Rehabilitation of the Knee After Autologous Matrix-Induced Chondrogenesis: A Systematic Review of Rehabilitation Protocols and Clinical and Radiological Outcomes

Abstract

Background:

Autologous matrix-induced chondrogenesis (AMIC) is an effective treatment for focal chondral knee lesions. Rehabilitation optimizes the environment for cartilage healing while avoiding deleterious effects to the repair site.

Purpose:

To evaluate rehabilitation protocols after AMIC and its effect on clinical and radiological outcomes.

Study Design:

Scoping review; Level of evidence, 4.

Methods:

Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the authors conducted a systematic search of the PubMed, Embase, Scopus, and Cochrane Library databases on April 30, 2025, using key search terms including “AMIC,”“knee,” and their synonyms. Outcomes assessed included the International Knee Documentation Committee (IKDC) score, visual analog scale (VAS) score, Lysholm score, and magnetic resonance imaging (MRI) findings. Descriptive synthesis of the data from 8 studies was conducted.

Results:

Eight studies were included, representing 258 patients (259 knees) with isolated AMIC. All chondral lesions were International Cartilage Regeneration & Joint Preservation Society grade 3 or 4 (mean defect size range, 2.6-3.7 cm²). There were 7 and 8 rehabilitation regimens available for condylar and patellofemoral lesions, respectively. Commencement of full weightbearing (FWB) varied from immediately to 10 weeks postoperatively. Four of 7 rehabilitation protocols for condylar lesions utilized progressive weightbearing (starting with partial weightbearing after surgery), permitting FWB at 4 to 10 weeks (mean, 7.5 weeks; median, 8 weeks), unrestricted range of motion (ROM) at 6 weeks (mean and median), jogging at 6 months (mean and median), and sports at 4 to 18 months (mean and median, 11 months) after surgery. Three of the 8 rehabilitation protocols for patellofemoral lesions permitted FWB immediately postoperatively, with unrestricted ROM at 28 to 56 days (mean, 38 days; median, 30 days) and sports at 4 to 6 months (mean and median, 5 months) after surgery. IKDC, VAS, and Lysholm scores and MRI findings generally improved in all studies at follow-up as compared with preoperative scores and MRI findings.

Conclusion:

This review demonstrated that rehabilitation protocols varied according to the location of the lesion, with a general trend of earlier weightbearing for patellofemoral lesions, in comparison with earlier ROM for condylar lesions. The postoperative clinical outcome and MRI findings are similar with both protocols, suggesting that this approach of customizing the ROM and weightbearing components in the rehabilitation protocol to the lesion site plays a role in the positive outcome.

Keywords

knee autologous matrix-induced chondrogenesis rehabilitation articular cartilage

Focal chondral lesions of the knee are found in up to 60% of patients undergoing knee arthroscopy^12,18 and are known to cause significant pain and functional impairment to patients.²³ Articular cartilage is a complex tissue designed to withstand tensional and shear stresses under mechanical load, primarily through the properties of collagen, which optimize load-bearing function.² However, as cartilage ages, there is a decrease in chondrocyte activity, which functions to maintain cartilage homeostasis.^10,45 Coupled with its avascular nature, articular cartilage has a poor regenerative capability, limited to regeneration with fibrous cartilage, which is biochemically and biomechanically inferior to native hyaline cartilage.^11,33

Microfracture is a marrow stimulation technique that was introduced by Steadman et al⁴⁷ in the 1990s, in which the calcified subchondral bone/cartilage border is perforated, leading to release of mesenchymal stem cells and development of fibrous cartilage.⁴⁸ A limitation of microfracture is that mesenchymal stem cells and growth factors are released into the joint rather than being contained at the cartilage defect. Furthermore, the newly formed clot may not be mechanically stable and therefore unable to withstand shear forces.¹³ Autologous matrix-induced chondrogenesis (AMIC), first introduced by Benthien and Behrens,⁵ is a 1-step procedure that builds on microfracture, combining it with fixation of a biological scaffold within the chondral defect. This matrix adds mechanical stability to the blood clot while allowing for vascular ingrowth and differentiation of mesenchymal stem cells into cartilage with hyaline-like characteristics.^31,42,54 AMIC is an effective treatment for focal chondral defects of the knee, with superior clinical outcomes when compared with microfracture.^29,38

After articular cartilage repair, rehabilitation serves to optimize the environment for cartilage healing while avoiding deleterious effects to the repair site.⁴⁰ Controlled movement and intermittent loading of the joint creates a pumping action to deliver nutrients and remove waste from the articular cartilage, and a gradual progression has been shown to stimulate matrix production and improve the tissue's mechanical properties.^10,52 Conversely, unloading and immobilization have been shown to have deleterious effects on cartilage healing.^4,27 However, an overly aggressive approach may risk damaging subchondral bone integrity and displacement of the collagen matrix.⁷ This creates a challenging dilemma for the surgeon and therapist when formulating a rehabilitation regimen after AMIC. Authors have suggested varying regimens, suggesting that there is currently no consensus on the optimal regimen.⁶ To the best of our knowledge, there is currently no systematic review or evidence-based guideline on the optimal rehabilitation regimen after AMIC. Hence, we performed a systematic review to explore current practice in postoperative rehabilitation regimens and its effect on clinical and radiographic outcomes. We hypothesize that rehabilitation regimens should be tailored according to its lesion characteristics to optimize outcomes.

