MRI and clinical evaluation of collagen-covered autologous chondrocyte implantation (CACI) at two years

Abstract

We present our experience with the collagen-covered autologous chondrocyte implantation (CACI) technique. Thirty two implantations were performed in 31 patients. Clinical outcome was measured using the KOOS score and the 6-minute walk test, as well as an MRI scoring protocol (75% of patients had a complete data set for MRI follow-up) to describe the repair tissue generated by CACI. We have also correlated our MRI results with our clinical outcome. To the authors knowledge there are no comparative studies of MRI and clinical outcome following CACI in the current literature.

Patients demonstrated an increased walk distance that improved significantly from 3 months to 24 months postoperatively (p < 0.05). Analysis of the KOOS results demonstrated a significant (p < 0.05) improvement in four of the five subscales from 3 months to 24 months after CACI, with the most substantial gains made in the first 12 months. Patients demonstrated an increased MRI outcome score over time that improved significantly from 3 months to 24 months postoperatively (p < 0.05). We observed an 8% incidence of hypertrophic growth following CACI. We report one partial graft failure, defined by clinical, MRI and histological evaluation, at the one year time point. In contrast to the current literature we report no incidence of manipulation under anesthesia (MUA) following CACI.

This research demonstrates that autologous chondrocytes implanted under a type I/III collagen patch regenerates a functional infill material, and as a result of this procedure, patients experienced improved knee function and MRI scores. Whilst our results indicated a statistically significant relationship between the MRI and functional outcome following CACI, MRI cannot be used as surrogate measure of functional outcome following CACI, since the degree of association was only low to moderate. That is, functional outcome following CACI cannot be predicted by the morphological MRI assessment of the repair tissue at the post-surgery time points to 24 months.

Introduction

The concept of autologous chondrocyte implantation (ACI) began almost four decades ago [1], but only recently has the technique become a viable therapeutic option [2], [3], [4]. The first evidence supporting ACI came from animal studies by Peterson et al. [2]. This work led to human trials and subsequently, ACI using periosteal membrane (PACI) has become a well-established technique for the treatment of articular cartilage defects, with evidence of improved joint function and formation of hyaline or hyaline-like cartilage [5], [6], [7], [8], [9], [10]. The PACI has a number of short-comings, namely, the requirement for a large surgical incision, peripheral graft hypertrophy [11], [23], graft delamination [11], [12], [13], and potential ectopic calcification of the periosteal patch [12], [14]. Postoperatively, it has been documented that a clinically significant percentage of patients (20–36%) present with symptomatic “catching” of the knee joint due to hypertrophic graft edges, leading to the need for revision arthroscopy [15], [16].

Complications associated with the use of periosteum in the ACI procedure have stimulated the search for an alternative scaffold for the containment of implanted chondrocytes. According to Geistlich Biomaterials [17], the use of a type I/III collagen membrane (CACI) instead of periosteum to seal the cartilage defect is a better choice, and this membrane has been used extensively in dental and maxillofacial surgery since 1980. Recently, several studies have been published evaluating the CACI procedure [7], [16], [18], [19], [20], [21], [22] by clinical and arthroscopic assessment. Authors of these studies concluded that CACI produces favorable clinical and histological results [7], [18], [19], [20], [21], [22] which are at least comparable to PACI [16]. This paper reports non-invasive MRI in conjunction with routine clinical assessment to evaluate the outcome of CACI with a minimum of 2 year follow-up. To the authors’ knowledge, this study provides the most comprehensive MRI evaluation of CACI to date and is the first to correlate MRI scores with functional outcome measures following CACI. The study provides novel insight into the morphological progression of the regenerative tissue produced following CACI through the use of the latest MRI evaluation parameters as recommended by the literature. The results of this study complement the currently available clinical and histological information on CACI, with MRI assessment of the cartilage repair, a better understanding of the outcome of ACI with a collagen membrane is afforded.

In the present study, we have evaluated the CACI graft by MRI assessment, as well as the function of the grafted joint following surgery, in order to establish whether the CACI procedure may produce a potentially durable repair tissue. We postulate that the use of the type I/III collagen membrane would address the issue of graft hypertrophy that is associated with using a periosteal membrane and thus, CACI would provide a better capacity to facilitate cartilage regeneration compared to historical PACI data. Furthermore, it is our intention to demonstrate that early mobilisation via continuous passive motion (CPM) following CACI is safe and leads to a lower incidence of postoperative knee stiffness and subsequent manipulation under anaesthetic (MAU) than the current practice of immobilisation in plaster that is currently advocated in the literature.