International Journal of Orthopedics (IJO)
ISSN: 2643-2692 | Vol. 7, Issue 1, 2026, pp. 40-47

Autologous Chondrocyte Implantation for Knee Cartilage Defects: Five-Year Follow-Up

Keller J1, Byrne C2, Iliev R3

1Department of Orthopaedic Surgery, University of Heidelberg, Heidelberg, Germany
2Department of Sports Medicine, University of Galway, Galway, Ireland
3Department of Cell and Tissue Engineering, Medical University of Sofia, Sofia, Bulgaria
DOI: 10.5281/zenodo.22327994 | Published: 2026-08-22 | Article page and PDF

Abstract

Background: Autologous chondrocyte implantation (ACI) has evolved through three technical generations for treating

symptomatic articular cartilage defects of the knee, yet its comparative durability against microfracture and osteochondral

grafting remains debated. Objective: To synthesise evidence on ACI's generational evolution and five-year and longer functional outcomes, durability, andreturn to sport relative to alternative cartilage repair techniques.Methods: Narrative review of randomised trials, long-term cohort studies, and meta-analyses.Findings: Randomised trials show ACI and matrix-induced ACI (MACI) achieve functional outcomes equal to or better thanmicrofracture at two to five years, with superior durability beyond five years, particularly for larger defects; MACI reoperationrates at 10-17 years (9.0%) are markedly lower than pooled first/second-generation ACI failure rates at 11.4 years (18%).Conclusions: ACI/MACI provides durable, generation-dependent improvement in knee function, favouring larger defects and younger patients, though comparative superiority over osteochondral grafting remains procedure- and lesion-specific.

Keywords: Autologous chondrocyte implantation; Matrix-induced autologous chondrocyte implantation; Microfracture; Knee cartilage defect; Osteochondral autograft transplantation

Abstract

Background: Autologous chondrocyte implantation (ACI) has evolved through three technical generations for treating symptomatic articular cartilage defects of the knee, yet its comparative durability against microfracture and osteochondral grafting remains debated. Objective: To synthesise evidence on ACI's generational evolution and five-year and longer functional outcomes, durability, and return to sport relative to alternative cartilage repair techniques. Methods: Narrative review of randomised trials, long-term cohort studies, and meta-analyses. Findings: Randomised trials show ACI and matrix-induced ACI (MACI) achieve functional outcomes equal to or better than microfracture at two to five years, with superior durability beyond five years, particularly for larger defects; MACI reoperation rates at 10-17 years (9.0%) are markedly lower than pooled first/second-generation ACI failure rates at 11.4 years (18%). Conclusions: ACI/MACI provides durable, generation-dependent improvement in knee function, favouring larger defects and younger patients, though comparative superiority over osteochondral grafting remains procedure- and lesion-specific.

Keywords: autologous chondrocyte implantation; matrix-induced autologous chondrocyte implantation; microfracture; knee cartilage defect; osteochondral autograft transplantation

Introduction

Symptomatic focal articular cartilage defects of the knee are a common cause of pain and dysfunction in young, active patients and, if untreated, are associated with progression toward early osteoarthritis. Such lesions are frequently encountered incidentally during knee arthroscopy and, when symptomatic and full-thickness, rarely heal spontaneously because hyaline cartilage is avascular and has limited intrinsic capacity for repair. A spectrum of restorative procedures has therefore been developed, ranging from marrow-stimulation techniques such as microfracture, which recruits marrow-derived mesenchymal cells to form a mechanically inferior fibrocartilage repair, to cell-based and osteochondral grafting strategies intended to restore a more hyaline-like repair tissue. Autologous chondrocyte implantation, first described three decades ago as a two-stage procedure in which cultured autologous chondrocytes are re-implanted beneath a periosteal patch, was the first clinically validated cell-based cartilage repair technique and reported good early results in the distal femur [1]. Since that original description, ACI has undergone substantial technical evolution, and a large body of randomised and long-term cohort evidence has accumulated regarding its comparative outcomes against microfracture and osteochondral autograft and allograft transplantation.

This review synthesises the published literature on ACI and its matrix-induced derivative (MACI) for symptomatic knee cartilage defects: the generational evolution of the technique, head-to-head trial evidence against microfracture, comparative outcomes against osteochondral autograft/allograft transplantation, patient-reported and functional outcomes at five years and beyond (Knee injury and Osteoarthritis Outcome Score [KOOS], Lysholm, International Knee Documentation Committee [IKDC]), graft durability and failure, and return to sport. It is a narrative synthesis rather than a report of a single institutional series.

