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Arthroscopic treatment of post-traumatic knee chondral defects using microfractures and the Autologous Collagen-Induced Chondrogenesis (ACIC™) technique: a retrospective observational cohort study
, Alessandro Ivonea, Edoardo Bianchi Viscontia,b, Domenico Iovinellaa, Roberto Edoardo Vanellia
⁎Corresponding author: Ilaria Morelli. ilaria.morelli@asst-nordmilano.it
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Received: ,
Accepted: ,
This article was originally published by Reed Elsevier India Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.
Abstract
Abstract
This study aimed to evaluate return to sport and one-year clinical outcomes in young athletes with focal grade III–IV knee chondral lesions treated arthroscopically using the Autologous Collagen-Induced Chondrogenesis (ACIC™) technique, which combines microfractures with an atelocollagen scaffold stabilized by fibrin glue.
A retrospective cohort study was conducted on all consecutive patients undergoing arthroscopic microfractures with ACIC™. Inclusion criteria comprised monofocal ICRS III–IV knee chondral defects ≥1 cm2, young sports-active patients, and a minimum follow-up of one year. Patients with malalignment >5°, knee instability, inflammatory disease, BMI ≥30, or kissing lesions were excluded. Pain and function were assessed after injury and one year postoperatively. Sport level (Tegner Activity Scale) was compared before injury and at one year postoperatively.
Four patients met the inclusion criteria. Lesions were located on the femoral condyle (n = 3) or tibial plateau (n = 1), with a mean defect area of 1.8 ± 1 cm2. Three patients returned to their pre-injury level of sport at one year. No significant difference was observed between pre-injury and postoperative Tegner scores. Significant improvements were found in VAS pain (p = 0.004) and IKDC functional scores (p = 0.0009) after surgery. All patients reported to be highly satisfied with the surgery.
Arthroscopic ACIC™ demonstrated significant pain reduction, improved knee function, and a high rate of return to pre-injury sport level at one-year follow-up in young athletes with focal high-grade knee chondral lesions. Larger studies with long-term follow-up are needed to confirm durability and characterize cartilage repair quality.
III.
Keywords
ACIC
Autologous Collagen-Induced Chondrogenesis
CartiRegen®
Knee
Patient-reported outcomes
Return to sport
Chondral defects
1 Introduction
Chondral lesions of the knee are a common condition in adults, often resulting from trauma or degenerative changes. Literature indicates that these lesions may be present in up to 60 % of knee arthroscopies1,2. They often cause reduced sports participation and, in some cases, limitations in daily activities due to pain, swelling, and joint stiffness.
The regenerative ability of hyaline cartilage in adults is limited; therefore, medium-to high-grade lesions frequently require surgical treatment.3,4 As a result, they continue to pose a significant challenge for orthopedic surgeons.
Various cartilage repair techniques have been proposed, including stimulative methods (microfractures, drilling), cell-based chondrogenesis with mesenchymal stem cells, repair procedures (mosaicplasty, osteochondral allograft transplantation), tissue engineering with cultured cells, and acellular matrix-based cartilage regeneration.1,5,6 Among these, Autologous Collagen-Induced Chondrogenesis (ACIC) has shown highly favorable clinical and functional results.4,7–11 This one-stage arthroscopic procedure involves creating microfractures at the lesion to stimulate the proliferation and migration of mesenchymal stem cells from the bone marrow.12 These cells are then stabilized with a gel-like atelocollagen, which acts as a scaffold supporting their maturation and differentiation into hyaline-like cartilage.3,12
The type I atelocollagen used in the ACIC™ technique is derived from porcine skin after removing tissue-specific telopeptides, resulting in high purity and low antigenicity, ensuring safety for human use.3,12 When combined with fibrin glue, the atelocollagen forms a gel-like substance that helps stabilize the clot at the microfracture site.12
This study aims to assess the return to sports activity and functional outcomes in young athletes with focal grade III–IV chondral lesions, according to the International Cartilage Repair Society (ICRS) classification, treated arthroscopically with microfracture combined with an atelocollagen scaffold gel and fibrin glue.
