Aragonite-Based Scaffolds Are Effective Osteochondral Graft Substitutes for Osteochondral Defects of the Knee: A Systematic Review

Purpose

To evaluate the outcomes and complication profiles after the implantation of aragonite-based scaffold osteochondral substitutes for the treatment of osteochondral lesions of the knee.

Methods

Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we completed a comprehensive search of the PubMed, Embase, and Medline databases in January 2025 to obtain studies reporting on outcomes after implantation of an aragonite-based scaffold in patients with osteochondral defects of the knee. Clinical studies were assessed for patient-reported outcome measures, failure rates, and magnetic resonance imaging findings. Risk-of-bias assessment was performed and the Methodological Index for Non-randomized Studies (MINORS) criteria were applied to appraise study quality.

Results

Five studies were included for data analysis. In total, 526 patients with a mean age of 39.1 years (range, 31.6-42.0 years) were followed up for an average of 30.5 months (range, 12-78 months). Four studies evaluating Knee Injury and Osteoarthritis Outcome Scores reported mean improvements of 16.1 to 41.0 from preoperatively to final follow-up. Three studies reported improvements of 23.1 to 43 in International Knee Documentation Committee Subjective Knee Form scores. Failure, defined as any secondary intervention on the index knee, occurred in 0% to 13.6% of cases, and these rates were significantly lower than those for microfracture and arthroscopic debridement. Tapered scaffolds had lower failure rates than cylindrical designs (0% vs 8%-10.5%).

Conclusions

Aragonite-based scaffolds in the treatment of osteochondral lesions of the knee show improved patient-reported outcomes and low failure rates at mean follow-up durations ranging from 12 to 78 months.

Level of Evidence

Level IV, systematic review of Level I and IV studies.

Symptomatic articular cartilage lesions of the knee are relatively common, and at the time of arthroscopy, there is a 60% to 63% incidence of chondral lesions regardless of symptoms. ^, When conservative treatment is unsuccessful, surgical options include chondroplasty, microfracture, osteochondral autograft, osteochondral allograft (OCA), autologous chondrocyte implantation, and particulated juvenile cartilage allograft. For smaller lesions, depending on the size and amount of subchondral involvement, surgical treatments include chondroplasty, marrow stimulation, and osteochondral autograft transfer. ^, Marrow stimulation techniques, such as microfracture, have been reported to have poorer outcomes compared with cartilage repair procedures, and marrow stimulation procedures may also jeopardize the outcomes of any future salvage cartilage repair procedures because of the risk of bony overgrowth, which may occur in up to 60% of patients. Autologous cartilage implantation has shown good clinical results for chondral lesions with no subchondral bony involvement, but this technique requires a 2-stage procedure for cartilage biopsy followed by implantation. For deeper lesions involving subchondral bone, osteochondral autograft or allograft is typically required, with larger lesions requiring allograft, and these techniques have shown favorable outcomes with return-to-sport rates of up to 88%. Although OCA transplantation has been reported to have good outcomes with some advantages over some other procedures, including no donor-site morbidity, as well as the use of a 1-stage procedure and customizable implants, it does carry the risk of disease transmission and immune response from the host and is dependent on allograft availability.

Whereas the aforementioned treatments are commonly used for osteochondral lesions, cartilage substitutes have been developed to mitigate disadvantages such as donor-site morbidity, the need for a 2-stage procedure, the risk of disease transmission, and the requirement to have a fresh allograft available that has a limited shelf life. Recently, multiple studies have reported on the use of an aragonite-based scaffold (Agili-C; Smith & Nephew, Memphis, TN) for the treatment of chondral and osteochondral lesions. The aragonite-based scaffold is a cell-free biphasic osteochondral scaffold composed of inorganic calcium carbonate (aragonite) that received Food and Drug Administration approval for use in the United States in 2022, and a few clinical trials have shown promising results. ^,^,^,^,^,

The purpose of this systematic review was to evaluate the outcomes and complication profiles after the implantation of aragonite-based scaffold osteochondral substitutes for the treatment of osteochondral lesions of the knee. It was hypothesized that, across all available studies, the use of aragonite-based scaffold osteochondral substitutes for knee-based osteochondral lesions would be associated with improvements in patient-reported outcomes (PROs) with low complication rates.

Methods

Literature Search and Study Eligibility

This systematic review was registered in PROSPERO and was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A literature search of the PubMed, Scopus, Embase (Elsevier, Amsterdam, The Netherlands), and Medline (Ovid) databases was completed in January 2025 for articles discussing aragonite scaffolds used for the treatment of osteochondral defects of the knee. The following terms were searched in the keyword, title, and abstract fields: “aragonite scaffold,” “aragonite graft,” “Cartiheal,” “Agili-C,” “coral cartilage repair,” and “synthetic cartilage graft.” Filters applied included studies published in the past 10 years, written in English, and involving human subjects. After completion of the literature search, citations were cross-referenced to identify articles that may have been missed during the initial search.

