A novel aragonite-based scaffold for osteochondral regeneration: early experience on human implants and technical developments

doi:10.1016/S0020-1383(16)30836-1

Injury

Volume 47, Supplement 6, December 2016, Pages S27-S32

https://doi.org/10.1016/S0020-1383(16)30836-1 Get rights and content

Abstract

Introduction

Chondral and osteochondral lesions represent a debilitating disease. Untreated lesions remain a risk factor for more extensive joint damage. The objective of this clinical study is to evaluate safety and early results of an aragonite-based scaffold used for osteochondral unit repair, by analysing both clinical outcome and MRI results, as well as the benefits of the procedure optimization through novel tapered shaped implants.

Methods

A crystalline aragonite bi-phasic scaffold was implanted in patients affected by focal chondral-osteochondral knee lesions of the condyle and trochlea. Twenty-one patients (17 men, 4 women with a mean age of 31.0 ± 8.6 years) without severe OA received tapered shaped implants for the treatment of 2.5 ±1.7 cm² sized defects. The control group consisted of 76 patients selected according to the same criteria from a database of patients who previously underwent implantation of cylindrical-shaped implants.

The clinical outcome of all patients was evaluated with the IKDC subjective score, the Lysholm score, and all 5 KOOS subscales administered preoperatively and at 6 and 12 months after surgery, while MRI evaluation was performed at the 12 month follow-up.

Results

A statistically significant improvement in all clinical scores was documented both in the tapered implants and the cylindrical group. No difference could be detected in the comparison between the improvement obtained with the two implant types, neither in the clinical nor in imaging evaluations. A difference could be detected instead in terms of revision rate, which was lower in the tapered implant group with no implant removal – 0% vs 8/76–10.5% failures in the cylindrical implants.

Conclusions

This study highlighted both safety and potential of a novel aragonite-based scaffold for the treatment of chondral and osteochondral lesions in humans. A tapered shape relative to the cylindrical shaped implant design, improved the scaffold's safety profile. Tapered scaffolds maintain the clinical improvement observed in cylindrical implants while reducing the postoperative risk of revision surgery. This aragonite-based implant was associated with a significant clinical improvement at the 12 month follow-up. Moreover, MRI findings revealed graft integration with good bone and cartilage formation.

Introduction

Chondral and osteochondral lesions represent a debilitating disease, which if left untreated would progress to more extensive joint damage eventually leading to the development of osteoarthritis [1]. Clinical and research activities are ongoing in an effort to improve outcomes and over the years different surgical techniques have been suggested [2]. Among these, regenerative scaffold-based procedures are emerging as a potential therapeutic option, with an increasing number of publications every year on in vitro, preclinical animal studies and clinical applications [3, 4], but none has shown tissue healing with biomechanical properties that match the physiological condition.

Lately, the awareness of the involvement of subchondral bone in many of these lesions, resulted in the development of cell-free treatment strategies focused on the entire osteochondral unit [5, 6, 7], and currently heterogeneous scaffolds have been proposed that combine distinct but integrated layers corresponding to the cartilage and bone regions to regenerate both components of the osteochondral unit to restore the articular surface [8, 9, 10, 11].

Most scaffolds attempt to regenerate the articular cartilage by implantation of soft biomaterials to act as a cartilage surrogate that is supposed to allow surface reconstitution. Recent literature described a different approach to target osteochondral regeneration: an aragonite-based bi-phasic scaffold, which showed promise in the preclinical model [12, 13]. To date, only a preliminary report in humans has been published, with positive results at 24 months for the treatment of a patient affected by a chronic posttraumatic cartilage lesion of the knee [14]. However, prior to wide range clinical application, it is important to document both safety and feasibility of this procedure, which is based on the implant of a scaffold relying on a press-fit fixation. Considering that sufficient attachment and graft stability in the early period are essential for the successful outcome of any technique, since an insufficient graft fixation may facilitate the detachment of the transplanted biomaterial and lead to treatment failure [15], we focused on the stability evaluation of this procedure, which has been first developed with cylindrical implants and recently optimized through a new shape for tapered implants. To document the early postoperative adherence rate in humans, invasive approaches are not appropriate due to patient safety concerns and disruption of the primary stability. Thus, magnetic resonance imaging (MRI) is useful as a non-invasive technique for the analysis of the morphological status of cartilage defects and the repair tissue throughout the postoperative period [16, 17]. In the current work, we evaluated both early clinical results as well as MRI imaging of a pilot group of patients undergoing implantation of the tapered aragonite-based scaffold with the objective to compare the results of treatment to a historical control of patients who previously underwent cylindrical scaffold implantation.

Section snippets

Scaffold characteristics and implantation procedure

The implant (Agili-C™, CartiHeal, Israel) consists of a natural crystalline aragonite, derived from corals, to which hyaluronic acid (HA) is added. The natural aragonite, possess a nano-rough structure as well as interconnecting porosity that allows to stimulate cell adhesion and proliferation as well as matrix production [18]. A square grid pattern of 2 mm deep drilled channels is made in the top part, using Bungard CCD, a CNC drilling and routing machine and an appropriate drill-bit as

Results

A statistically significant improvement in all clinical scores was documented. In particular, in the tapered implant group the IKDC subjective score increased from 36.5 ± 14.2 to 58.9 ± 18.5 at 6 months and 63.2 ±18.0 at 12 months (P <0.005) (Figure 2). Similarly, the Lysholm score increased from 54.8 ± 18.5 to 70.9 ± 16.5 at 6 months and 75.6 ± 17.2 at to 12 months (P < 0.005) (Figure 3). An increase was also recorded in all KOOS subscales (Table 1). MRI evaluation performed in 19/21 patients

Discussion

Biological based therapies for the treatment of bone and cartilage lesions have been evolving as a result of all the advances made in regenerative medicine [20, 21, 22, 23, 24, 25, 26].

The main finding of this study is that implantation of the aragonite-based scaffold allowed to obtain a significant clinical improvement. The improvement following implantation of the scaffold was documented by both MRI imaging and clinical results. While efficacy is similar with both designs, safety is increased

Conflict of interest

E. Kon, D. Robinson, P. Verdonk, M. Drobnic, J.M. Patrascu, O. Dulic, G. Gavrilovic are paid consultants, G. Filardo is a paid presenter for Cartiheal Ltd.

Acknowledgments

E. Pignotti for the statistical analysis.

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