2 Materials and methods
2.1 Study design
A retrospective observational cohort study was carried out, in accordance with the STROBE guidelines, including all consecutive patients treated with arthroscopic microfractures and the ACIC™ technique between October 2022 and September 2024 at our institution. The study was conducted in accordance with the Declaration of Helsinki. Ethical approval was waived under the local and national laws for this kind of study. All patients were informed of the possibility of future publications deriving from their treatment and gave their consent for anonymized data publication in any form.
Inclusion criteria were:•Monofocal knee chondral defects classified as ICRS III-IV,•Defect size ≥1 cm,•Minimum follow-up of ≥1 year,•Young, sports-active patients.
Exclusion criteria were:•Kissing chondral lesions,•Defect size <1 cm,•Knee malalignment exceeding 5° of varus or valgus,•Knee instability (ligamentous injury).•Body Mass Index≥30•Inflammatory joint disease
Preoperative and postoperative data, including Patient Reported Outcome Measures (PROMs), intraoperative findings, and postoperative clinical data, were retrieved from the institutional clinical software and entered into a dedicated database.
2.2 Outcomes
The clinical outcome was assessed by comparing knee pain levels after injury and one year after surgery using the Visual Analogue Scale (VAS). Functional knee status after the injury and one year after surgery was measured using the Italian-validated version of the International Knee Documentation Committee (IKDC) score.13 Return to sport was evaluated by comparing the level of sport activity before injury and one year after surgery using the Italian-validated version of the Tegner Activity Scale.14
2.3 Surgical technique
The procedure is performed in the operating room under spinal anesthesia, with the patient placed in the supine position. A pneumatic tourniquet and a leg holder with a post are employed to facilitate the procedure. The affected lower limb is prepared and draped in a sterile manner for knee arthroscopy. Through standard anterolateral and anteromedial parapatellar portals, the chondral defect is debrided and the cartilage surface regularized, obtaining shouldered borders. Microfractures are then performed using a chondral pick. Simultaneously, atelocollagen (CartiRegen, Joint Biomaterials, Joint Srl, Venice, Italy) is sterilely mixed with fibrin glue (Tisseel™, Baxter, Deerfield, IL, USA; or Evicel®, Ethicon, Johnson&Johnson, North Ryde, Australia).
Following evacuation of the intra-articular saline, the composite is applied to the defect under dry conditions, after CO2 intra-articular insufflation or air insufflation using a 50-mL syringe through the anteromedial parapatellar portal, under arthroscopic visualization. The knee is passively cycled several times to ensure optimal distribution of the mixture and to promote defect filling. Arthroscopic portals are closed using non-absorbable monofilament sutures.
2.4 Postoperative period
In the immediate postoperative period, the patient is allowed to walk with crutches without weight-bearing on the operated limb for 20 days, while full flexion and extension of the knee are permitted from the first postoperative day. Prophylaxis against venous thromboembolism is administered via subcutaneous enoxaparin sodium (4000 UI, once daily) for 20 days postoperatively. Isometric muscle strengthening and joint mobility physiotherapy begin immediately after surgery. After 20 days, gait re-education with assistive devices is initiated, with progressive weight-bearing as tolerated, based on pain in the operated limb. Rehabilitation protocols also address restoration of muscular strength and proprioception. Return to sport is permitted after 6 months. Postoperative follow-up evaluations are scheduled at 10 days, 20 days, 1 month, and at 3, 6, and 12 months after surgery. At the 12-month follow-up visit, patients completed the IKDC score, VAS, and Tegner Activity Scale questionnaires to assess the one-year outcomes objectively.
2.5 Statistical analysis
Descriptive statistics (mean and standard deviations) were calculated using Excel (Microsoft Excel for Mac, ©2025 Microsoft. Statistical analysis was performed using Prism 10 (© 1995–2025 Graphpad Software, LLC). Normality of data distributions (VAS, Tegner Activity Scale, and IKDC score) was assessed using the Shapiro-Wilk test. Pre-operative and post-operative values were compared using paired T-test for normally distributed variables and Wilcoxon signed-rank test for non-normally distributed variables.