Studies reporting clinical outcomes of aragonite-based scaffolds in the context of the treatment of knee chondral or osteochondral defects in patients 18 years or older were included. Exclusion criteria were technical reports, review studies, conference abstracts, editorial commentaries, case series with fewer than 3 patients, studies without full-text availability in the English language, studies with less than 12-month clinical follow-up, and studies without reported clinical outcomes. In addition, if multiple studies reported outcome data for the same population, the study with the shorter final follow-up was excluded. During the appraisal process, articles deemed at high risk of bias or of low or very low quality were excluded.

Screening and Included Variables

Two authors (J.D.M., N.W.) independently completed a full-text review. Disagreements during the screening process were resolved by the senior author (A.C.K.). A Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) diagram detailing the processes of study identification, selection, and screening is found in Figure 1 .

Image, AltText currently not available — Fig 1

To identify subgroups for analysis, results from eligible clinical studies were evaluated. Common variables of interest included the following: overall Knee Injury and Osteoarthritis Outcome Score (KOOS) and its subscales, proportion of KOOS responders (defined as a ≥30-point increase in the overall KOOS), International Knee Documentation Committee (IKDC) Subjective Knee Form (SKF) score, cartilage volume defect fill as determined on magnetic resonance imaging (MRI), and rate of failure (defined as the need for any secondary surgical intervention).

Study Appraisal

Risk of bias and publication quality were determined using tools appropriate for the design of the included studies. Randomized clinical trials were evaluated using the Cochrane Collaboration’s tool (RoB-2), and results were visualized using the robvis program ( Fig 2 ). ^, With the use of this tool, appraisal was completed in the following 5 domains: randomization, blinding, reporting of outcomes, measurement of outcomes, and selection of results. In each domain, trials were provided with a rating of “low,” “some concerns,” or “high” based on an algorithmic determination regarding concern for bias.

Observational, nonrandomized studies were evaluated using the Methodological Index for Non-randomized Studies (MINORS) scoring criteria. Details are presented in the [CR] ^, . Results from study appraisal of the included articles using the MINORS criteria are found in Table 1 . An overall assessment including study demographic characteristics, methodology, and appraisal scores is found in Table 2 .

Table 1

Breakdown of MINORS Scoring After Quality Appraisal of Included Observational, Nonrandomized Studies

	de Caro et al. (2024, Cartilage )	Kon et al. (2016, Injury )	Kon et al. (2021, AJSM)
MINORS criteria
1. Clearly stated aim	2	2	2
2. Inclusion of consecutive patients	2	2	2
3. Prospective collection of data	2	2	2
4. Endpoints appropriate to aim of study	2	2	2
5. Unbiased assessment of study endpoint	0	0	1
6. Follow-up period appropriate to aim of study	2	2	2
7. Loss to follow-up < 5%	1	2	1
8. Prospective calculation of study size	0	0	0
Additional MINORS criteria for comparative studies
9. Adequate control group	—	1	—
10. Contemporary groups	—	1	—
11. Baseline equivalence of groups	—	1	—
12. Adequate statistical analyses	—	2	—
Total MINORS score	11 of 16	17 of 24	12 of 16
Study quality	Moderate	Moderate	Moderate
Level of evidence	IV	IV	IV

NOTE. A score of 0 indicates not reported; 1, reported but inadequate; and 2, reported and adequate.

AJSM, American Journal of Sports Medicine ; MINORS, Methodological Index for Non-randomized Studies.

Table 2

Study Demographic Characteristics, Methodology, and Scoring

Authors	Year	Journal	Patients Receiving Aragonite-Based Scaffold Implant, n	Mean Follow-Up, mo	Mean Age, yr	Methodology/Design	Level of Evidence	Risk of Bias Assessment	MINORS Score
Altschuler et al.	2023	AJSM	167	24	42.0	Randomized controlled trial Arthroscopic debridement/microfracture as control group Power analysis completed	I	Some concerns	—
Conte et al.	2024	International Orthopaedics	164	48	41.8	Randomized controlled trial Arthroscopic debridement/microfracture as control group Power analysis completed	I	Some concerns	—
de Caro et al.	2024	Cartilage	12	78	34.4	Prospective case series No control group Outcomes presented for longer follow-up of population previously studied by Van Genechten et al.	IV	—	11 of 16
Kon et al.	2016	Injury	97	12	31.6	Prospective comparative cohort study with historical control group Compared tapered vs cylindrical scaffolds No power analysis completed	IV	—	17 of 24
Kon et al.	2021	AJSM	86	24	37.4	Prospective case series No control group	IV	—	12 of 16