Characteristics of repair tissue in second-look and third-look biopsies from patients treated with engineered cartilage: relationship to symptomatology and time after implantation

Abstract

IntroductionThe present study established characteristics of tissue regrowth in patients suffering knee lesions treated with grafts of autologous chondrocytes grown on three-dimensional hyaluronic acid biomaterials.MethodsThis multicentred study involved a second-look arthroscopy/biopsy, 5 to 33 months post implant (n = 63). Seven patients allowed a third-look biopsy, three of which were performed 18 months post implant. Characteristics of tissues were histologically and histochemically evaluated. The remaining bone stubs were evaluated for cartilage/bone integration. For data analysis, biopsies were further divided into those obtained from postoperative symptomatic patients (n = 41) or from asymptomatic patients (n = 22).ResultsThe percentage of hyaline regenerated tissues was significantly greater in biopsies obtained after, versus within, 18 months of implantation. Differences were also observed between symptomatic and asymptomatic patients: reparative tissues taken from symptomatic patients 18 months after grafting were mainly fibrocartilage or mixed (hyaline–fibrocartilage) tissue, while tissues taken from asymptomatic patients were hyaline cartilage in 83% of biopsies. In a small group of asymptomatic patients (n = 3), second-look and third-look biopsies taken 18 months after surgery confirmed maturation of the newly formed tissue over time. Cartilage maturation occurred from the inner regions of the graft, in contact with subchondral bone, towards the periphery of the implant.ConclusionsThe study indicates that, in asymptomatic patients after chondrocyte implantation, regenerated tissue undergoes a process of maturation that in the majority of cases takes longer than 18 months for completion and leads to hyaline tissue and not fibrous cartilage. Persistence of symptoms might reflect the presence of a nonhyaline cartilage repair tissue.

A mathematical model of cartilage regeneration after cell therapy

“…The first aspect is the time frame of matrix production in our model. The time frame of 18 months for a defect to reach full maturation after chondrocyte implantation corresponds with results from a recent clinical study of patients treated with autologous chondrocytes seeded in a hyaluronan-based polymer (Brun et al (2008)). The analysis of 70 biopsies from 63 patients in that study, taken between 5 months and 333 months after surgery, demonstrated that cartilage regeneration is a slow process taking around 18 months.…”

Bioreactor based engineering of large-scale human cartilage grafts for joint resurfacing

“…At the time of its implantation, the Hyalograft-C graft contains chondrocytes attached to the Hyaff-11 mesh fibers, but little to no extracellular matrix, and thus, maturation of the implanted construct (biochemically and mechanically) occurs within the repair site [17], typically taking more than 18 months [18]. While a graft with negligible mechanical properties may be sufficient for filling focal defects, in which the surrounding healthy native cartilage may be sufficient to support joint loading, a graft for resurfacing the lateral or medial condyle would likely need to be at a more advanced stage of maturation to provide a higher degree of functionality.…”

A case study: Glycosaminoglycan profiles of autologous chondrocyte implantation (ACI) tissue improve as the tissue matures

“…Furthermore, CS chains were significantly shorter in 12 month ACI repair tissue 8 . Many studies have reported on maturation of chondrocytes in pellets 31 and cartilage like tissue in scaffolds 32 but very few studies have reported on tissue maturation within a cartilage defect 11,12,29 .…”

“…Basic histological studies of ACI biopsies indicate that repair tissue matures slowly [11][12][13] . Further detailed studies are necessary to fully assess the molecular characteristics of the tissue as it matures over time.…”