3 Results
Four patients (three males and one female), with a mean age at the time of surgery of 26 ± 13.5 years, met the inclusion criteria and were ultimately included in this study. The chondral defects were located on the medial femoral condyle in two cases, and on the lateral femoral condyle and lateral tibial plateau in one case each. The mean defect area was 1.8 ± 1 cm2, with a mean diameter of 1.7 ± 0.6 cm. The patients’ clinical and demographic data are summarized in Table 1.
| Patient n° | Age at surgery | Gender | Defect location | Defect largest diameter (cm) and shape | Defect area (cm2) |
| 1 | 24 | Female | Lateral tibial plateau, right knee | 2 (circular) | 3.1 |
| 2 | 13 | Male | Lateral femoral condyle, left knee | 2 (ovoidal) | 1.6 |
| 3 | 45 | Male | Medial femoral condyle, left knee | 1 (circular) | 0.8 |
| 4 | 22 | Male | Medial femoral condyle, right knee | 1.5 (circular) | 1.8 |
| Mean ± SD | 26 ± 13.5 | 1.7 ± 0.6 | 1.8 ± 1 |
Three patients were engaged in competitive sports, and one in amateur-level sports, before injury. After surgery, all patients except one returned to the pre-injury level of sport. The Tegner Activity Scale values were non-normally distributed. The comparison between mean pre-injury and postoperative Tegner Activity Scale at 1-year follow-up showed no statistically significant difference. Sport activity level and Tegner Activity Scale are reported in Table 2.
| Patient n° | Pre-injury sport level | Postoperative sport level at 1-year follow-up | Pre-injury Tegner Activity Scale | Postoperative Tegner Activity Scale at 1-year follow-up | p-value (Wilcoxon signed-rank test) |
| 1 | Soccer (competitive level) | Soccer (competitive level) | 9 | 9 | |
| 2 | Soccer (competitive level) | Soccer (competitive level) | 9 | 9 | |
| 3 | Padel (amateur) | Padel (amateur) | 6 | 6 | |
| 4 | Soccer (competitive level) | Futsal (amateur) | 9 | 8 | |
| Mean ± SD | 8.3 ± 1.5 | 8 ± 1.4 | 0.317 |
VAS and IKDC score values (post-injury and at 1-year follow-up) were normally distributed. A statistically significant reduction in knee pain (p = 0.004) and improvement in function (p = 0.0009) were observed when comparing post-injury and 1-year postoperative VAS and IKDC scores. VAS and IKDC score values are reported in Table 3.
| Patient n° | Post-injury IKDC score | Postoperative IKDC score at 1-year follow-up | p-value (Paired t-test) | Post-injury VAS | Postoperative VAS at 1-year follow-up | p-value (Paired t-test) |
| 1 | 35 | 98 | 7 | 0 | ||
| 2 | 38 | 94 | 7 | 0 | ||
| 3 | 48 | 93 | 6 | 0 | ||
| 4 | 50 | 77 | 6 | 2 | ||
| Mean ± SD | 42.8 ± 7.4 | 90.5 ± 9.3 | 0.004 | 6.5 ± 0.6 | 0.5 ± 1 | 0.0009 |
All patients reported being very satisfied with this surgery at 1-year follow-up.
