Orthopedics

Feature Article 

Single-plug Autologous Osteochondral Transplantation: Results at Minimum 16 Years’ Follow-up

Giuseppe Filardo, MD, PhD; Elizaveta Kon, MD; Berardo Di Matteo, MD; Alessandro Di Martino, MD; Maurilio Marcacci, MD

Abstract

Different techniques have been proposed for the treatment of cartilage defects. Among the currently available options, autologous single-plug osteochondral transplantation is one of the few to be applied to address small and medium lesions. The goal of the current study was to document the long-term clinical outcome of a cohort of patients treated by this surgical strategy, which consists of harvesting a single osteochondral plug from a less weight bearing area of the knee and implanting it on the defect site by press-fit technique. Fifteen patients were enrolled. Age at surgery was 30.2±15.3 years, and body mass index was 22.5±3.0 kg/m2. The inclusion criteria were clinical symptoms, such as knee pain or swelling, and grade III to IV chondral and osteochondral knee lesions. Patients were prospectively evaluated up to a mean of 17.5±3.5 years of follow-up by using Lysholm, International Knee Documentation Committee (IKDC) subjective, and Tegner scores. A significant improvement was noted in all clinical scores. In particular, the IKDC subjective score increased from 34.5±23.6 to 66.3±26.4 (P=.001). The Lysholm score showed a similar trend. From a baseline value of 47.8±29.5, the score increased to 79.8±24.6 at the last evaluation (P=.001). A significant increase in Tegner score was observed at the 2-year evaluation, with stable results up to the last follow-up. Four failures were reported, which in 3 cases occurred at mid- to long-term follow-up, confirming that this technique can be considered a suitable option for the treatment of small and medium chondral and osteochondral lesions in young patients.

The authors are from the Nano-Biotechnology Laboratory (GF, EK) and the Biomechanics Laboratory (BD, AD, MM), II Orthopaedic Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy.

Drs Di Matteo and Di Martino have no relevant financial relationships to disclose. Dr Filardo is a consultant for and receives institutional support from Fin-Ceramica Faenza SpA (Italy), Fidia Farmaceutici SpA (Italy), and CartiHeal Ltd (Israel); is a consultant for EON Medica SRL (Italy); and receives institutional support from IGEA Clinical Biophysics (Italy), BIOMET (USA), and Kensey Nash (USA). Dr Kon is a consultant for CartiHeal Ltd (Israel); holds stock in CartiHeal Ltd (Israel); and received payment for presentations from Fin-Ceramica Faenza SpA (Italy) and Fidia Farmaceutici SpA (Italy). Dr Marcacci receives royalties and research institutional support from Fin-Ceramica Faenza SpA (Italy).

The authors thank Federica Balboni, Luca Andriolo, Francesco Perdisa, Francesco Tentoni, Giulia Venieri, Letizia Merli, Elettra Pignotti, and Keith Smith (Rizzoli Orthopaedic Institute, Bologna, Italy) for their support in preparing this manuscript.

Correspondence should be addressed to: Berardo Di Matteo, MD, Biomechanics Laboratory, II Orthopaedic Clinic, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy ( berardo.dimatteo@gmail.com).

Received: October 03, 2013
Accepted: January 30, 2014
Posted Online: September 09, 2014

Abstract

Different techniques have been proposed for the treatment of cartilage defects. Among the currently available options, autologous single-plug osteochondral transplantation is one of the few to be applied to address small and medium lesions. The goal of the current study was to document the long-term clinical outcome of a cohort of patients treated by this surgical strategy, which consists of harvesting a single osteochondral plug from a less weight bearing area of the knee and implanting it on the defect site by press-fit technique. Fifteen patients were enrolled. Age at surgery was 30.2±15.3 years, and body mass index was 22.5±3.0 kg/m2. The inclusion criteria were clinical symptoms, such as knee pain or swelling, and grade III to IV chondral and osteochondral knee lesions. Patients were prospectively evaluated up to a mean of 17.5±3.5 years of follow-up by using Lysholm, International Knee Documentation Committee (IKDC) subjective, and Tegner scores. A significant improvement was noted in all clinical scores. In particular, the IKDC subjective score increased from 34.5±23.6 to 66.3±26.4 (P=.001). The Lysholm score showed a similar trend. From a baseline value of 47.8±29.5, the score increased to 79.8±24.6 at the last evaluation (P=.001). A significant increase in Tegner score was observed at the 2-year evaluation, with stable results up to the last follow-up. Four failures were reported, which in 3 cases occurred at mid- to long-term follow-up, confirming that this technique can be considered a suitable option for the treatment of small and medium chondral and osteochondral lesions in young patients.

