Clinical Outcomes of Patellar Chondral Lesions Treated with Juvenile Particulated Cartilage Allografts

Abstract

Background

Juvenile particulated cartilage allograft (DeNovo NT®, Zimmer, Warsaw, IN) transplantation is a relatively new technology for the treatment of high-grade cartilage lesions. To date there is limited literature demonstrating its effectiveness and safety. The present study specifically looks at the short-term efficacy of DeNovo NT® allograft for symptomatic high-grade cartilage lesions of the patella. Clinical outcomes and complications are reported.

Methods

Seventeen cases of DeNovo NT® allograft transplantation at our institution were retrospectively reviewed from 2010 to 2013. Thirteen patients had the procedure performed for patellar lesions and are included in the present study. A chart review was performed to record demographic data, surgical technique, and complications. In addition, we analyzed preoperative and postoperative KOOS outcome scores.

Results

The mean age was 22.5 years (range, 14 - 34), with 3 males and 10 females. Mean follow-up was 8.2 months (range, 0.67 - 32.7). Six of the patients had concomitant anteromedialization of the tibial tubercle. DeNovo NT® allograft transplantation resulted in improvement for each outcome measure used. Overall KOOS score significantly improved from a mean of 58.4+15.7 to 69.2+18.6 (P = 0.04). Improvement in KOOS subscales of pain, ADL, and symptoms all approached but did not reach statistical significance (P values between 0.05 and 0.10). There were no infections or hardware complications.

Conclusions

This series demonstrates that DeNovo NT® allograft transplantation for symptomatic high-grade cartilage lesions of the patella results in pain relief and improved outcomes in the short term.

Further studies are needed to better evaluate this new technology.

Level of Evidence: Level IV, therapeutic case series

Introduction

Cartilage lesions of the patella are a difficult problem that can cause significant pain and functional limitation in patients. These lesions have demonstrated poor capacity to heal spontaneously^1,2 and frequently require surgical treatment. There are multiple surgical options for these lesions, including microfracture, osteochondral autograft transfer, osteochondral allograft transplantation, and autologous chondrocyte implantation (ACI). Microfracture³ and ACI⁴ have been less successful in treating patellar lesions than femoral condylar lesions, thought to be secondary to the insufficient quality of the repair tissue. Osteochondral transplant is not feasible for many patellar lesions given the patellar contour, hard subchondral bone, and limited bone depth. Tibial tubercle osteotomies with anteriorization can also be used alone or in conjunction with the above procedures in an attempt to unload the lesion and improve outcomes. More recently, juvenile particulated cartilage transplantation (DeNovo NT®, Zimmer, Warsaw, IN) has been used for patellar lesions with success⁵. Multiple studies have demonstrated that chondrocytes from particulated cartilage can migrate to form new hyaline-like repair tissue that integrates with surrounding tissue^6-8. This procedure is relatively new and there is limited literature supporting its effectiveness for patellar lesions. The present study represents a retrospective analysis of clinical outcomes for patients undergoing juvenile particulated cartilage transplantation for patellar lesions at our institution.

Materials and Methods

Patients

Between 2010 and 2013, 17 patients at our institution underwent juvenile particulated cartilage transplantation for full-thickness cartilage lesions of the knee by one of three senior authors (JPA, BRW, and MB). After institutional review board approval, we retrospectively reviewed their charts for demographic information, operative reports, clinic notes, complications, and preoperative and postoperative (Knee injury and Osteoarthritis Outcome Score) KOOS scores. Four of these patients had lesions of the femoral condyle or tibial plateau and were excluded from the present analysis. An additional four patients did not have pre-operative KOOS scores. Thus, 13 patients were analyzed for complications and a total of nine patients were analyzed for functional outcomes measures. The final analysis included 13 patients, ranging in age from 14 -54 (mean 22.5), with three males and 10 females. Mean follow-up was 8.2 months (range, 0. 67 - 32.7). All participants had full-thickness patellar defects identified on preoperative MRI. The indication for surgery was persistent anterior knee pain refractory to nonoperative treatment. The indication for concomitant tibial tubercle osteotomy was patellar malalignment and patellofemoral pain. This was performed in six total patients (Table 1).

Table 1.

Patient Demographic Data. Patients 10-13 did not have pre-operative KOOS scores and only analyzed for complications.

