Safety of three different product doses in autologous chondrocyte implantation: results of a prospective, randomised, controlled trial

Abstract

BackgroundThis study was conducted to assess the efficacy and safety of the three dose levels of the three-dimensional autologous chondrocyte implantation product chondrosphere® in the treatment of cartilage defects (4–10 cm2) of knee joints. We hereby report the safety results for a 36-month post-treatment observation period.MethodsThis was a prospective phase II trial with a clinical intervention comprising biopsy for culturing spheroids and their subsequent administration (level of evidence: I). Patients’ knee defects were investigated by arthroscopy, and a cartilage biopsy was taken for culturing. Patients were randomised, on a single-blind basis, to treatment at the dose levels 3–7 (low), 10–30 (medium) or 40–70 (high) spheroids per square centimetre. Assessment (adverse events, vital signs, electrocardiography, physical examination, concomitant medication and laboratory values) took place 1.5, 3, 6, 12, 24 and 36 months after chondrocyte implantation.ResultsSeventy-five patients were included and 73 treated. The incidence of adverse events, of patients with adverse events and of patients with treatment-related adverse events showed no relevant difference between the treatment groups. There were no fatal adverse events, no adverse events led to premature withdrawal from the trial and none led to permanent sequelae. Two patients experienced serious adverse events considered related to the study treatment: arthralgia 2–3 years after implantation and chondropathy 1 and 2 years after implantation.ConclusionsThe treatment with chondrosphere® was generally well tolerated. No relationship was detected between any safety criteria and the dose level: Differences between the dose groups in the incidence of any adverse events, and in numbers of patients with treatment-related adverse events, were insubstantial.Trial registrationclinicaltrials.gov, NCT01225575.

Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue‐engineered cartilage

“…In many use cases, high initial load bearing capabilities are not necessarily required. For example, established clinical applications in cartilage repair make use of chondrocytes, which are encapsulated in fibrin within a polyglycol acid carrier fleece or are applied as spheroids, both posing only minimal initial mechanical stability. The load‐bearing features of the transplant develop in vivo promoted by environmental factors such as mechanical force, oxygen tension, and synovial fluid constituents .…”

Autologous Chondrocyte Implantation with Chondrosphere for Treating Articular Cartilage Defects in the Knee: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

“…However, the lack of a control group was deemed to reduce its value. Interim effectiveness results (at 12 months) together with safety data (at 36 months) have been published [9,10] while final effectiveness and safety results (at four years) were presented in confidence by the Company. Four-year results showed no important difference amongst the three groups based on the Knee Injury and Osteoarthritis Score (KOOS) score which assesses pain, symptoms, activities of daily living, sport and recreational activities (on a scale of 0 to 100, where 100 is best).…”

Challenges in Fabrication of Tissue-Engineered Cartilage with Correct Cellular Colonization and Extracellular Matrix Assembly

“…The aggregates can be formed by either rotating a cell suspension until they gather and form a mass [ 115 ] or by seeding the cells into a cell culture insert [ 113 ] or agarose wells [ 116 , 117 ]. The aggregate cultures have been used to create cartilage microtissues [ 118 ], and at least one commercial application exists as well [ 119 ].…”