The authors are from the Nano-Biotechnology Laboratory (GF, EK) and the Biomechanics Laboratory (BD, AD, MM), II Orthopaedic Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy.

Drs Di Matteo and Di Martino have no relevant financial relationships to disclose. Dr Filardo is a consultant for and receives institutional support from Fin-Ceramica Faenza SpA (Italy), Fidia Farmaceutici SpA (Italy), and CartiHeal Ltd (Israel); is a consultant for EON Medica SRL (Italy); and receives institutional support from IGEA Clinical Biophysics (Italy), BIOMET (USA), and Kensey Nash (USA). Dr Kon is a consultant for CartiHeal Ltd (Israel); holds stock in CartiHeal Ltd (Israel); and received payment for presentations from Fin-Ceramica Faenza SpA (Italy) and Fidia Farmaceutici SpA (Italy). Dr Marcacci receives royalties and research institutional support from Fin-Ceramica Faenza SpA (Italy).

The authors thank Federica Balboni, Luca Andriolo, Francesco Perdisa, Francesco Tentoni, Giulia Venieri, Letizia Merli, Elettra Pignotti, and Keith Smith (Rizzoli Orthopaedic Institute, Bologna, Italy) for their support in preparing this manuscript.

Correspondence should be addressed to: Berardo Di Matteo, MD, Biomechanics Laboratory, II Orthopaedic Clinic, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy ( berardo.dimatteo@gmail.com).

Received: October 03, 2013
Accepted: January 30, 2014
Posted Online: September 09, 2014

Cartilage is one of the most challenging tissues to treat because of its limited healing potential.1 This is a consequence of peculiar morphologic and functional features that up to now have been impossible to restore. The increasing incidence of cartilage lesions and the huge interest in this particular field of musculoskeletal medicine led to the development of several strategies, both reparative and regenerative,2 whose clinical results, in most cases, have been widely reported up to mid- and long-term evaluation.3–6 Cartilage surgery is no longer in its infancy, but the scientific community is still debating intensely about the best treatments for chondral and osteochondral lesions. Different techniques have been proposed for the treatment of the same kind of defect, but there is no agreement on which approach is preferable according to patient and lesion characteristics.7 Furthermore, indications vary widely because some authors restrict cartilage treatment to focal traumatic lesions,8 whereas others suggest that if concurrent comorbidities, such as instability, meniscal pathology, and axial misalignment, are addressed, even “complex” knee lesions can benefit from cartilage treatment.9–12 To shed light on this controversial field, it is important to assess the long-term efficacy of the procedures proposed because patients who undergo cartilage treatment are often young and active. Therefore, the “ideal” treatment should provide clinical benefit as long as possible.

Based on the current evidence, several surgical strategies have been investigated, ranging from classic microfracturing3 to the most recent cell-based therapies or cell-free approaches based on “smart” biomimetic scaffolds.13–15 Each technique has advantages and limits. Therefore, surgeons should evaluate every option before deciding how to proceed. Treatments such as mosaicplasty, autologous or allogeneic osteochondral transplantation, autologous chondrocyte implantation, matrix-assisted autologous chondrocyte transplantation, and osteochondral scaffolds can be considered as possible treatments for cartilage pathology.2 However, in the case of regenerative solutions, such as autologous chondrocyte transplantation or biomaterials, the higher cost and regulatory limitations must be considered. Expensive and high-tech procedures are often available only in highly specialized centers and are not an option for many orthopedic surgeons. Therefore, besides the fashionable and ambitious new regenerative treatments, there is still space for less expensive and easily available treatments to address the damaged osteochondral unit. Among these, mosaicplasty and single-plug autologous osteochondral transplantation are still viable solutions.