Patient No.	Gender	Age	Side	Size (mm)	Procedure	Complication
1	Female	14	Left	10X20	Fulkerson & DeNovo NT® Patella	None
2	Female	16	Right	20X20	Fulkerson & DeNovo NT® Patella	Pes anserine Bursitis
3	Male	14	Left	15X20	Fulkerson & DeNovo NT® Patella	Quad weakness
4	Female	15	Right	15X20	DeNovo NT® Patella	Lumbar plexopathy
5	Female	36	Right	5X5	DeNovo NT® Patella	None
6	Male	26	Right	12X15	DeNovo NT® Patella	None
7	Female	25	Left	8X12	DeNovo NT® Patella	None
8	Male	22	Left	6X20	DeNovo NT® Patella	None
9	Female	18	Right	15X15	DeNovo NT® Patella	None
10	Female	54	Right	10X25	DeNovo NT® Patella	Lumbar plexopathy
11	Female	37	Left	5X15	Fulkerson & DeNovo NT® Patella	Quad weakness
12	Female	19	Left	8X12	Fulkerson & DeNovo NT® Patella	None
13	Female	36	Right	25X28	Fulkerson & DeNovo NT® Patella	None

DeNovo NT® Surgical Procedure

After induction of anesthesia and administration of appropriate preoperative antibiotics, the operative leg was prepared and draped in sterile fashion. A standard parapatellar arthrotomy was made, allowing eversion the patella. In cases with associated tibia tubercle osteotomy, the osteotomy was performed first and the patella cartilage resurfacing was done prior to fixation of the osteotomy. The patellar defect was outlined with a scalpel, and remaining cartilage was carefully removed from the lesion base using a curette, being sure to leave vertical walls at the periphery of the lesion. DeNovo NT® graft was applied in one of two methods. The first method is that classically described by Farr et al⁹, filling a foil template with the particulated cartilage pieces along with fibrin glue, and transplanting this into the defect en bloc. Alternatively, in some cases the cartilage pieces were laid directly into the base of the lesion and then covered with fibrin glue, as has also been described for a patellar lesion⁵ (Figure 1). Care was taken to ensure that the fibrin glue cartilage construct was not proud relative to the surrounding native cartilage. After allowing the repair construct to cure, the arthrotomy was closed and the wound closed in standard fashion or attention was turned to completion of the tibial tubercle osteotomy.

Figure 1. Intra-operative images indicating procedural steps in 2 patients. Row 1: Cartilage defect after debridement. Row 2: implantation of DeNovo NT® cartilage, Row 3: application of fibrin glue.

Tibial Tubercle Osteotomy Procedure

Six of 13 patients underwent a concomitant tibial tubercle osteotomy at the time of the patellar procedure to address patellar alignment. Prior to surgery, the Tibial Tuberosity-Trochlear Groove (TT-TG) distance, as calculated by measuring the distance from the tibial tuberosity to the deepest portion on the trochlear groove on parallel, superimposed axial CT images¹⁰ was calculated. In six cases the TT-TG distance, the TT-TG distance was greater than 10mm and thus patients were indicated for tibial tubercle osteotomy.

The osteotomy was carried out in the standard dovetail fashion, then the patellar lesion as addressed using the DeNovo NT® graft as outlined above, and finally, the tubercle was translated and fixed anteromedially based on intra-operative patellar tracking.

Rehabilitation

Post-operatively, patients without a concomitant Fulkerson osteotomy were placed in hinged knee brace with weight bearing as tolerated with knee locked in extension when ambulatory. Patients then began the standard microfracture post-operative physical therapy, focused on quadriceps strengthening at approximately 2 weeks post-operatively. Patients with Fulkerson osteotomy were non-weight bearing for 6 weeks with seated range of motions and brace locked in extension at all other times. Then, patients began a standard post-operative lower extremity strengthening rehabilitation protocol. Patients were then followed with regular follow up visits at 2 weeks, 6 weeks, 3 months and 6 months.

Second-Look Arthroscopy

A second-look arthroscopy was performed in one patient. The arthroscopy was performed in the standard fashion with establishment of anteromedial, anterolateral and superolateral outflow portals. A standard diagnostic arthroscopy was performed and no additional surgical procedures were performed at time of arthroscopy.

