even though intralesional osteophytes may regrow after removal during ACI, most of them are small. Small osteophyte regrowth occurs almost twice in periosteum-covered ACI. Large osteophytes occur only in 5% of patients. Intralesional osteophyte formation is not significantly different in preexisting intralesional osteophytes and control groups.

Autologous Chondrocyte Implantation to Isolated Patella Cartilage Defects: Two- to 15-Year Follow-up

Background Autologous chondrocyte implantation (ACI) is a durable treatment for patients with chondral defects. This study presents the comprehensive evaluation of patients with patella defects treated with ACI at medium- to long-term follow-up. Methods Thirty consecutive patients with isolated chondral lesions of the patella were enrolled prospectively. Primary outcome measures were validated patient reported outcome measures and objective magnetic resonance imaging. Results Nineteen of 30 patients underwent tibial tubercle osteotomy (TTO) to correct lateral maltracking in combination with soft tissue balancing. The defect sizes were large, averaging 4.7 ± 2.1 cm2 (range 2.2-30.0 cm2). Pidoriano/Fulkerson classification revealed that 3 defects were type II (lateral), 9 were type III (medial), and 18 were type IV (central/panpatella). Age at the time of surgery was 32 ± 10 years. At follow-up of 2 to 14 years, knee function was rated good to excellent in 25 (83%) patients, fair in 4 (13%) patients, and poor in 1 (3%) patient. Three patients failed treatment after a mean of 75 months (6.25 years). All 3 failures were Workers Compensation (WC) cases. They were older than the non-WC patients, 42 ± 6 years compared with the non-WC 28 ± 9 years (P = 0.0019). Significant increases in all clinical and health utility outcome scores were seen. Magnetic resonance imaging demonstrated that the fill grade, surface and integrity of the repair tissue correlated with clinical scores. Conclusion ACI to isolated patella defects results in significant functional improvement at a minimum of 24 months, with the results remaining durable at latest follow-up of 15 years. Level of evidence Level 4.

Intermediate- to Long-Term Results of Combined Anterior Cruciate Ligament Reconstruction and Autologous Chondrocyte Implantation

Background: Cartilage injury associated with anterior cruciate ligament (ACL) ruptures is common; however, relatively few reports exist on concurrent cartilage repair with ACL reconstruction. Autologous chondrocyte implantation (ACI) has been utilized successfully for treatment of moderate to large chondral defects. Hypothesis: ACL insufficiency with relatively large chondral defects may be effectively managed with concurrent ACL reconstruction and ACI. Study Design: Case series; Level of evidence, 4. Methods: Patients undergoing concurrent ACL primary or revision reconstruction with ACI of single or multiple cartilage defects were prospectively evaluated for a minimum 2 years. Pre- and postoperative outcome measures included the modified Cincinnati Rating Scale (MCRS), Western Ontario and McMaster Universities Osteoarthritis Index, visual analog pain scales, and postsurgery satisfaction surveys. ACI graft failure or persistent pain without functional improvement were considered treatment failures. Results: Twenty-six patients were included, with 13 primary and 13 revision ACL reconstructions performed. Mean defect total surface area was 8.4 cm2, with a mean follow-up of 95 months (range, 24-240 months). MCRS improved from 3.62 ± 1.42 to 5.54 ± 2.32, Western Ontario and McMaster Universities Osteoarthritis Index from 45.31 ± 17.27 to 26.54 ± 17.71, and visual analog pain scale from 6.19 ± 1.27 to 3.65 ± 1.77 (all Ps <.001). Eight patients were clinical failures, 69% of patients were improved at final follow-up, and 92% stated they would likely undergo the procedure again. No outcome correlation was found with regard to age, body mass index, sex, defect size/number, follow-up time, or primary versus revision ACL reconstruction. In subanalysis, revision ACL reconstructions had worse preoperative MCRS scores and greater defect surface areas. However, revision MCRS score improvements were greater, resulting in similar final functional scores when compared with primary reconstructions. Conclusion: Challenging cases of ACL tears with large chondral defects treated with concurrent ACL reconstruction and ACI can lead to moderately improved pain and function at long-term follow-up. Factors associated with clinical failure are not clear. When combined with ACI, patients undergoing revision ACL reconstructions have worse function preoperatively compared with those undergoing primary reconstructions but have similar final outcomes.

Autologous Chondrocyte Implantation

Introduction Autologous chondrocyte implantation (ACI) for the treatment of articular cartilage lesions of the knee joint provides successful and durable long-term outcomes. Indications & Contraindications Step 1 Preoperative Planning Video 1 Obtain standing radiographs and magnetic resonance imaging (MRI) scans to identify all associated abnormalities (background factors). Step 2 Arthroscopic Assessment and Cartilage Biopsy Video 2 Evaluate the knee joint systematically and harvest cartilage tissue from the non-weight-bearing area. Step 3 Make the Incision for the Arthrotomy Video 3 Use a medial or lateral parapatellar arthrotomy and expose the lesion adequately. Step 4 Prepare the Defect Video 4 Debride all fissured and unstable articular cartilage surrounding the full-thickness chondral injury down to healthy contained cartilage. Step 5 Address Associated Abnormalities Address associated abnormalities (predisposing background factors) to optimize recovery and a successful outcome. Step 6 Prepare and Fix the Collagen Membranes Video 5 Orient the membrane patch with the rough surface to the subchondral bone and the smooth surface toward the articular surface; then sew it, tying the sutures knots on the membrane and not the cartilage, to tension it adequately throughout the entire defect. Step 7 Chondrocyte Implantation Video 6 Gently deliver the cells and fill the defect. Step 8 Postoperative Care (1) Initiate range-of-motion exercises to enhance chondrocyte regeneration and decrease the likelihood of intra-articular adhesion, (2) protect the graft from loading for 6 to 12 weeks after surgery to prevent graft overload and central degeneration or delamination of the graft, and (3) initiate isometric muscle exercises to regain muscle tone and prevent atrophy. Results ACI provided durable outcomes in 210 patients followed prospectively for 10 to 17 years after treatment with the first-generation ACI-periosteum technique6. Pitfalls & ChallengesRationale for the treatment of cartilage damage in younger patients depends on a thorough understanding of the predisposing factors for the chondrosis and the stage of disease. Implantation with autologous cultured chondrocytes allows for resurfacing of larger defect areas with reproducibly good/excellent results in 90% of patients with isolated lesions of the femoral condyle. Patellar lesions also may be successfully treated (approximately 75% improved) but strict attention must be given to correction of malalignment. Results in patients with tibial and salvage lesions are encouraging; however, these results should be viewed with caution due to the small number of patients with 2-year follow-up. Autologous chondrocyte implantation involves an open technique with the inherent disadvantages of adhesions and a more prolonged recovery. However, these disadvantages must be weighed against the procedures ability to produce a hyaline-type tissue with greater durability than fibrocartilage repairs produced by traditional marrow-stimulation techniques. We recommended matching the treatment procedure to patient expectations and lesion/demographic characteristics. Based on the available literature. algorithms have been published that recommend autologous chondrocyte implantation be reserved as first-line treatment for high-demand patients with large lesions (>2 cm2) and as revision therapy in patients with lesions of all sizes, regardless of patient demand, who have failed alternative marrow stimulation techniques.