These approaches present some analogies in terms of both treatment rationale and technical aspects. Both procedures consist of harvesting autologous osteochondral grafts from a healthy region of the knee to be placed in the defect site. Looking at mosaicplasty, the arthroscopic approach and the possibility of harvesting multiple small cylinder-shaped autografts from different articular sites make this technique less invasive and contribute to less donor site morbidity, which in theory should allow for the treatment of larger lesions. Conversely, some studies have shown that the number of plugs used to cover the defect area correlates with poorer clinical outcomes,16 probably because it is technically very challenging to reconstruct the physiologic convexity of the condylar cartilaginous surface with plugs harvested from different joint sites. In addition, the cylindrical shape of the grafts does not allow optimal coverage of the lesion site, leaving residual small uncovered areas that might impair or diminish the healing process. The particular technique of single-plug autologous osteochondral transplantation described in this study allows nearly perfect filling of the defect, thus promoting better stability and better bone-to-bone and cartilage-to-cartilage healing, but it also presents greater invasiveness.17 This approach requires arthrotomic exposure and may cause greater donor site morbidity than mosaicplasty because of the size of the plug harvested, which might become symptomatic despite being located in a less weight bearing zone.

Thus, both approaches have advantages and disadvantages, but whereas several studies have reported long-term clinical evaluation of mosaicplasty, no studies have documented the long-term outcome of this particular arthrotomic, single-plug osteochondral autograft technique. Therefore, the goal of the current study was to document the long-term clinical results of a series of 15 patients treated with autologous osteochondral transplantation and followed up for a mean of 17.5 years.

Materials and Methods

Patient Selection

The current study was approved by the hospital ethics committee and internal review board, and informed consent was obtained from all patients.

Fifteen patients (9 men and 6 women) were enrolled and treated. Mean age was 30.2±15.3 years, and mean body mass index was 22.5±3.0 kg/m2. The inclusion criteria were clinical symptoms, such as knee pain or swelling, and grade III–IV chondral and osteochondral lesions of the knee. Exclusion criteria were uncorrected axial deviation and knee instability. Axial deviation and knee instability were evaluated clinically and via radiograph. Patients who presented with significant knee axial deviation (>5°) underwent corrective osteotomy in the same surgical session as the osteochondral grafting. Patients with infectious, neoplastic, metabolic, and inflammatory pathology were also excluded.

Two patients were lost to follow-up, so their data could not be included in the statistical analysis.

Lesion size ranged from 1.5 to 4.5 cm2. Defects included 10 medial femoral condyles and 3 lateral femoral condyles. The etiology was osteochondritis dissecans in 5 cases and osteonecrosis in 6 cases. The cause was degenerative in 1 patient and posttraumatic in 1 case.

Before symptom onset, 3 patients practiced competitive sports (2 soccer and 1 basketball) (preinjury Tegner score, ≥7), whereas 9 patients were amateur athletes (preinjury Tegner score, 3–6). Only 1 patient, the one with degenerative etiology, was not involved in any sport (Tegner score, <3). Eight patients were treated for the first time, whereas 5 patients had undergone previous surgery, including 1 high tibial osteotomy and 4 medial meniscectomies. In 3 patients, other combined procedures were performed during the same operation: 1 patellar realignment and lateral release and 2 distal femoral osteotomies.

Surgical Procedure

Surgery was performed with an arthrotomic approach. After exposure of the articular surface, the osteochondral defect was identified and all fibrous tissue was excised down to a base of cancellous bone. The depth of the graft site and the amount of bone resected were as large as necessary to reach bleeding bone on all sides of the defect. The osteochondral graft was removed from the donor zone on the superior aspect of the lateral femoral condyle, preserving the patellar groove. The graft bone was carefully contoured so that it fit precisely into the recipient bed. Graft thickness was equal to the recipient site depth so that the graft cartilage surface did not sit either above or below the articular cartilage level of the femoral condyle. In most cases, sufficient graft stability was achieved with press-fit fixation, whereas in a few cases, screw fixation was used. Then drainage was placed, and the wound was closed in layers.