Methods

Search Strategy

Four databases (PubMed, Embase, Scopus, and Cochrane Library) were systematically searched for articles published between January 1, 2010, and April 30, 2025, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, without language restrictions. The search strategy consisted of search terms involving “autologous matrix-induced chondrogenesis,”“AMIC,”“knee,”“patellofemoral joint,”“patella,” and “articular cartilage.” The complete search strategy is included in Supplementary Table S1. References of included articles were also searched for any relevant articles that met the inclusion criteria of the study.

The results of these searches were merged into Endnote, where the duplicates were removed. The remaining records were screened by title and abstract independently by 2 reviewers (J.Y. and J.J.W.) in accordance with the predetermined inclusion and exclusion criteria. After identification of potentially relevant studies from abstract screening, full-text articles were retrieved. Two reviewers (J.Y. and J.J.W.) independently screened the full texts and reasons for exclusion were recorded.

Inclusion and Exclusion Criteria

The inclusion criteria were studies that focused on International Cartilage Regeneration & Joint Preservation Society (ICRS) grade 3 or 4 AMIC in the knee, with a reported rehabilitation protocol. Studies with the following criteria were excluded: technical notes, systematic reviews, case reports, non–English-language articles, study population <18 years of age, duration of follow-up <2 years, insufficient detail on rehabilitation regimen, presence of concomitant procedures, and duplicate patient cohorts.

Data Extraction

The following variables were extracted from the studies by 2 independent reviewers (J.Y. and J.J.W.) using a standardized data collection form. Any discrepancies were resolved by a third reviewer (S.Y.J.L.). Study characteristics including the study design, sample size, duration of follow-up, and demographic data were extracted. Surgical data such as lesion location and severity, type of surgery, and rehabilitation protocol including progression of weightbearing were extracted. Because of the heterogeneity of the outcome measures in the studies, the data from the 4 most commonly used outcome measures were extracted: International Knee Documentation Committee (IKDC) score, visual analog scale (VAS) score, Lysholm score, and magnetic resonance imaging (MRI) findings.

Methodology Assessment

The Newcastle-Ottawa Scale (NOS) was used to assess methodology quality and risk of bias for observational studies.⁴⁶ A star system is used, whereby the overall score ranges from 0 to 9 stars, with 7 to 9 stars considered low risk of bias, 4 to 6 stars considered unclear risk of bias, and ≤3 stars considered high risk of bias.

The risk of bias of randomized controlled trials was assessed using Version 2.0 of the Cochrane Risk-of-Bias Tool for Randomized Trials (RoB 2.0).⁴⁹ RoB 2.0 evaluates 5 domains as being at low risk of bias, high risk of bias, or having some concerns: randomization process, deviations from intended interventions, missing outcome data, measurement of outcomes, and selection of the reported result.

Two reviewers (J.Y. and J.J.W.) independently assessed the included full texts using the NOS and RoB 2.0, with discrepancies resolved by a third reviewer (S.Y.J.L.).

Statistical Analysis

A descriptive synthesis of the rehabilitation protocols was conducted. Because of the heterogeneity of the data, meta-analysis of the data was not possible.

Results

The electronic search strategy retrieved 509 potentially relevant articles (Figure 1). After deduplication, 273 articles were screened by title and abstract, of which 33 articles were sought for full-text eligibility screening. Of the 31 articles assessed for eligibility through full-text screening, 23 were excluded based on the criteria detailed in Figure 1. Finally, 8 articles were included in the subsequent data extraction and descriptive analysis.^{1,3,8,28,37,41,43,51}

Figure 1.

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart. AMIC, autologous matrix-induced chondrogenesis.

Study Characteristics

The study characteristics are detailed in Appendix Table A1 (available in the online version of this article). A total of 258 patients (259 knees) treated by AMIC were included in the review. One patient underwent AMIC for chondral lesions in bilateral knees,²⁸ and the remainder underwent AMIC for unilateral chondral lesions. All studies had a minimum follow-up duration of 2 years. Inclusion and exclusion criterion are detailed in Appendix Table A1 (available online).

Methodology Assessment

Results of the NOS for methodology quality assessment are summarized in Table 1. The 6 observational studies were assessed to have low risk of bias. Results of the RoB 2.0 are summarized in Table 2. The 2 randomized controlled trials were assessed to have high risk of bias.

Table 1

Newcastle-Ottawa Scale for Observational Studies

Lead Author (Year)	Selection	Comparability	Outcome	Total Stars	Risk of Bias
Schiavone Panni (2018)⁴³	4	0	3	7	Low
Schagemann (2018)⁴¹	4	0	3	7	Low
Bertho (2018)⁸	4	0	3	7	Low
Migliorini (2021)³⁷	4	0	3	7	Low
Bąkowski (2022)³	4	2	3	9	Low
Joshi Jubert (2025)²⁸	4	0	3	7	Low

Table 2

RoB 2.0 for Randomized Controlled Trials ^a

Lead Author (Year)	Randomization Process	Bias Due to Deviations From Intended Interventions	Bias Due to Missing Data	Bias in Measurement of Outcomes	Bias in Selection of Reported Result	Overall
Anders (2013)¹	Low risk	High risk	Low risk	High risk	Low risk	High risk of bias
Volz (2017)⁵¹	Low risk	High risk	Low risk	High risk	Low risk	High risk of bias

RoB 2.0, Version 2.0 of the Cochrane Risk-of-Bias Tool for Randomized Trials.