4 Discussion
Focal chondral lesions are a common pathological condition of the knee. In young athletes, they may result in prolonged absence from sport and, in some cases, in a downgrade in the patient's level of athletic performance.15 Several treatment techniques have been described in the literature. Bone marrow stimulation techniques (drilling, microfractures) have the advantages of very low cost and technical simplicity.16 However, their outcomes are generally inferior, as they primarily result in the formation of fibrous cartilage, which is biomechanically inferior to hyaline cartilage.16 Autologous chondrocyte implantation on a scaffold, while effective and currently considered the gold standard, is associated with significant drawbacks, including high costs, prolonged treatment times, and sometimes the need for two-stage open procedures.17 Osteochondral transplantation offers comparable efficacy, but its feasibility is limited by lesion size and location.18 Furthermore, they require an open approach, and potential safety issues exist when osteochondral allografts are used.19
The ACIC™ technique, introduced by Shetty and Kim in 2013, has been shown in the literature to be equally effective for the treatment of chondral defects.8,9 Thanks to its cost-effectiveness and the possibility of performing the procedure arthroscopically, ACIC™ represents an excellent compromise in terms of economic sustainability, procedural efficiency, and minimally invasive approach.10
Most of the studies published in the literature originate from the Shetty-Kim group, who analyzed the efficacy of the ACIC™ technique at a short and medium-term follow-up. Their early work in 2013 demonstrated the feasibility of combining microdrilling with an atelocollagen scaffold stabilized by fibrin glue on 10 patients, achieving significant improvement in Lysholm scores at 2-year follow-up and good cartilage quality in the MRI analysis performed after 1 year.9 The addition of MRI T2 mapping by Stelzeneder et al. confirmed that the repair tissue exhibited properties similar to native cartilage.7
Subsequent studies by Shetty et al. in 2016 and Kim et al. in 2020 confirmed the durability of these outcomes on a larger cohort of 30 patients at 4 and 6-year follow-up, with sustained improvements in KOOS, IKDC, and Lysholm scores and very good cartilage quality at MRI MOCART analysis. These data support the formation of mature, hyaline-like cartilage and stable functional recovery up to six years postoperatively.10,20
An independent study on 11 patients by Silva et al., in 2020, using an alternative collagen matrix, further validated the reproducibility of ACIC™ outcomes across materials and lesion types, using PROMs alone, without a MRI follow-up.8
The technique has also been applied to osteochondral lesions of the talus.
Volpi et al. reported an improvement in pain and ankle function in 5 patients with talar lesions treated with ACIC™, at short-term follow-up (6 months).4 Usuelli et al. reported a non-statistically significant clinical and functional improvement, with variable MRI outcomes on 9 patients at one-year follow-up.11
Previously published studies on the ACIC technique are summarized in Table 4.
| Authors and Year | N. of patients | Defect location | Defect size | Technique | Outcome measures | Follow-up | Results |
| Shetty et al., 2013a9 | 10 | Knee (6 patella, 5 MFC, 1 LFC, 2 throclea (4 patients with 2 lesions) | 2–8 cm2 | Microdrilling and ACIC™ (Coltrix™ atelocollagen 0.9 ml + Tisseel™ fibrinogen 1 ml + thrombin 0.1 ml (50IU) | MRI (MOCART score);PROMs: Lysholm score | MRI: 1 yearLysholm: 2 years | Mean MOCART: 70.4 ± 20.2Lysholm improvementb |
| Stelzeneder et al., 2013a7 | 10 | Knee (6 patella, 5 MFC, 1 LFC, 2 throclea (4 patients with 2 lesions) | 2–8 cm2 | Microdrilling and ACIC™ (Coltrix™ atelocollagen 0.9 ml + Tisseel™ fibrinogen 1 ml + thrombin 0.1 ml (50IU) | MRI (MOCART score, T2 mapping) | 1 year | Mean MOCART: 71.7 ± 21T2 mapping: repair cartilage similar to native cartilage |
| Volpi et al., 20144 | 5 | Talus | 2.5–4 cm2 | Microfractures and ACIC™ (Cartifill™ atelocollagen + fibrin glue, 1:1 ratio) | PROMs: AOFAS score, VAS, Tegner Activity Scale | 6 months | AOFAS and VAS improvementb, postoperative Tegner varied between patients |
| Shetty et al., 2016a20 | 30 | Knee (MFC, LFC, throclea, patella) | 2–8 cm2 | Microdrilling and ACIC™ (Coltrix™ atelocollagen 0.9 ml + Tisseel™ fibrinogen 1 ml + thrombin 0.1 ml (50IU) | MRI (MOCART score)PROMs: Lysholm, IKDC and KOOS scores | 4 years | Mean MOCART: 72Lysholm, IKDC, and KOOS improvementb |
