Surface-based treatment options for cartilage lesions of the knee

Introduction

Lesions of articular cartilage of the knee are a common problem that can affect a wide variety of patients, from young athletes to older adults. The hyaline articular cartilage plays a key role in distributing loads and providing a smooth surface during joint movement. However, due to the avascular and aneural nature of articular cartilage, it offers limited intrinsic healing potential, making cartilage lesions a challenging problem for both physicians and patients. Even small lesions rarely heal spontaneously and often progress to pain, swelling, mechanical dysfunction, and early osteoarthritis (1). Full-thickness defects in high-load-bearing zones, such as the femoral condyles or patellofemoral joint, are primarily symptomatic because altered biomechanics accelerate degeneration and disproportionately impair function (2).

The management of articular cartilage lesions can be broadly categorized into two main types. The first is surface-based treatments, and the second is osteochondral restorative procedures. The surface-based chondral therapies are best suited for contained lesions without subchondral bone involvement. Various types of treatments fall within this category, including marrow stimulation techniques, scaffold-augmented approaches [e.g., autologous matrix-induced chondrogenesis (AMIC)], matrix-induced autologous chondrocyte implantation (MACI), and particulated cartilage techniques using autograft or allograft tissue. The second category comprises therapy modalities that utilize restorative techniques to address defects involving both the articular cartilage and the underlying subchondral bone. Osteochondral restorative procedures are indicated for combined chondral-subchondral pathology and include osteochondral autograft transfer for smaller defects, fresh osteochondral allograft transplantation for larger bone-involving lesions, and biphasic scaffolds such as Agili-C, which have reported size limitations of approximately 7 cm² or autologous chondrocyte implantation (ACI) with concomitant bone augmentation (3). These procedures restore both the articular cartilage surface and the underlying subchondral bone, which is critical because cartilage restoration techniques performed in the setting of compromised subchondral bone are prone to failure due to inadequate mechanical support and biologic integration.

Treatment selection is guided by patient age and activity level, as well as lesion-specific factors including size, depth, location, containment, alignment, and the status of the subchondral bone. Age and activity level are key components in several treatment algorithms, as younger and more active patients have demonstrated more favorable short-term outcomes following microfracture and scaffold-based cartilage repair (e.g., AMIC) compared with older patients (4,5). In this context, a more durable approach refers to cell-based cartilage restoration or osteochondral procedures that address both the chondral surface and, when necessary, the subchondral bone, thereby providing more predictable long-term structural integrity and clinical outcomes than marrow stimulation techniques alone. The depth and size of the lesion are other crucial prognostic factors to consider when deciding on treatment plans, as these two variables help stratify the type of interventions a patient receives. A small, contained surface lesion that is deemed to be <2 cm² can be treated with microfracture or AMIC. Larger full-thickness lesions, which typically range from 2 to over 4 cm², may require osteochondral allograft transplantation or a cell-based approach such as ACI. Another essential variable to be considered is the location of the lesion. The location of the lesion can play a critical role in influencing procedure outcomes, as particular locations, such as patellofemoral defects, require a more robust repair compared to other places in the knee (6,7). Importantly, when subchondral bone integrity is compromised, surface-based cartilage restoration procedures are less reliable, as failure to restore the osseous foundation can lead to graft collapse, incomplete integration, and inferior clinical outcomes. Subchondral bone density is another critical determinant of treatment selection. When subchondral bone integrity is compromised, it is recommended to proceed with a restorative osteochondral procedure as it provides superior outcomes (8,9).

Over the past several decades, significant advances have been made in surface-based cartilage repair. Microfracture remains a widely used procedure, popularized due to its ability to offer a less invasive, less expensive, yet highly effective way of treating cartilage lesions (4). However, its use is limited by defect size and the poor long-term durability of fibrocartilage repair. To address this, augmentation strategies using scaffolds, growth factors, and hydrogels have been developed to improve tissue quality and longevity (4). AMIC was introduced in the early 2000 s, combining microfracture with a collagen scaffold to enhance repair morphology (10). In recent years, a new technique has emerged as an innovative approach to treating chondral lesions. The particulated cartilage technique has emerged as a single-stage biologic solution promoting hyaline-like repair. The particulated cartilage technique includes micronized extracellular matrix (BioCartilage), particulated juvenile allograft cartilage (PJAC, DeNovo NT), or adult (CartiMax) allograft cartilage, and particulated autologous cartilage implantation. MACI techniques continue to expand, with MACI, CartiMax, NeoCart, and BioSeed-C representing innovative constructs designed to optimize durability and long-term outcomes (11). The development of these new techniques will provide a much-needed update to these various treatment algorithms, helping patients receive a more comprehensive and suitable plan based on multiple patient and lesion factors. These developments mark a shift from simple marrow stimulation towards biologically enhanced surface restoration. This review will examine the current landscape of surface-based treatment options for cartilage lesions of the knee, highlighting their biological rationale, clinical outcomes, and evolving role in joint preservation. Special consideration is given to patellofemoral cartilage lesions, which present unique biomechanical and clinical challenges and often require treatment strategies distinct from those used in the tibiofemoral compartment.