Surgical Technique

The majority of the studies (7/8)^{1,3,8,28,37,43,51} utilized a mini-arthrotomy approach, while the remaining study⁴¹ utilized both mini-arthrotomy and arthroscopic approaches. The majority of studies (6/8)^{3,8,28,37,43,51} used a drill, while the remaining studies utilized an awl.^1,41 The majority of the studies (5/8)^{3,28,37,41,43} secured the matrix with tissue glue, while the remaining studies used tissue glue or suture fixation methods.^1,8,51

Chondral Lesion Characteristics

All chondral lesions were ICRS grade 3 or 4, with the mean defect size ranging from 2.6 to 3.7 cm². The majority of lesions (76/149) were located at the medial femoral condyle. The other locations included the lateral femoral condyle (33/149), patella (30/149), trochlear groove (9/149), and lateral tibial plateau (1/149) in descending numbers.

Rehabilitation Regimens

The rehabilitation regimens varied widely between studies (summarized in Appendix Tables A2 and A3, available online). There were 13 rehabilitation regimens available, the majority of which were tailored to the location of the lesion (condylar vs patellofemoral). Six^{3,8,28,41,43,51} were specific to patellofemoral lesions, 5^1,8,41,43,51 were specific to condylar lesions, and 2^3,37 were generic to both patellofemoral and condylar lesions. The majority of studies (Anders et al,¹ Volz et al,⁵¹ Schiavone Panni et al,⁴³ Schagemann et al,⁴¹ Bertho et al,⁸ and Joshi Jubert et al²⁸) differentiated the rehabilitation protocols according to the location of the lesion, between patellofemoral and condylar, whereas Bąkowski et al³ and Migliorini et al³⁷ used generic rehabilitation protocols for both patellofemoral and condylar lesions.

Weightbearing

The progression of weightbearing varied from immediately postoperatively to restriction of full weightbearing (FWB) up to 10 weeks. Weightbearing protocols utilized were categorized into the following: delayed weightbearing (starting with nonweightbearing), progressive weightbearing (starting with partial weightbearing), and immediate weightbearing (starting with FWB as tolerated).

Weightbearing: Condylar Lesion

There were 7 rehabilitation regimens for condylar lesions (Appendix Table A2, available online), and 4 of 7^8,37,41,51 were progressive weightbearing protocols. The mean postoperative duration to allow FWB was 7.5 weeks (median, 8 weeks). Jogging and sports were allowed at 6 months (mean and median) and 11 months (mean and median) respectively, after surgery.

Delayed weightbearing protocols for condylar lesions were utilized in 2 studies.^1,3 The duration of nonweightbearing was 2.5 weeks (mean and median). Partial weightbearing was allowed at 3.5 weeks (mean and median). FWB was allowed at approximately 2 months (mean and median, 8.5 weeks) postoperatively. Return to both jogging and sports was at 6 months (mean and median) postoperatively.

One study⁴³ reported immediate weightbearing for condylar lesions. Heavy work activity was allowed at 3 months, and sports were allowed at 6 months postoperatively. The study reported 21 lesions >2 cm², ICRS grade 4, and located at the medial femoral condyle (n = 11), lateral femoral condyle (n = 3), trochlea (n = 6), and patella (n = 1).

Weightbearing: Patellofemoral Lesion

Three of the 8 rehabilitation regimens^8,41,43 reported for patellofemoral lesions utilized immediate weightbearing protocols. Sports were allowed at 5 months (mean and median) postoperatively.

A progressive weightbearing protocol was adopted in 3 studies^28,37,51 with FWB at 8 weeks (mean and median) postoperatively. Jogging and sports were allowed at 6 (mean and median) and 15 (mean and median) months postoperatively, respectively.

A delayed weightbearing protocol was adopted in 2 studies.^1,3 The duration of nonweightbearing was 17.5 days (mean and median). Partial weightbearing was allowed at 3.5 weeks (mean and median) and FWB at 8.5 weeks (mean and median) postoperatively. Jogging and sports were allowed at 9 (mean and median) and 18 (mean and median) months postoperatively, respectively.

Range of Motion

Range of Motion: Condylar Lesion

Unrestricted range of motion (ROM) was permitted postoperatively at 30 days in the immediate weightbearing group, 6 weeks (mean and median) in the progressive weightbearing group, and 8 weeks (mean and median) in the delayed weightbearing group.

ROM: Patellofemoral Lesion

Unrestricted ROM was permitted postoperatively at a mean of 38 days (median, 30 days) in the immediate weightbearing group, 6 weeks (mean and median) in the progressive weightbearing group, and 8 weeks (mean and median) in the delayed weightbearing group.