Postoperative management focused on early mobilization to facilitate faster resolution of swelling, promote healing and joint nutrition, and prevent adhesions. On the second postoperative day, self-assisted mobilization of the knee or continuous passive motion for 6 hours daily with 1 cycle/min was recommended until 90° of flexion was reached. Patients did not usually require more than 2 weeks of continuous passive motion. Early isometric and isotonic exercises and controlled mechanical compression were performed. Voluntary muscular contraction and electrical neuromuscular stimulation were indicated and could be started on patient discharge. After 45 days, weight touch-down with crutches was allowed, and the patient could then move gradually toward full weight bearing, usually at 8 weeks. Active functional training was then started, with the goal of returning to a correct running pathway by proprioceptive muscular strengthening, endurance exercises, and aerobic training.

Patient Evaluation

Patients were prospectively followed for a mean of 17.5±3.5 years (range, 16–24 years). Clinical outcomes of all patients were analyzed using the Lysholm score and the International Knee Documentation Committee (IKDC) subjective score. Returning to participation in sports was also evaluated using the Tegner score and compared with preoperative and preinjury levels. Adverse events and failures were also recorded. Failure was defined as the need for reintervention because of symptoms related to the primary osteochondral defect. In the case of unsuccessful treatment, the last scores before reintervention were reported for analysis at subsequent follow-up.

Statistical Analysis

All continuous data were expressed as mean and standard deviation; categorical variables were expressed as frequency and percentages. The Wilcoxon nonparametric test was used to test the differences at different follow-up times. The Mann-Whitney nonparametric test was performed to assess between-group differences of continuous data. The Spearman rank correlation was used to assess correlation between rank and continuous data, and the Kendall tau ordinal correlation was used to assess correlation of ordinal data. Fisher’s chi-square test was performed to investigate the relationships between dichotomous variables. Pearson’s chi-square test evaluated by exact methods for small samples was performed to investigate the relationships between grouping variables. All nonparametric tests were evaluated by exact methods for small samples. Kaplan-Meier survival analysis was performed to assess overall survival, the log-rank test was used to investigate the influence of categorical variables on survival, and Cox regression analysis was used to investigate the influence of continuous variables on survival. For all tests, P<.05 was considered significant. All statistical analysis was performed with SPSS, version 19.0 (IBM, Armonk, New York).

Results

No severe adverse events were reported in the current series.

Significant improvement was found in all clinical scores. In particular, the IKDC subjective score increased from 34.5±23.6 at baseline to 66.3±26.4 at final follow-up (P=.001; Figure 1). The Lysholm score showed a similar significant trend. From a baseline value of 47.8±29.5, the score increased to 79.8±24.6 at the last evaluation (P=.001; Figure 2). A significant increase occurred in the Tegner score at the 2-year evaluation, and the score remained stable up to the last evaluation (Figure 3). In fact, the mean sport activity level increased from 2.46±2.1 (preoperative level) to 3.9±2.5 at the 2-year evaluation (P=.006), which was confirmed (4.1±2.6) at the last follow-up (not significant). Despite this positive trend, the majority of patients were not able to regain the same pre-injury sport activity level, as shown by the significant difference remaining between preinjury and final Tegner scores (5.6±2.3 vs 4.1±2.6; P=.016).

International Knee Documentation Committee subjective score improvement from preoperatively to a mean of 17.5 years of follow-up.

Figure 1:

International Knee Documentation Committee subjective score improvement from preoperatively to a mean of 17.5 years of follow-up.

Lysholm score improvement from preoperatively to a mean of 17.5 years of follow-up.

Figure 2:

Lysholm score improvement from preoperatively to a mean of 17.5 years of follow-up.

Tegner score improvement: evaluation at preinjury (pre-inj), pre-treatment (pre-op), 2-year follow-up, and final long-term follow-up.

Figure 3:

Tegner score improvement: evaluation at preinjury (pre-inj), pre-treatment (pre-op), 2-year follow-up, and final long-term follow-up.

