The Incidence and Clinical Relevance of Graft Hypertrophy After Matrix-Based Autologous Chondrocyte Implantation

Abstract

Background: Graft hypertrophy is the most common complication of periosteal autologous chondrocyte implantation (p-ACI). Purpose: The aim of this prospective study was to analyze the development, the incidence rate, and the persistence of graft hypertrophy after matrix-based autologous chondrocyte implantation (mb-ACI) in the knee joint within a 2-year postoperative course. Study Design: Case series; Level of evidence, 4. Methods: Between 2004 and 2007, a total of 41 patients with 44 isolated cartilage defects of the knee were treated with the mb-ACI technique. The mean age of the patients was 35.8 years (standard deviation [SD], 11.3 years), and the mean body mass index was 25.9 (SD, 4.2; range, 19-35.3). The cartilage defects were arthroscopically classified as Outerbridge grades III and IV. The mean area of the cartilage defect measured 6.14 cm2 (SD, 2.3 cm2). Postoperative clinical and magnetic resonance imaging (MRI) examinations were conducted at 3, 6, 12, and 24 months to analyze the incidence and course of the graft. Results: Graft hypertrophy developed in 25% of the patients treated with mb-ACI within a postoperative course of 1 year; 16% of the patients developed hypertrophy grade 2, and 9% developed hypertrophy grade 1. Graft hypertrophy occurred primarily in the first 12 months and regressed in most cases within 2 years. The International Knee Documentation Committee (IKDC) and visual analog scale (VAS) scores improved during the postoperative follow-up time of 2 years. There was no difference between the clinical results regarding the IKDC and VAS pain scores and the presence of graft hypertrophy. Conclusion: The mb-ACI technique does not lead to graft hypertrophy requiring treatment as opposed to classic p-ACI. The frequency of occurrence of graft hypertrophy after p-ACI and mb-ACI is comparable. Graft hypertrophy can be considered as a temporary excessive growth of regenerative cartilage tissue rather than a true graft hypertrophy. It is therefore usually not a persistent or systematic complication in the treatment of circumscribed cartilage defects with mb-ACI.

Evaluation and analysis of graft hypertrophy by means of arthroscopy, biochemical MRI and osteochondral biopsies in a patient following autologous chondrocyte implantation for treatment of a full-thickness-cartilage defect of the knee

“…While the majority of studies examining the presence of hypertrophy only at a defined point in time and mostly describe a tendency to regress after 2 years [14,23], the present case is in display of a first occurrence of hypertrophy after 18 months and a further increase over time.…”

“…Second, a complete autologous cell product (without the use of a biodegradable membrane) was used for ACI for which hypertrophy has not been described so far [16,27]. In general, the risk for transplant hypertrophy has been associated with the use of autologous periosteum and in the rare number of cases in which transplant hypertrophy occurs with third-generation ACI products [6,18,23], it has been described being asymptomatic and declining over time without need for re-intervention [14,23]. For this reason, conservative treatment has been chosen.…”

“…Although the incidence of graft hypertrophy seems closely to be associated with the use of autologous periosteum as described as ''first generation ACI'', graft hypertrophy has also been described in patients following second or even third-generation ACI proving that it is not exclusively related to the use of autologous periosteum [5,6,18,23]. This observation also makes it improbable that periosteum alone is responsible for the formation of graft hypertrophy.…”

Autologous chondrocyte implantation for cartilage repair: current perspectives

“…35 The rate of hypertrophy of the transplant or periosteum was reduced by the matrix-guided technique. 35,36 Compared to other reconstructive therapy options for cartilage defects, like microfracturing or OAT, the MACT shows the best quality of the regenerated tissue. 37 Especially for full-thickness cartilage defects larger than 4 cm 2 , the MACT is the recommended therapy in literature.…”

Hydrogels and bioreactors for cartilage research and functional tissue engineering

“…In some cases such as NeoCart ® , external biomimetic stimuli in form of hydrostatic pressure, hypoxia, and direct perfusion are applied by specialised bioreactors to improve construct maturation. [412][413][414] Besides the two-stage therapies listed in Table 6.1, a number of single-stage treatments are currently under investigation. Among these, two hydrogel-based therapies, GelrinC and ChonDux™, have been applied in clinical cartilage lesion repair.…”