Statistical Analysis

Patient data was compiled in a spreadsheet database, and statistical calculations were performed utilizing the spreadsheet software (Microsoft Excel, Redmond, Washington). A two-tailed t-test was performed comparing preoperative and postoperative scores for overall KOOS as well as each of the KOOS subscales.

Results

Clinical Outcomes

Juvenile articular cartilage transplantation resulted in improvement in all outcomes measured (CHART 1). The overall KOOS score improved from a mean of 58.4+15.7 to 69.2+18.6 (P = 0.04), which achieved significance (Table 2). Improvement in KOOS subscales of pain, Activities of Daily Living (ADL), symptom and WOMAC function all approached but did not reach statistical significance (P values between 0.05 and 0.10).

Chart 1. Graphic depiction of improvement in KOOS subscales at average of 6 months. * Note statistical significance of KOOS overall.

Table 2.

Results of KOOS subscales: paired two-sample t-test for means.

Test	Pre-surgical mean	Post-surgical mean	P(T<=t) two-tail
KOOS overall	58.41	69.20	0.04
KOOS ADL	69.16	78.42	0.10
KOOS pain	62.96	72.60	0.07
KOOS QOL	33.33	43.52	0.31
KOOS Sports and Rec	30.00	39.03	0.47
KOOS Symptom	56.74	70.63	0.10
KOOS WOMAC function	69.16	78.42	0.10
KOOS WOMAC pain	72.22	78.33	0.22
KOOS WOMAC stiffness	56.94	68.06	0.21

Complications

Of the 13 patients that met criteria for inclusion in the study, two had post-operative lumbar plexopathies manifested by lower extremity weakness and likely associated with the pre-operative femoral nerve block given the distribution of weakness. One patient responded well to physical therapy and the plexopathy and weakness resolved. The other patient had continued weakness at last follow up. Two other patients developed post-operative quadriceps weakness, not associated with a lumbar plexopathy. One patient weakness resolved with physical therapy and the other patient had continued weakness at last follow-up. Both of these patients had a concomitant Fulkerson procedure performed at the time of cartilage transplantation. Another patient developed pes anserine bursitis and painless crepitus with range of motion of the knee. This was resolving with physical therapy at last follow-up. This patient also had a concomitant Fulkerson procedure (Table 1).

Discussion

There are multiple surgical options for treatment of cartilage lesions of the patella, including microfracture, osteochondral autograft transfer, osteochondral allograft transplantation, autologous chondrocyte implantation, and, more recently, transplantation of juvenile particulated cartilage¹¹. The successful restoration of hyalinelike cartilage in animal models⁷, and the ability of this cartilage to potentially restore adult damaged articular cartilage^12,13 has been reported. The conceptual use of juvenile particulated cartilage for chondral defects has been theorized for some time, ¹³ but its clinical use in patellar chondral lesions is a relatively new concept ¹⁴.There is a paucity of literature supporting its effectiveness.

DeNovo NT® has been available for clinical use since 2007 and been used successfully for treatment of osteochondral dissecans (OCD) lesions of the talus^15-17. A recent case report by Bonner et al.,⁵ reported improved International Knee Documentation Committee (IKDC) and KOOS subscale scores at 2 years with MRI evidence of resolution of chondral defect at 21 months. Similarly, another case report by Thompkins et al., ¹⁸ found improved IKDC and KOOS subscale scores and MRI evidence of chondral defect resolution at a minimum of 18 months. Our study also indicates improvement in functional outcomes measures at short-term follow-up and augments the effectiveness of juvenile particulated cartilage in treatment of patellar chondral lesions. There were no infections or issues directly related to use of the DeNovo NT® graft in our series.

Traditionally, indications for a Fulkerson osteotomy include unloading of patella cartilage lesions for lateral patella overload or early degenerative changes as well as treating patellofemoral instability in the presence of a lateral tracking vector. Anteromedialization decreases total distal and lateral patellofemoral contact pressure and lateral trochlea compression¹⁹. The addition of a tibia tubercle or Fulkerson osteotomy was used in 6/13 cases to unload the patella cartilage lesion. The tubercle osteotomy makes the patella cartilage resurfacing easier because the patella can be flipped over through the osteotomy improving access and exposure. The question remains whether the cartilage resurfacing procedure, the unloading osteotomy, or both are needed to decrease pain and improve function in patients with patella cartilage lesions. The key to surgical planning is to know the lesion location and the TT-TG distance, which is calculated by measuring the distance from the tibial tuberosity to the deepest portion on the trochlear groove on parallel, superimposed axial CT images.¹⁰