Strengthening and Adjuncts

Physical exercises commonly commence with isometric strengthening of the quadriceps and proprioceptive exercises. Aquatic therapy was also utilized in early stages of rehabilitation in several studies. Various adjuncts such as continuous passive motion, electrotherapy, adjustable angle orthosis, and cold therapy were also utilized to facilitate rehabilitation regimens.

Outcomes

Various outcome measures were reported and are summarized in Table 3.

Table 3

Outcomes ^a

Lead Author (Year)	IKDC Score ^b		VAS Score ^b		Lysholm Score ^b		MRI Findings
	Preop	Postop	Preop	Postop	Preop	Postop	Postop
Anders (2013)¹	NR		NR		NR		At 1 y: 14 patients showed a defect filling of two-thirds or more At 2 y: complete integration was seen in 3 patients in the microfracture group, 8 patients in the sutured AMIC group, and 11 patients in the glued AMIC group
Volz (2017)⁵¹	NR		46 ± 20 (glued), 54 ± 19 (sutured)	15 ± 13 (glued), 16 ± 15 (sutured)	NR		At 1 y: 35-50% of patients had a defect filling of two-thirds or more; complete integration could be observed in 15-30% of patients in the different groups At 2 y: defect filling was more complete in the AMIC-treated groups, where at least 60% of patients had a defect filling of more than two-thirds At 5 y: defect filling was the lowest in the microfracture group, vs both AMIC-treated groups
Schiavone Panni (2018)⁴³	31.7 ± 8.9	80.6 ± 5.3	NR		38.8 ± 12.4	72.6 ± 19.5 (P < .05)	At 7 y: reduction of defect area and subchondral edema in 14 (66.6%) patients
Schagemann (2018)⁴¹	NR		5.18 ± 1.53	1.48 ± 1.5 (P < .005)	49.9 ± 15	81 ± 14.5 (P < .005)	NR
Bertho (2018)⁸	48	74	5.5	2.7	NR		NR
Migliorini (2021)³⁷	NR	75.9 ± 24.6	NR	2.5 ± 2.1	NR	71.2 ± 4.3	At 40 mo: MOCART 70 ± 19.4
Bąkowski (2022)³	42 ± 14	78 ± 14	NR		70 ± 11	90 ± 7	NR
Joshi Jubert (2025)²⁸	NR		8 ± 0.8 (6-9)	3.8 ± 2.3 (0-8)	NR		At 5 y: complete integration into adjacent cartilage in 8 (61.5%); complete filling of cartilage defect in 7 (53.9%)

AMIC, autologous matrix-induced chondrogenesis; IKDC, International Knee Documentation Committee; MOCART, magnetic resonance observation of cartilage repair tissue; MRI, magnetic resonance imaging; NR, not reported; postop, postoperatively; preop, preoperatively; VAS, visual analog scale.

Scores are reported as mean, mean ± SD, or mean ± SD (range).

Postoperative MRI was the most commonly reported outcome measure, reported in 5 studies.^{1,28,37,43,51} MRI was performed at varying intervals postoperatively, ranging from 1 to 7 years. The magnetic resonance observation of cartilage repair tissue (MOCART) score was reported in only 1 study.³⁷ All studies reported improvement in defect filling in most patients by the latest follow-up. There was reported defect filling, but incomplete, as early as 1 year after surgery. Joshi Jubert et al²⁸ reported complete filling in 53.9% at 5 years, and Schiavone Panni et al⁴³ reported reduction in defect area at 7 years. Volz et al⁵¹ reported that defect filling was the lowest in the microfracture group in comparison with the other 2 groups (AMIC) at 5 years. Integration was complete in 3 of 28 patients at 2 years (Anders et al¹) and in 8 of 13 (61.5%) knees (Joshi Jubert et al²⁸) at 5 years.

IKDC was reported in 4 studies,^3,8,37,43 with overall improvement from a score of 31.7 to 42 preoperatively to a score of 75.9 to 80.6 postoperatively. The most significant improvement in IKDC was observed in Schiavone Panni et al,⁴³ from 31.7 to 80.6.

Five studies^{8,28,37,41,51} reported VAS score, with overall improvement from scores of 4.6 to 8 preoperatively to scores of 1.48 to 3.8 postoperatively. The most significant improvement in VAS score, from 8 to 3.8, was reported by Joshi Jubert et al.²⁸

The Lysholm score was utilized in 4 studies,^3,37,41,43 with improvement from scores of 38 to 70 preoperatively to scores of 71.2 to 90 postoperatively reported. The most significant improvement, from 38.8 to 72.6, was observed in Schiavone Panni et al.⁴³

Discussion

The major findings of our study demonstrated that immediate weightbearing protocols were utilized in 3 of the 8 rehabilitation regimens for patellofemoral lesions,^8,41,43 as compared with only 1 of the 8 rehabilitation regimens for condylar rehabilitation protocols.⁴³ Four of the 7 rehabilitation regimens for condylar lesions^8,37,41,51 utilized progressive weightbearing protocols, with a mean postoperative duration of 7.5 weeks to allow FWB.

