The primary finding of this study was the significant association of previous surgeries and female sex with an increased risk of reoperation following ACI for focal articular cartilage lesions of the knee joint. Patients with more than two previous surgeries had nearly twice the risk of undergoing reoperation following ACI, while female patients had roughly a 1.5-fold increased risk compared to male patients. Additionally, reoperation was associated with significantly worse KOOS at all follow-ups, including baseline. Furthermore, these patients were less likely to surpass the MCID at the 24-month follow-up.

The overall prevalence of reoperations (patients with at least one reoperation) in our cohort was 17.9%, which is lower than the recently reported 30.4% by Anigwe et al. and may be attributable to the shorter follow-up period in our study (2.2 ± 1.5 vs. 4.8 ± 3.3 years in Anigwe et al.), and the exclusive use of third-generation ACI in our cohort [1]. Anigwe et al. also demonstrated a significant decrease of reoperations for ACI performed after 2017 [1]. Harris et al. reported a similar reoperation rate of 33% in a systematic review, primarily including patients who underwent first-generation ACI [11]. Niethammer et al. reported a revision rate of 20.4% in a series of third-generation ACI with a minimum follow-up of 2 years [17], consistent with our study, although we reported all reoperations rather than revisions. Conversely, a systematic review from 2016 reported lower reoperation rates compared to our findings, with a pooled rate of 5% for patients undergoing reoperation at 2–5 years follow-up [26]. Furthermore, a recently published 9-year follow-up study of patients undergoing ACI reported a very low revision surgery rate of 7% [6]. This variability in reoperation rates underscores the need for further investigation. While we acknowledge the potential for an attrition bias due to a higher loss to follow-up in patients undergoing reoperations, our findings are consistent with previous studies [6, 11, 16, 20, 26].

The most frequently performed types of reoperations in our study were lysis of adhesions, chondroplasty, and meniscectomy. These findings are similar to those reported by Anigwe et al., who identified chondroplasty, meniscectomy and microfracture among the top three reoperation types [1]. Harris et al. also reported lysis of adhesions among the most frequently performed reoperations for arthrotomy-based ACI, along with chondroplasty (“graft debridement”) and manipulation under anesthesia [11]. However, it is worth noting that lysis of adhesions was predominantly reported in cohorts undergoing first-generation ACI. In our study, “lysis of adhesions” does not necessarily imply a distinct diagnosis of arthrofibrosis but could also refer to an arthroscopic debridement of minor scar tissue or partial synovectomy in case of persisting pain or mechanical symptoms following ACI.

The unfavorable effect of female sex on cartilage repair outcomes has been consistently documented in the literature [1, 8,9,10, 13,14,15]. Our findings align with these reports. Jungmann et al. reported an overall odds ratio of 1.7 for female patients regarding reoperation following ACI [13]. Filardo et al. observed worse clinical outcomes in female patients, although this effect was attenuated in a matched analysis considering different lesion patterns and causes of injury [9]. Kreuz et al. found the worst clinical outcomes in female patients with patellar lesions, despite men having, on average, larger patellar lesions [14]. The authors hypothesized that the inferior outcome scores in women might be attributable to insufficient proprioception and imbalances in muscle forces, and lower isokinetic strength, as demonstrated in an earlier study [15]. Faber et al. highlighted gender-specific discrepancies in terms of patient baseline characteristics, showing that women were older than men at the time of cartilage repair, had more previous surgeries and a longer symptom duration [8].

To elaborate on the interdependence of female sex and associated parameters, we conducted an analysis of covariance and assessed multicollinearity in our regression model. We found that the correlation coefficients between female sex and the other parameters were generally weak, with the highest coefficient observed between female sex and lesion localization (r = 0.16). Interestingly, the positive coefficient suggested that female sex was associated with a higher prevalence of tibio-femoral lesions, contrary to previous findings [8, 15]. The multicollinearity analysis showed an R2 value of 0.404 for female sex, indicating that 40.4% of the variability could be explained by the other variables in our model. In essence, this parameter displayed an intermediate association with the remaining variables. Given these findins and previous data, it is evident that female sex is typically associated with other baseline patient and lesion characteristics that are routinely recorded. However, our data also suggest that there may be additional gender-related differences yet to be investigated specifically.

The significant impact of previous surgeries on the risk of reoperation and worse KOOS following ACI aligns with existing literature [13, 25]. Furthermore, we demonstrated that this risk increases with the number of previous procedures. While the hazard ratio (HR) for 1–2 previous surgeries was approximately 1.5, having more than 2 previous procedures raised the HR to almost 2. These patients also failed to surpass the MCID of the KOOS subscores of pain and quality of life (QoL). Notably, a history of previous CR procedures is of particular concern, as reported by Seiferth et al. [25].

Our study also identified higher patient age, female sex, and a history of more than two previous surgeries as significantly associated with an increased risk of conversion to arthroplasty, consistent with the findings of Anigwe et al. [1]. The HR for patient age indicated a 7% increase in the risk of conversion arthroplasty per year, suggesting that a patient at 50 years had approximately twice the risk of a patient at 40 years for undergoing conversion arthroplasty following ACI. Female patients had over a threefold increased risk, while patients with more than 2 previous surgeries had an over fivefold increased risk of conversion to arthroplasty. The cox proportional-hazards model demonstrated a strong model fit for conversion to arthroplasty (R2 = 0.810, 95% CI [0.704, 0.916], p < 0.001), indicating that the risk of conversion arthroplasty could be accurately predicted based on patient age, sex, and history of previous surgeries.

In summary, this study, one of the largest reporting on reoperation rates and associated clinical findings following ACI, identified an increased risk of reoperation in female patients and patients with previous surgeries, which was linked to poorer clinical outcomes and a failure to surpass the MCID in most KOOS subscores. These findings have important implications for patient selection and managing patient expectations when scheduling ACI.

Several limitations should be acknowledged. The number of reoperations in our study may be subject to an attrition bias if there was a discrepancy in drop-out-rates between patients with and without reoperations. Additionally, as data on the type of reoperation were patient-reported via free-text entries, the exact type of reoperation was sometimes unclear and then categorized as “not specified”. Moreover, the patient-reported data carries the risk of underreporting. The cox proportional-hazards model for reoperation exhibited a weak model fit, suggesting limited accuracy in predicting reoperation risk based on the available parameters. Finally, our study included patients undergoing different types of CR and lesion localizations (tibio-femoral and patello-femoral), which should be considered when interpreting the data.

Reoperation and the failure to attain clinically relevant improvement following ACI of the knee are frustrating for both patients and physicians as the procedure requires two surgeries and an extensive rehabilitation protocol. Consequently, identifying patients at risk of reoperation and unfavorable clinical outcomes is paramount. The findings of the present study aid in streamlining this identification process by providing valuable insights into the implications of various baseline parameters.