Micronized cartilage extracellular matrix aka BioCartilage

Micronized cartilage extracellular matrix (MCEM aka BioCartilage, Arthrex, Naples, FL, USA) is an acellular scaffold composed of extracellular matrix contents that are native to articular cartilage, including type II collagen, proteoglycans, and various chondrogenic growth factors (12). The product is manufactured from hyaline cartilage from tissue donors, which is formed into dehydrated particles in the micron size range, allowing for increased surface area to be covered by the scaffold (13). The surgical technique can be performed all-arthroscopically and begins by first preparing the chondral defect to remove/debride any remaining cartilage. The site is then additionally prepared with microfracture. The MCEM powder is mixed with autologous blood and injected into the cartilage defect site, providing a scaffold over which progenitor cells [namely mesenchymal stem cells (MSCs)] can migrate through the microfracture holes, attach, and differentiate (14). Figure 1A-1C demonstrate a case of a 39-year-old female with a full-thickness trochlear 12 mm × 12 mm Grade IV chondral defect with delamination, treated with debridement, microfracture and BioCartilage implantation sealed with fibrin glue.

Figure 1 MRI (A), arthroscopic (B) and intraoperative (C) images from a 39-year-old female with a full-thickness trochlear chondral defect with delamination. After debridement, the lesion measured 12 mm × 12 mm (Grade IV) and was treated with microfracture followed by BioCartilage implantation sealed with fibrin glue. MRI, magnetic resonance imaging.

An early animal model study published in 2016 compared microfracture with MCEM to microfracture alone in equine trochlear defects. The authors demonstrated significantly improved International Cartilage Repair Society (ICRS) repair scores for MCEM + microfracture compared to microfracture alone, as well as significantly better histologic scores for repair-host integration (15).

A 2021 research article prospectively studied 48 patients (mean age, 31.6±10.5 years) who underwent cartilage allograft extracellular matrix procedures on the knee over a 2-year period (16). The patients were operated on at eight sites by eight separate surgeons. The average defect depth was 3.6±3.4 mm, and the average defect area was 2.4±1.4 cm². About half of the lesions were in the trochlea (51.1%), followed by the lateral femoral condyle (22.4%), the patella (12.2%), the medial femoral condyle (10.2%), and the lateral tibial plateau (4.1%). Outcomes included standard knee outcome assessments at 3, 6, 12, and 24 months. The authors found a statistically significant improvement in the visual analogue scale (VAS), International Knee Documentation Committee (IKDC), and several subsets of the Knee Injury and Osteoarthritis Outcome Score (KOOS) score. The 12-item short form health survey (SF-12) physical activity scores also significantly improved. The Marx Activity Rating scale, however, was found to be significantly worse.

Treatment failure occurred in one patient (2.1%) in the form of graft delamination, which was diagnosed during a second-look arthroscopy. This was diagnosed 9.5 months after the initial operation and was treated with debridement alone; no further operation was required during the follow-up period. One patient (2.1%) also had a complication of persistent clicking, grinding, and crepitus 15 months after the initial surgery. This did not require any additional operations.

Ten patients underwent a 2-year follow-up MRI. The mean total magnetic resonance observation of cartilage repair tissue (MOCART) 2.0 score (measured on a scale from 0–100, a higher score indicating better quality cartilage) was only 40.5, with a standard deviation of 22.9 and a range from 15 to 70. Overall, the authors reported that clinically significant outcomes were achieved in 85–90% of the patients studied.

A smaller prospective study, published in 2020, reported on the clinical outcomes of 10 patients (mean age, 39.7; range, 19–66 years) who underwent microfracture augmented with MCEM and platelet-rich plasma (PRP) for isolated, contained chondral defects of the knee (17). Half of the defects were on the trochlea, and the other half were located on the femoral condyle. Outcomes measures included standard post-operative knee clinical outcome scores, as well as a post-operative MRI obtained at 1 year to measure the quality of the repaired cartilage and the percentage of defect fill. At each time point (6 months, 1 year, and 2 years), patients reported significantly improved IKDC, KOOS-JR, and SF-12 Physical Health scores. Nine out of the ten patients were able to return to their pre-injury level of work by one year post-operatively. Half of the patients were able to return to their pre-injury level of sport within 2 years. This study reported no intraoperative or postoperative complications, and no additional procedures were required related to the chondral defect during the 2-year follow-up period.

Interestingly, the 1-year post-operative MRIs demonstrated complete integration of the MCEM into the border zone in only 20% (n=2) of the cases. The remaining patients were found to have repair tissue that was less than 50% integrated. One patient showed an intact repair surface. Half (n=5) of the cases showed that more than half of the repaired surface was covered with ulcerations or showed complete degeneration. All of the cases exhibited disrupted subchondral bone, while 80% (n=8) of the repair sites remained hyperintense compared to the adjacent cartilage. Additionally, a majority of patients (70% or n=7) had a residual mild or moderate joint effusion at 2 years.