The rehabilitation regimens in the current review are designed according to the location of the lesion, namely, condylar and patellofemoral lesions. Despite the significant variations in weightbearing and ROM components, there is no clear advantage of one rehabilitation regimen over the next, and the patients gained significant improvement in clinical and radiological outcomes. There appears to be a general trend in that the progression in weightbearing is faster for patellofemoral lesions, while a faster progression in ROM is seen in condylar lesions.

Among patellofemoral lesions, 3 of 8 studies commenced FWB immediately postoperatively, within the ROM restriction of 0° to 40° for the first 8 weeks. This ROM restriction reconciles with the biomechanics of the patellofemoral joint. As the knee flexes, the patella engages the articulating surface of the trochlea groove at approximately 20° to 30° of knee flexion.²⁶ From 30° to 90°, the patellofemoral joint stress and contact area of the patellofemoral joint gradually increase.⁵³ Bearing this in mind, during the initial phase of cartilage healing, where the matrix is vulnerable to shear and compressive forces, ROM restriction at 0° to 30° is consistent with no significant patellofemoral articulation, to avoid a deleterious effect on the matrix. The degree of restriction may also be verified intraoperatively, by assessing the amount of flexion permissible before the lesion comes into articulation. Weightbearing via the tibiofemoral joint with this ROM restriction is unlikely to pose a negative effect to the repair in the patellofemoral joint.

In condylar lesions, the progression of weightbearing is undertaken more conservatively, with 4 of 7 studies starting partial weightbearing immediately postoperatively, within the ROM restriction of 0° to 90°. Unlike the patellofemoral joint, the tibiofemoral articulation has a relatively constant articulation throughout the arc of knee flexion, with femoral rollback in deeper flexion shifting the articulation point posteriorly on the tibial plateaus.^24,35 Hence, condylar lesion repair sites are inevitably subjected to more uniform compression and shear forces through the gait cycle. It is important to minimize the load and shear stress on the condylar repair during ROM, and thus it is safer to limit initial weightbearing for condylar lesions to partial weightbearing.

There were no patients with reported bipolar lesions for analysis in the included studies. Six of the included studies excluded bipolar lesions from treatment. This is potentially a group with poorer outcomes as compared with isolated lesions.¹⁹

Complete unloading and joint immobilization are known to have deleterious effects on cartilage healing due to reduced cartilage proteoglycan synthesis and thinning and softening of the cartilage.^4,22,50 This knowledge correlates with our observation that the minority of rehabilitation regimens for condylar (2/7)^1,3 and patellofemoral (2/8)^1,3 lesions adopted an initial period of nonweightbearing or full immobilization postoperatively. Instead, controlled range of motion and protected weightbearing regimens are adopted by most. This creates a pumping effect through repeated compressive and decompressive forces, sliding of articular surfaces, which aids the diffusion of solutes to promote cartilage hydration and nourishment for cartilage healing.^9,20

There was no clear difference in outcome between studies that designed rehabilitation regimens according to the lesion location and those that used a generic rehabilitation regimen regardless of the location. This is likely because there are multiple factors, such as lesion location and size, other than rehabilitation.

Among both the condylar and patellofemoral lesions, we observed that an earlier return to jogging and sports was conferred in the 3 groups that started with immediate weightbearing.^8,41,43 This did not correlate with poorer clinical or radiological outcomes. The mean duration of return to sports in the delayed weightbearing groups was 18 months, as compared with a mean of 5 to 6 months in the immediate weightbearing groups. The timeline to return to sports did not differ significantly between rehabilitation regimens for condylar and patellofemoral lesions, with both groups in the range of 4 to 18 months. This may suggest that immediate FWB accelerates the rehabilitation without compromising matrix integration and cartilage healing. Besides allowing earlier return to sports, this may also allow earlier return to work and improved quality of life and mitigate the negative effects of prolonged immobilization and atrophy from disuse postoperatively that one might face in delayed weightbearing protocols. Several randomized controlled trials in matrix-induced autologous chondrocyte implantation have similarly demonstrated that accelerated weightbearing protocols result in equivalent or superior functional outcomes without a compromise in graft integrity.^14-16 It needs to be borne in mind that patient selection and other factors contribute to the outcome. The current review included grade 3 or 4 lesions ranging from a mean size of 2.6 to 3.7 cm,² and there was no clear correlation between lesion size or grade and the outcome of the rehabilitation regimen. Hence, in appropriately selected patients, accelerating the weightbearing protocol may safely facilitate faster functional recovery without jeopardizing long-term clinical or structural outcomes.

Continuous passive motion is known to have significant evidence at a basic science level to reduce pain and promote knee ROM and cartilage healing.²⁵ However, clinical evidence on the use of continuous passive motion after articular cartilage surgery is lacking.¹⁷ We did not observe an association between the use of continuous passive motion and clinical outcomes, although there are reports of its positive effect on cartilage recovery.³⁰ Nevertheless, continuous passive motion remains a commonly used modality in the early phases of rehabilitation, as observed in the majority of the rehabilitation regimens outlined (8/14).