We recommend an isolated anteromedialization (Fulkerson) osteotomy for lateral patella lesions. When the TT-TG distance is greater than 15 mm, it is important to move the tubercle fragment both anteriorly and medially. When the TT-TG is less than 10 mm, the tubercle should only be shifted anteriorly. For medial and central patella lesions, we recommend an osteotomy and cartilage resurfacing procedure. Similar to lateral lesions, the TT-TG distance determines the degree and amount of anterior or medial translation. If alignment is corrected (TT-TG less than 12 mm) and there is no instability, success rates of cell based cartilage resurfacing is around 70%²⁰.

The results of this study indicate that the use of DeNovo NT® cartilage in the treatment of patellar chondral defects is a viable option for patients with identified chondral defects. However, there are several disadvantages to the use of DeNovo NT®, including: risks with use of allograft, cost, inability to put the product back on the shelf once opened, and need for an arthrotomy. These disadvantages should be thoroughly considered prior to use of DeNovo NT®.

There is a potential risk of disease transmission with any allogenic transplantation and this hold true with the use of DeNovo NT®. However, several studies have indicated that the use of allogenic chondrocytes is safe and the risk of transmission is low given that native chondrocytes are adept at immune evasion as they do elicit an active response to allogenic chondrocytes and are capable of suppressing immune proliferation¹³. The risk of disease transmission or infection is possible with any allogenic transplantation. However, DeNovo NT® cartilage undergoes the same strict requirements for any transplantation, which include testing for known transmissible diseases for each donor as well as sterility testing for each set of DeNovo NT® that is ordered.

Prior to the use of DeNovo NT®, the treating physician must be aware of the cost of utilizing the chondrocytes. The current cost of 1 unit of DeNovo NT® graft costs approximately $4,000-$5.000. The nature of this procedure requires that the surgeon orders the correct amount of chondrocytes prior to in vivo evaluation of the lesion. Pre-operative MRI and plan films give some indication of the true character of the lesion; however, subtle aspects of the lesion may not be fully appreciated prior to full exposure. It is therefore possible to order too much DeNovo NT® graft, which is a significant monetary waste.

The use of DeNovo NT® requires an open arthrotomy, which, although a fairly common practice, is not without associated morbidity in comparison to arthroscopic procedures often performed in the knee. At this point there is no specific evidence to suggest that DeNovo NT® has superior outcomes to other arthroscopic procedures to address patellar cartilage defects. Thus, the surgeon must factor in the morbidity of the surgery itself in comparison to other known options when considering DeNovo NT®. Perhaps, similar to the evolution of the Use of DeNovo NT® in OCD lesions of the talus^15,16, techniques will develop that will allow the use of DeNovo NT® for patellar lesions arthroscopically, thus decreasing the morbidity associated with the open arthrotomy.

The current study indicates that use of DeNovo NT® is a potentially effective treatment for patellar cartilage defects. However, there are several limitations to this study. Firstly, this is a relatively small case series with retrospectively reviewed data. Thus, despite significant improvement in the overall KOOS score and improvements in all KOOS subscales, the study was underpowered and could not find a significant effect in the KOOS subscales. This is similar to the previous case series reported in the literature^5,18. However, a more powered study would likely indicate improvement of all KOOS subscales and other functional outcome measures. Also, the length of follow up is of short (average 8.2 months) and thus functional outcomes and potential complications cannot be fully determined. Although, a second look arthroscopy performed in one patient indicated full integration of the graft (Figure 2), we do not provide advanced imaging or histology in each patient that is suggestive of restoration of the articular surface.

Figure 2. Arthroscopic image obtained at secondary arthroscopy indicating integration of DeNovo NT® juvenile particulated cartilage.

The results of this study, similar to previous studies, indicate the potential advantages of DeNovo NT® for use in treatment of patellar cartilage defects. Further studies, with larger number of patient are required to fully address the effectiveness and safety of use of DeNovo NT® in patellar lesions. There is no clear superiority of one cartilage resurfacing procedure over another. We recommend Fulkerson osteotomy and cartilage resurfacing for central and medial patella lesions. Lateral patella lesions can be treated with osteotomy alone.

Conflict of interest statement:

Each author certifies that he has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.