Generational Evolution of ACI Technique

First-generation ACI relies on a periosteal flap sutured over the defect to contain injected chondrocytes, a technique effective but complicated by periosteal hypertrophy requiring reoperation in a meaningful minority of patients [2]. Second-generation ACI replaced the periosteal patch with a porcine collagen membrane, reducing hypertrophy-related reoperation while preserving the biological principle of a contained cell suspension [3]. Third-generation, matrix-induced ACI (MACI) seeds chondrocytes directly onto a collagen scaffold prior to implantation, permitting arthroscopic or mini-open delivery, more homogeneous cell distribution, and shorter operative time [3]. A systematic review of level I and II evidence found second- and third-generation ACI produced equivalent or superior clinical outcomes to first-generation ACI with fewer graft-related complications, supporting matrix-based techniques as the current standard [3]. Consistent with this trajectory, an early prospective randomised comparison of first-generation, periosteum-covered ACI against collagen-covered ACI found equivalent clinical and arthroscopic outcomes at two years but a markedly lower rate of graft hypertrophy requiring reoperation with the collagen-covered technique, providing direct trial-level support for abandoning the periosteal patch [4]. A related marrow-stimulation-based one-stage alternative, autologous matrix-induced chondrogenesis (AMIC), combines microfracture with an overlying collagen membrane and has been proposed as a simpler single-stage option for small-to-moderate defects, though it remains a distinct technique from true chondrocyte implantation [5].

ACI versus Microfracture: Randomised Trial Evidence

The most extensively studied comparator for ACI is microfracture. The original Norwegian multicentre trial randomised 80 patients with femoral condyle defects and found no significant difference between ACI and microfracture in functional outcome at two years [6]. Subsequent characterized chondrocyte implantation (CCI) trials found better structural repair by histomorphometry with cell-based treatment despite similar clinical scores at one to two years [7], and by five years CCI treatment of defects larger than 4 cm produced superior clinical outcomes to microfracture, particularly when performed early after symptom onset [8]. The SUMMIT trial, comparing MACI directly with microfracture, found significantly greater KOOS improvement with MACI at two years [9], an advantage that was maintained and, in the pain and activities-of-daily-living domains, grew significantly larger by five years (Table 1) [10]. A Korean randomised trial of costal chondrocyte-derived pellet-type ACI similarly demonstrated significantly greater improvement in International Knee Documentation Committee and visual analogue pain scores than microfracture at two years [11], with the clinical advantage sustained at five-year follow-up [12]. Meta-analytic pooling across these and other trials confirms that ACI/MACI produces functional outcomes at least equivalent to, and for larger or long-standing defects better than, microfracture, with the treatment gap widening over time as microfracture-treated fibrocartilage repair tissue degrades [13,14].

Table 1: Selected randomised trials comparing ACI/MACI with microfracture for symptomatic knee cartilage defects [6,7,8,9,10,11,12]. Study Comparison Follow-up Key outcome
Table 1: Selected randomised trials comparing ACI/MACI with microfracture for symptomatic knee cartilage defects [6,7,8,9,10,11,12]. Study Comparison Follow-up Key outcome

Study Comparison Follow-up Key outcome

Yoon 2024 Pellet-type ACI vs 5 years Clinical advantage microfracture of ACI sustained

ACI versus Osteochondral Autograft and Allograft Transplantation

Osteochondral autograft transplantation (OAT) and osteochondral allograft (OCA) transplantation are the principal alternatives for larger or osteochondral lesions unsuitable for isolated ACI. A meta-analysis restricted to larger cartilage defects found no significant difference between OAT and ACI in Lysholm or IKDC outcomes, though OAT carried a higher rate of donor-site-related complications [15]. A broader systematic review and meta-analysis spanning ACI, MACI, OAT, and OCA concluded that all four techniques meaningfully improved knee function and pain, with technique selection best guided by defect size, containment, and bone involvement rather than an expected difference in patient-reported outcome [16]. In the patellofemoral joint specifically, a comparative cohort at a mean follow-up of five years found comparable clinical and functional outcomes between OCA and ACI, supporting either as a reasonable option in this technically demanding compartment [17]. A network meta-analysis of randomised trials across microfracture, AMIC, OAT, and ACI likewise found ACI among the most effective options for larger defects at intermediate- and long-term follow-up, while differences between grafting techniques were less pronounced for smaller lesions [18]. An insurance-database comparison of ACI and OCA found a higher two-year reoperation rate after ACI, reflecting its staged, biologically driven maturation process, without a corresponding difference in overall complication burden [19].