Although arthroscopy is considered the standard of reference for evaluating cartilage injury and repair, it is associated with the morbidity of anesthesia. MRI is a widely used noninvasive method for morphological assessment of the cartilage repair site.^32,55 In our review, MRI was the most commonly used outcome measure. The MOCART score provides a standardized set of radiographic parameters for quantification of cartilage repair, which has been proven to correlate with clinical outcomes.^34,36,44 While MRI is a sensitive diagnostic tool to detect moderate to severe cartilage lesions preoperatively, there is literature to suggest that the severity of cartilage injury on MRI does not have a strong correlation with clinical symptom severity.^21,39 Considering this modest relationship, postoperative MRI findings of cartilage regeneration should be interpreted in concert with functional outcome measures for a holistic assessment at follow-up after AMIC.

The main strength of this study lies in the systematic review and consolidation of rehabilitation regimens adopted in AMIC over the past 15 years, without concomitant procedures or pathologies that may influence rehabilitation. This has allowed for deeper analysis of rehabilitation regimens and better understanding of how they are influenced by location or characteristics of the lesion.

Limitations

There are several limitations to this study. Because of the heterogeneity in reporting of rehabilitation protocols and outcome measures and lack of patient-specific data, data analysis was largely descriptive, and our ability to perform a subgroup or meta-analysis was limited. Factors such as compliance with rehabilitation and access to formal physical therapy services may affect clinical outcomes, which are not known from the literature. There is a possible overlap in patient cohort between the studies by Schiavone Panni et al. (2011)⁴² and Schiavone Panni et al. (2018)⁴³; however, we were unable to confirm this with the corresponding authors. To avoid overstating the number of patients who commenced immediate weightbearing postoperatively for patellofemoral lesions, we excluded the former study based on this assumption. Nevertheless, this did not significantly change the qualitative trend in postoperative outcomes. Variations in the lesion size and location and surgical technique may also confound the analysis of rehabilitation regimens. Most studies exclude patients with multiple or bipolar lesions and significant malalignment, limiting the generalizability of our findings. Further prospective controlled studies are needed, with focus on direct comparison between rehabilitation regimens in a homogeneous cohort with uniform reporting of clinical outcomes.

In the current review, a correlation is observed between the initiation of ROM or weightbearing component of the rehabilitation protocol and the site of the lesion. ROM tends to be initiated earlier when the lesion is localized at the tibiofemoral joint, while weightbearing tends to be initiated earlier with a lesion located at the patellofemoral joint. The clinical outcome and postoperative MRI findings showed improvement in both protocols and suggest that a customized approach with ROM or weightbearing progression according to the lesion site plays an important role in the patient outcome.

Conclusion

Our review demonstrated that rehabilitation protocols varied according to the location of the lesion, with a general trend of earlier weightbearing for patellofemoral lesions, in comparison with earlier ROM for condylar lesions. In the current review, the postoperative clinical outcome and MRI findings are similar with both protocols, suggesting that this approach of customizing the ROM and weightbearing components in the rehabilitation protocol to the lesion site plays a role in the positive outcome.

Supplemental Material

sj-docx-1-ojs-10.1177_23259671251391794 – Supplemental material for Rehabilitation of the Knee After Autologous Matrix-Induced Chondrogenesis: A Systematic Review of Rehabilitation Protocols and Clinical and Radiological Outcomes

Supplemental material, sj-docx-1-ojs-10.1177_23259671251391794 for Rehabilitation of the Knee After Autologous Matrix-Induced Chondrogenesis: A Systematic Review of Rehabilitation Protocols and Clinical and Radiological Outcomes by Jonathan Yeo, Joseph Jon-yin Wan and Sir-Young James Loh in Orthopaedic Journal of Sports Medicine

Supplemental Material

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Supplemental material, sj-docx-2-ojs-10.1177_23259671251391794 for Rehabilitation of the Knee After Autologous Matrix-Induced Chondrogenesis: A Systematic Review of Rehabilitation Protocols and Clinical and Radiological Outcomes by Jonathan Yeo, Joseph Jon-yin Wan and Sir-Young James Loh in Orthopaedic Journal of Sports Medicine

Footnotes

Final revision submitted July 11, 2025; accepted September 8, 2025.

One or more of the authors has declared the following potential conflict of interest or source of funding: S.Y.J.L. has received honorarium from Smith & Nephew. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

ORCID iD

Jonathan Yeo

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References

Anders

Volz

Frick

Gellissen

A randomized, controlled trial comparing Autologous Matrix-Induced Chondrogenesis (AMIC^®) to microfracture: analysis of 1- and 2-Year follow-up data of 2 centers. Open Orthop J. 2013;7:133-143.

Arokoski

Jurvelin

Väätäinen

Helminen

HJ.

Normal and pathological adaptations of articular cartilage to joint loading. Scand J Med Sci Sports. 2000;10(4):186-198.

Bąkowski

Grzywacz

Prusińska

Ciemniewska-Gorzela

Gille

Piontek

Autologous matrix-induced chondrogenesis (AMIC) for focal chondral lesions of the knee: a 2-year follow-up of clinical, proprioceptive, and isokinetic evaluation. J Funct Biomater. 2022;13(4):277.

Behrens

Kraft

Oegema

Jr.

Biochemical changes in articular cartilage after joint immobilization by casting or external fixation. J Orthop Res. 1989;7(3):335-343.

Benthien

Behrens

Autologous matrix-induced chondrogenesis (AMIC). A one-step procedure for retropatellar articular resurfacing. Acta Orthop Belg. 2010;76(2):260-263.