The current series had 4 treatment failures (Figure 4). In the first case, no clinical improvement was obtained. The patient sought other treatment at a different medical center and was not available for further interview by the current authors. The second patient was treated again 13 years after the osteochondral autograft and underwent implantation of a biomimetic 3-layered osteochondral scaffold on the medial femoral condyle. The operation was performed in the authors’ division, and after 3 years, the clinical condition was satisfactory and the patient reported improvement in pain and knee function. The third patient was treated after 14 years by total knee arthroplasty because of the development of diffuse osteoarthritis. The last patient was treated again 8 years after osteochondral autograft transplantation at another medical center by microfracturing in the same area. Because the patient could not be contacted for an interview, no data are available on the clinical outcome.

Cumulative survival rate up to the maximum follow-up evaluation of the current study (24 years postoperatively).

Figure 4:

Cumulative survival rate up to the maximum follow-up evaluation of the current study (24 years postoperatively).

Because of the low number of patients included in the current study, no statistical correlation could be found among clinical outcomes and parameters that might influence the results, such as etiology, previous surgeries, combined surgeries, sex, or body mass index.

Discussion

The main finding of the current study was that single-plug autologous osteochondral transplantation can provide a good clinical outcome and improvement in knee functional status, with stable results at very long-term evaluation.

The treatment of cartilage pathology is a topic of intense preclinical and clinical research, and mid- and long-term outcomes of some procedures, both reparative and regenerative, have been described. For the regenerative approach, several cell-based or scaffold-based procedures have been proposed, but they are all limited by high cost and regulatory limitations. Despite the goal of restoring an optimal articular surface, no treatment has clearly proven to regenerate hyaline tissue or clearly exceed the results obtained with less expensive and widely available traditional procedures.15,16,18 The classic reparative approach is bone marrow stimulation. Despite being developed decades ago, this technique is still widely applied. In 2003, Steadman et al3 published their results in a cohort of 72 patients treated with microfractures and evaluated at a mean of 11 years of follow-up. Clinical outcome was satisfactory, and the authors reported superior results for patients younger than 35 years. The same trend was shown by Kreuz et al,19 who noticed that patients older than 40 years with patellofemoral lesions had poorer clinical results. Besides the commonly reported good short-term results, more controversial is the long-term outcome, with evidence of progressive worsening over time.20 Mosaicplasty offered a good clinical outcome. Hangody et al21 reported the clinical outcome of the largest series (831 patients), with 92% good to excellent results for femoral condyle defects at short-term follow-up, confirmed in a further evaluation at a mean of 9 years (although the follow-up interval was rather inhomogeneous, ranging from 2 to 17 years). Other reports confirmed good results at mid- to long-term follow-up.22–24 However, after reporting marked early improvement, Solheim et al25 observed significant clinical deterioration between 5 and 9 years of follow-up. In a further evaluation 10 to 14 years after surgery,26 they observed a general poor outcome in 40% of the 73 patients treated, but noted good results in younger men with small lesions. The indication for treatment is probably the key to explaining these heterogeneous results. For example, Ollat et al27 reported significant clinical improvement, with an 82% satisfaction rate, in a large cohort of patients at 8 years of follow-up, especially in men with small lesions, osteochondritis dissecans, a medial femoral condyle site, and short preoperative duration of symptoms. Marcacci et al16 confirmed that this technique can offer good clinical and imaging results,28 but only in small lesions that require a limited number of plugs.

In contrast to the abundant literature on mosaicplasty, only a few studies have reported different kinds of single-plug techniques, such as the one used in the current study. Outerbridge et al29 harvested a single autograft from the lateral facet of the patella to minimize donor site morbidity. A satisfactory clinical outcome was obtained in each of the 10 patients evaluated at a mean of 6.5 years of follow-up, but mild anterior knee pain occurred in 4 cases, flexion limitation in 2, and the formation of small osteophytes in the donor area in 5 cases. These osteophytes were associated with anterior pain in 3 cases and mild patellar tilt in 2 cases. Marcacci17 et al reported mid-term results after using an autologous osteochondral plug, harvested from the superior part of the lateral condyle, to fill femoral condyle defects. They reported that 12 of 13 patients had a good clinical outcome and returned to their preinjury level of activity at a mean of 61.5 months, and radiographs showed good integration of the plug. The procedure has also been tested for large osteochondral condylar defects. Agneskirchner et al30 treated 29 patients with a mean defect size of 7.2 cm2 by harvesting a single graft from the posterior femoral condyle, which was then fixed either by a screw or by press-fit. Twenty-six patients had reduced pain and swelling at a mean of 17.7 months, and 3 were not satisfied, whereas magnetic resonance imaging showed good viability of the graft. No complications related to the graft were reported at this short follow-up time, and the authors pointed out the advantages of using a single graft for better rendering joint congruence.