Five-Year and Longer Functional Outcomes

Across trials and cohorts, ACI/MACI produces clinically meaningful, durable improvement in KOOS, Lysholm, and IKDC scores that is generally sustained from two years through five years and beyond [10,12]. A systematic review pooling long-term ACI cohorts at a mean follow-up of 11.4 years found substantial mean improvements from baseline (Lysholm +24.9 points, IKDC +16.5 points, Tegner +1.1 points), with an 82% overall long-term success rate but a pooled reoperation rate of 37% [20]. Mid- to long-term follow-up of first-generation ACI similarly demonstrated maintained functional gains, although larger and trochlear defects showed relatively greater score deterioration over time [21,22]. A long-term cohort followed for 10 to 20 years (mean 12.8 years) after ACI found that clinical improvement was maintained in most patients, with better outcomes in those treated for isolated defects than for multiple lesions [23]. These findings collectively indicate that ACI's functional benefit is not merely an early post-operative phenomenon but persists over a clinically important time horizon (Table 2).

Table 2: Long-term functional and durability outcomes after ACI reported in cohort and systematic-review literature [20,22,23,21,25]. Study Population Follow-up Key finding
Table 2: Long-term functional and durability outcomes after ACI reported in cohort and systematic-review literature [20,22,23,21,25]. Study Population Follow-up Key finding

Graft Durability, Failure, and Reoperation

Long-term durability differs meaningfully by generation and defect characteristics. In the pooled 11.4-year systematic review, defects larger than 4.5 cm carried a substantially higher failure rate (23.8%) and reoperation rate (51.6%) than smaller defects (8.7% and 10.8%, respectively), identifying defect size as the dominant predictor of durability [20]. At 14 to 15 years, the original Norwegian RCT cohort found treatment failure in 17 of approximately 40 ACI-treated knees compared with 13 of approximately 40 microfracture-treated knees, with more total knee arthroplasties in the ACI group (6 versus 3), alongside radiographic osteoarthritis in roughly half of surviving patients in both arms (Figure 1) [24]. By contrast, a systematic review of MACI cohorts with minimum 10-year (up to 17-year) follow-up reported a considerably lower reoperation rate of 9.0% and progression to total knee arthroplasty in only 7.4% of patients, alongside durable patient-reported outcome improvement and satisfactory MRI defect fill (Figure 2) [25]. This apparent improvement in long-term durability with matrix-based technique, though drawn from non-randomised comparisons across different eras and case mixes, is consistent with the mechanistic rationale for second- and third-generation ACI and merits confirmation in direct

Figure 1: Treatment failure and conversion to total knee arthroplasty at 14-15 years in the original Norwegian randomised trial comparing ACI with microfracture (17 versus 13 failures and 6 versus 3 arthroplasties among approximately 40 patients per arm) [24].
Figure 1: Treatment failure and conversion to total knee arthroplasty at 14-15 years in the original Norwegian randomised trial comparing ACI with microfracture (17 versus 13 failures and 6 versus 3 arthroplasties among approximately 40 patients per arm) [24].
Figure 2: Pooled long-term reoperation rate after pooled first/second-generation ACI at a mean of 11.4 years (37%) [20] versus matrix-induced ACI (MACI) at a minimum of 10 years, up to 17 years (9.0%) [25].
Figure 2: Pooled long-term reoperation rate after pooled first/second-generation ACI at a mean of 11.4 years (37%) [20] versus matrix-induced ACI (MACI) at a minimum of 10 years, up to 17 years (9.0%) [25].

Return to Sport

Return to athletic activity is a key outcome for the young, active population typically treated with ACI. A systematic review of return to sport after cartilage repair found that a majority of athletes returned to some level of sport after ACI, though rates of return to the pre-injury competitive level were lower and more variable, particularly in pivoting and high-impact sports [26]. A more recent systematic review of contemporary cartilage restoration studies reported high overall return-to-sport rates across current cartilage procedures, including ACI/MACI, with return more likely after smaller defects, shorter symptom duration, and younger age at surgery [27]. Across the literature, time to return to sport after ACI is longer than after microfracture, typically 9 to 12 months, reflecting the staged biological maturation of the graft, but the resulting repair tissue may better tolerate high-impact loading over the long term. Structured, criterion-based rehabilitation protocols, rather than fixed timelines alone, are increasingly used to individualise return-to-sport clearance and may further improve both safety and consistency of reporting across future studies.

Conclusion

Three decades after its introduction, ACI has matured from a periosteum-based first-generation procedure into matrix-induced techniques with improved surgical handling and a growing long-term evidence base. Randomised trials demonstrate outcomes equivalent or superior to microfracture, particularly for larger defects and with longer follow-up, and comparative cohorts suggest broadly similar functional results to osteochondral autograft and allograft transplantation, with technique choice best individualised to defect size, containment, and patient factors. Long-term durability appears to have improved across ACI generations, and most patients return to some level of sporting activity, though pre-injury competitive return remains inconsistent. Continued long-term randomised follow-up, particularly comparing matrix-induced ACI directly against osteochondral grafting, is needed to refine indications further.

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