Benthien

Behrens

Nanofractured autologous matrix induced chondrogenesis (NAMIC©)—further development of collagen membrane aided chondrogenesis combined with subchondral needling: a technical note. Knee. 2015;22(5):411-415.

Benthien

Behrens

Reviewing subchondral cartilage surgery: considerations for standardised and outcome predictable cartilage remodelling: a technical note. Int Orthop. 2013;37(11):2139-2145.

Bertho

Pauvert

Pouderoux

Robert

Treatment of large deep osteochondritis lesions of the knee by autologous matrix-induced chondrogenesis (AMIC): preliminary results in 13 patients. Orthop Traumatol Surg Res. 2018;104(5):695-700.

Buckwalter

JA.

Articular cartilage injuries. Clin Orthop Relat Res. 2002;(402):21-37.

10.

Buckwalter

Mankin

HJ.

Articular cartilage: tissue design and chondrocyte-matrix interactions. Instr Course Lect. 1998;47:477-486.

11.

Carballo

Nakagawa

Sekiya

Rodeo

SA.

Basic science of articular cartilage. Clin Sports Med. 2017;36(3):413-425.

12.

Curl

Krome

Gordon

Rushing

Smith

Poehling

GG.

Cartilage injuries: a review of 31,516 knee arthroscopies. Arthroscopy. 1997;13(4):456-460.

13.

Dorotka

Windberger

Macfelda

Bindreiter

Toma

Nehrer

Repair of articular cartilage defects treated by microfracture and a three-dimensional collagen matrix. Biomaterials. 2005;26(17):3617-3629.

14.

Ebert

Fallon

Ackland

Janes

Wood

DJ.

Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation. Am J Sports Med. 2020;48(1):133-142.

15.

Ebert

Fallon

Wood

Janes

GC.

An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery. Knee Surg Sports Traumatol Arthrosc. 2021;29(11):3825-3833.

16.

Edwards

Ackland

Ebert

JR.

Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: early clinical and radiological outcomes. Am J Sports Med. 2013;41(10):2314-2324.

17.

Fazalare

Griesser

Siston

Flanigan

DC.

The use of continuous passive motion following knee cartilage defect surgery: a systematic review. Orthopedics. 2010;33(12):878.

18.

Figueroa

Calvo

Vaisman

Carrasco

Moraga

Delgado

Knee chondral lesions: incidence and correlation between arthroscopic and magnetic resonance findings. Arthroscopy. 2007;23(3):312-315.

19.

Gowd

Weimer

Rider

, et al. Cartilage restoration for tibiofemoral bipolar lesions results in promising failure rates: a systematic review. Arthrosc Sports Med Rehabil. 2021;3(4):e1227-e1235.

20.

Graham

Moore

Burris

Price

Sliding enhances fluid and solute transport into buried articular cartilage contacts. Osteoarthritis Cartilage. 2017;25(12):2100-2107.

21.

Guermazi

Niu

Hayashi

, et al. Prevalence of abnormalities in knees detected by MRI in adults without knee osteoarthritis: population based observational study (Framingham Osteoarthritis Study). BMJ. 2012;345:e5339.

22.

Haapala

Arokoski

Pirttimäki

, et al. Incomplete restoration of immobilization induced softening of young beagle knee articular cartilage after 50-week remobilization. Int J Sports Med. 2000;21(1):76-81.

23.

Heir

Nerhus

Røtterud

, et al. Focal cartilage defects in the knee impair quality of life as much as severe osteoarthritis: a comparison of knee injury and osteoarthritis outcome score in 4 patient categories scheduled for knee surgery. Am J Sports Med. 2009;38(2):231-237.

24.

Hill

Vedi

Williams

Iwaki

Pinskerova

Freeman

MA.

Tibiofemoral movement 2: the loaded and unloaded living knee studied by MRI. J Bone Joint Surg Br. 2000;82(8):1196-1198.

25.

Howard

Mattacola

Romine

Lattermann

Continuous passive motion, early weight bearing, and active motion following knee articular cartilage repair: evidence for clinical practice. Cartilage. 2010;1(4):276-286.

26.

Hungerford

Barry

Biomechanics of the patellofemoral joint. Clin Orthop Relat Res. 1979;(144):9-15.

27.

Irrgang

Pezzullo

Rehabilitation following surgical procedures to address articular cartilage lesions in the knee. J Orthop Sports Phys Ther. 1998;28(4):232-240.

28.

Joshi Jubert

Vinaixa

Torres

, et al. AMIC achieves sustained clinical improvement in isolated patellar cartilage defects over 5 years, correlating with MRI. Knee Surg Sports Traumatol Arthrosc. 2025;33(6):2104-2113. doi:10.1002/ksa.12518

29.

Karpinski

Häner

Bierke

Petersen

Matrix-induced chondrogenesis is a valid and safe cartilage repair option for small- to medium-sized cartilage defects of the knee: a systematic review. Knee Surg Sports Traumatol Arthrosc. 2021;29(12):4213-4222.

30.

Knapik

Harris

Pangrazzi

, et al. The basic science of continuous passive motion in promoting knee health: a systematic review of studies in a rabbit model. Arthroscopy. 2013;29(10):1722-1731.