The single-plug approach offers the opportunity to fill the lesion site perfectly with a graft sized to match the ostechondral defect, thus allowing optimal bone-to-bone and cartilage-to-cartilage healing. However, there is a risk of donor site morbidity, especially considering the size of the graft, which cannot be neglected. Some studies specifically focused on this aspect and tried to prove and quantify the risk of morbidity. LaPrade and Botker31 documented 2 patients who required shaving of fibrous hypertrophy or filling with fresh osteochondral allograft to address persistent knee pain after osteochondral plug harvesting. Valderrabano et al32 used the knee as a donor joint to treat ankle joint defects and observed a significant increase in the mean visual analog scale score of the harvested knee in 6 cases (50%). The pain was completely resolved in 5 of 6 patients at 1 year of follow-up. Cartilage changes, joint space narrowing, and cyst formation were detected in all except 1 knee on magnetic resonance imaging, and focal radioisotope uptake was abnormal on single-photon emission computed tomography in 7 of 12 knees. However, no correlation was found with clinical outcome. Paul et al33 reported 112 patients (of 200) with asymptomatic donor knees before the procedure who had a marked reduction in the Lysholm score at short-term follow-up, followed by a progressive increase over time to mid-term follow-up. Neither the total area of harvest nor the number of plugs had any influence, whereas higher body mass index negatively influenced the outcome. Finally, Reddy et al34 reported that 9 of 11 patients had a decreased Lysholm score in previously asymptomatic donor knees at 28 to 77 months of follow-up after knee-to-talus osteochondral grafting. No correlation was found with respect to the harvest technique, either arthrotomy or arthroscopy, or the number of grafts used. In light of these remarks, donor site morbidity is an important factor that might affect the overall outcome of the procedure, thus jeopardizing joint homeostasis and results over time.

The current study evaluated the results obtained after an autologous transplantation procedure at very long-term follow-up. Despite the invasiveness of the arthrotomic approach35 and the size of the osteochondral plug harvested, this study showed that this technique can provide clinically significant improvement and a stable outcome over time.

This finding is important because patients undergoing cartilage procedures are often young and demanding, and therapeutic options should provide long-lasting beneficial effects to avoid the need for early reintervention with more invasive procedures. Furthermore, the need to reduce costs and the different reimbursement policies applied in different countries make cartilage procedures a “keep-an-eye-on” treatment because modern cell-based and biomaterials-oriented technologies are not always available or feasible.36 The strength of osteochondral grafting is also obvious from this point of view. Despite being less modern or innovative, there is still space for its application in clinical practice. Therefore, it is important to report indications, limits, and results over time.

However, the current study has some limitations, which are the small number of patients treated (which did not allow for subanalysis to determine the correlation between size and outcome and to identify a size threshold to avoid donor site morbidity), the lack of a control group, and lack of imaging evaluation. Despite these limitations, to the authors’ knowledge, this is the first trial to report clinical data on this particular technique at long-term follow-up, showing overall good clinical results. The very long-term mean 17 years of follow-up allowed documentation of both stable general clinical improvement and failure over time. All treatment failures except 1 occurred at mid- to long-term evaluation. Therefore, most of the patients who failed actually benefited from this procedure for several years. This technique can be considered as a suitable treatment option for small and medium chondral and osteochondral knee lesions. However, larger studies are needed to better identify patients who may benefit from this procedure, in particular, in terms of size-related risk of donor site morbidity.

Conclusion

Single-plug autologous osteochondral transplantation is a safe, 1-step, and cost-effective procedure for the treatment of small and medium chondral and osteochondral lesions. This technique provided overall good results, even over the long term. Direct transplantation of a viable autologous osteochondral unit did not avoid failure over time in a considerable number of cases. However, even if treatment was unsuccessful in some of the patients and further operations were needed, most patients showed marked clinical improvement for several years.

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