| Usuelli et al., 201611 | 9 | Talus | >1.5 cm2 | Microfractures and ACIC™ (Cartifill™ atelocollagen + Tisseel™ fibrin glue, 1:1 ratio) | MRI (MOCART score)PROMs: AOFAS score, VAS | 1 year | Mean MOCART: 51AOFAS and VAS improvementb (non-statistically significant) |
| Kim et al., 2020a10 | 30 | Knee | 4.6 cm2 ± 2 | Microdrilling and ACIC™ (fibrin glue 1: thrombin 0.2: atelocollagen 0.8 ratio) | MRI (MOCART score, T2 mapping)PROMs: KOOS, IKDC, Lysholm scores | 6 years | Mean MOCART: 78.5T2 mapping: repair cartilage similar to native cartilage.KOOS, IKDC and Lysholm score statistically significant improvementb. |
| Silva et al., 20208 | 11 | Knee (8 MFC, 1 LFC, 2 throclea) | 0.5–3 cm | Microfractures and ACIC™ (Cartifill™ atelocollagen 0.9 ml + Tisseel™ fibrinogen 1 ml + thrombin 0.1 ml, 1:1 ratio) | PROMs: IKDC, SF-36, VAS | 2 years | IKDC, SF-36, VAS improvementb |
| Present study | 4 | Knee (2 MFC, 1 LFC, 1 lateral tibial plateau) | 1.8 ± 1 cm2 | Microfractures and ACIC™ (CartiRegen™ atelocollagen + fibrin glue Tisseel™/Evicel®, 1:1 ratio) | Tegner Activity Scale, IKDC, VAS | 1 year | IKDC and VAS improvementb, Tegner Activity Scale similar to pre-injury level |
This is the second independent study on the ACIC™ technique for knee chondral lesions. We analyzed the return to sport in patients with focal chondral lesions treated with the ACIC technique. All patients except one returned to their pre-injury level of sports activity after surgery, with a Tegner score at one year postoperatively comparable to the pre-injury level. A statistically significant reduction in pain and improvement in function (IKDC score) was observed when comparing post-injury VAS and IKDC values with those at one year after surgery.
This study has some limitations. First, the sample size is relatively small. Nevertheless, the differences between post-injury and postoperative patient-reported outcome measures were statistically significant. Furthermore, the follow-up period was limited to one year, and postoperative MRI was not performed to assess the radiological quality of the repair tissue.
Future independent studies on larger cohorts are needed to confirm the long-term durability of the hyaline-like cartilage produced by the ACIC™ technique, particularly in patients who return to sports at competitive levels.
5 Conclusions
The ACIC™ technique, performed by combining microfractures with atelocollagen (CartiRegen) mixed with fibrin glue, demonstrated a significant reduction in pain and improvement in function at one-year follow-up, allowing three out of four patients to return to their pre-injury level of sports activity. Further studies with long-term follow-up are needed to confirm the durability of the clinical benefit and the persistence of the hyaline-like cartilage produced, particularly in competitive athletes.
Informed consent
All patients included were informed of the possibility of future publications deriving from their treatment and gave their consent for anonymized data publication in any form (including unidentified images, open access publications, etc.).
CRediT authorship contribution statement
Conceptualization, G.G., I.M., A.I., R.E.V.; Methodology, G.G, I.M., R.E.V.; Validation, A.I., E.B.V., D.I.; Investigation, G.G., E.B.V., A.I., D.I., I.M.; Formal Analysis, G.G., I.M.; Writing – Original Draft, G.G., I.M; Writing - Review and Editing, G.G., I.M., A.I., D.I., E.B.V., R.E.V.; Visualization, G.G., I.M., A.I., D.I., E.B.V., R.E.V.; Supervision and Project Administration, R.E.V.
Authorship declaration
All the authors listed meet the authorship criteria according to the latest guidelines of the International Committee of Medical Journal Editors.
All the authors: 1) gave substantial contributions to the conception/design of the work; to the acquisition, analysis, and interpretation of data for the work; 2) Drafted the work or revised it critically for important intellectual content; 3) approved the final version to be published; 4) agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Ethical approval
All procedures reported in this study were in accordance with the ethical standards of our institutional and national research committee and with the Helsinki Declaration and its subsequent amendments. Ethical approval is waived under the local and national laws for this kind of study and for reporting anonymized and unidentified images and data.
Declaration of generative AI and AI-assisted technologies in the manuscript preparation process
During the preparation of this work the authors used Grammarly to proofread the manuscript language. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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