31.

Lee

Suzer

Thermann

Autologous matrix-induced chondrogenesis in the knee: a review. Cartilage. 2014;5(3):145-153.

32.

Liu

Tran

Skalski

, et al. MR imaging of cartilage repair surgery of the knee. Clin Imaging. 2019;58:129-139.

33.

Mankin

HJ.

The response of articular cartilage to mechanical injury. J Bone Joint Surg Am. 1982;64(3):460-466.

34.

Marlovits

Singer

Zeller

Mandl

Haller

Trattnig

Magnetic resonance observation of cartilage repair tissue (MOCART) for the evaluation of autologous chondrocyte transplantation: determination of interobserver variability and correlation to clinical outcome after 2 years. Eur J Radiol. 2006;57(1):16-23.

35.

Martelli

Pinskerova

The shapes of the tibial and femoral articular surfaces in relation to tibiofemoral movement. J Bone Joint Surg Br. 2002;84(4):607-613.

36.

McCarthy

McCall

Williams

, et al. Magnetic resonance imaging parameters at 1 year correlate with clinical outcomes up to 17 years after autologous chondrocyte implantation. Orthop J Sports Med. 2018;6(8):2325967118788280.

37.

Migliorini

Eschweiler

Maffulli

, et al. Autologous matrix-induced chondrogenesis (AMIC) and microfractures for focal chondral defects of the knee: a medium-term comparative study. Life (Basel). 2021;11(3):183.

38.

Migliorini

Maffulli

Baroncini

Bell

Hildebrand

Schenker

Autologous matrix-induced chondrogenesis is effective for focal chondral defects of the knee. Sci Rep. 2022;12(1):9328.

39.

Ota

Sasaki

, et al. Relationship between abnormalities detected by magnetic resonance imaging and knee symptoms in early knee osteoarthritis. Sci Rep. 2021;11(1):15179.

40.

Reinold

Wilk

Macrina

Dugas

Cain

EL.

Current concepts in the rehabilitation following articular cartilage repair procedures in the knee. J Orthop Sports Phys Ther. 2006;36(10):774-794.

41.

Schagemann

Behrens

Paech

, et al. Mid-term outcome of arthroscopic AMIC for the treatment of articular cartilage defects in the knee joint is equivalent to mini-open procedures. Arch Orthop Trauma Surg. 2018;138(6):819-825.

42.

Schiavone Panni

Cerciello

Vasso

. The manangement of knee cartilage defects with modified AMIC technique: preliminary results. Int J Immunopathol Pharmacol. 2011;24(1 suppl 2):149-152.

43.

Schiavone Panni

Del Regno

Mazzitelli

D’Apolito

Corona

Vasso

. Good clinical results with autologous matrix-induced chondrogenesis (AMIC) technique in large knee chondral defects. Knee Surg Sports Traumatol Arthrosc. 2018;26(4):1130-1136.

44.

Schreiner

Raudner

Marlovits

, et al. The MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) 2.0 Knee Score and Atlas. Cartilage. 2021;13(1 suppl):571s-587s.

45.

Sophia Fox

Bedi

Rodeo

SA.

The basic science of articular cartilage: structure, composition, and function. Sports Health. 2009;1(6):461-468.

46.

Stang

Critical evaluation of the Newcastle-Ottawa Scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603-605.

47.

Steadman

Rodkey

Rodrigo

JJ.

Microfracture: surgical technique and rehabilitation to treat chondral defects. Clin Orthop Relat Res. 2001;(391 suppl):S362-S369.

48.

Steinwachs

Guggi

Kreuz

PC.

Marrow stimulation techniques. Injury. 2008;39(1 suppl):26-31.

49.

Sterne

JAC

Savović

Page

, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.

50.

Vanwanseele

Lucchinetti

Stüssi

The effects of immobilization on the characteristics of articular cartilage: current concepts and future directions. Osteoarthritis Cartilage. 2002;10(5):408-419.

51.

Volz

Schaumburger

Frick

Grifka

Anders

A randomized controlled trial demonstrating sustained benefit of autologous matrix-induced chondrogenesis over microfracture at five years. Int Orthop. 2017;41(4):797-804.

52.

Waldman

Spiteri

Grynpas

Pilliar

Hong

Kandel

RA.

Effect of biomechanical conditioning on cartilaginous tissue formation in vitro. J Bone Joint Surg Am. 2003;85-A(suppl 2):101-105.

53.

Wallace

Salem

Salinas

Powers

CM.

Patellofemoral joint kinetics while squatting with and without an external load. J Orthop Sports Phys Ther. 2002;32(4):141-148.

54.

Wiewiorski

Miska

Kretzschmar

Studler

Bieri

Valderrabano

Delayed gadolinium-enhanced MRI of cartilage of the ankle joint: results after autologous matrix-induced chondrogenesis (AMIC)-aided reconstruction of osteochondral lesions of the talus. Clin Radiol. 2013;68(10):1031-1038.

55.

Yang

Brusalis

Fabricant

Greditzer

HG.

Articular cartilage repair in the knee: postoperative imaging. J Knee Surg. 2021;34(1):2-10.

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