In a preclinical equine model, Fortier et al. [2016] compared microfracture alone versus microfracture plus MCEM. They found that MCEM-treated defects showed significantly better ICRS repair scores, more organized collagen II expression, and enhanced integration with surrounding cartilage (15). These histologic findings suggested that the mechanism of extracellular matrix scaffold is more likely hyaline-like cartilage formation rather than fibrocartilage repair.

In a larger multicenter registry from 2021, Cole et al. evaluated 48 patients treated with microfracture plus micronized cartilage extracellular matrix across multiple institutions. This study demonstrated statistically significant improvements in VAS, KOOS, and IKDC scores at a mean of 17.2 months postoperatively (16). The overall reoperation rate was 2.1%, with only one patient requiring a second arthroscopy for cartilage debridement. These findings suggest that MCEM may improve both the quality of the new cartilage tissue and the percentage of defect fill, especially when used in combination with biologic adjuncts (e.g., PRP or BMAC).

Imaging studies have also been published to investigate the maturation process of the repair tissue. Although early postoperative MRI findings often demonstrate partial defect fill and signal heterogeneity, these findings may reflect ongoing remodeling rather than failed integration.

Overall, while short- to mid-term clinical outcomes (≤2 years) with MCEM are promising, longer-term (>2 years) data is still limited. Current evidence supports MCEM as a safe and effective augmentation strategy for small to moderate contained chondral defects, capable of improving both clinical outcomes and repair tissue quality, especially when compared with microfracture alone. Ongoing prospective trials and registry studies will be paramount in determining the long-term durability, optimal biologic adjuncts, and comparative effectiveness of this technique relative to the other surface restoration methods discussed in this review.

PJAC aka DeNovo

PJAC (aka DeNovo NT Natural Tissue Graft, Zimmer Inc., Warsaw, Indiana, USA) is an allograft product that consists of articular cartilage from donors between the ages of 0 and 13 years old. The cartilage is harvested from donor femoral condyles and cut into cubes approximately 1 mm³ (18). After an open approach via arthrotomy and preparation/debridement of the chondral defect site, PJAC is typically applied in a single monolayer and secured in place with a layer of fibrin glue. Chondrocytes are thought to migrate from the juvenile particulate cartilage and form a new hyaline-like cartilage tissue matrix, which then integrates with the adjacent cartilage. Figure 2A-2C demonstrate PJAC implantation for a femoral condyle lesion following failed microfracture.

Figure 2 Intraoperative images demonstrating PJAC implantation for a femoral condyle lesion following failed microfracture. (A) Chondral lesion prior to debridement; (B) lesion after debridement; (C) lesion after PJAC implantation. PJAC, particulated juvenile allograft cartilage.

PJAC has several benefits: it requires only a single procedure, eliminating the need to ream into the subchondral bone, as in an osteochondral allograft, or harvest autologous tissue. Additionally, it leaves the door open for future osteochondral procedures if needed later. It has also been suggested to be more cost-effective than MACI in a Markov model, given its single-stage nature and lower graft cost (19).

One of the earliest studies reporting on outcomes of PJAC in the knee was published in 2011 and reported on the first four patients of a multicenter, prospective, single-arm, 25-subject case study (20). Standard PROs (KOOS, IKDC, VAS) were collected, and all three outcomes were shown to be improved at 24 months.

A 2014 study from the same cohort further performed MRIs at baseline, and 3, 6, 12, and 24 months post-operatively (21). Patients were also given the choice to voluntarily undergo diagnostic arthroscopy and cartilage biopsy to assess the repair site histologically, which was performed in eight knees. This included safranin O staining for proteoglycans and immunostaining for type I and II collagen. PROs were again significantly improved from the pre-operative baseline. The postoperative MRIs suggested that the PJAC grafts linearly reorganized and matured over time, nearing a level similar to that of native cartilage at the 2-year mark, as inferred from T2 relaxation times and weighted scores. MRIs also showed linearly increasing defect fill (43.5%±48.5% at 3 months to 109.7%±62.9% at 2 years). Eight knees were able to undergo histologic analysis of full-thickness articular cartilage, the chondro-osseous junction, and at least 5 mm of subchondral bone. The biopsies showed a mix of hyaline and fibrocartilage, with 3 out of the 8 samples displaying mainly hyaline cartilage, and most of the samples (6/8) had more type II collagen than type I. Both histology and diagnostic arthroscopy suggested good integration of the grafts with native tissue. Adverse events were essentially similar to those of other cartilage repair procedures. Notably, one partial delamination and one complete delamination were noted during the elective post-operative diagnostic arthroscopies/biopsies. The partial delamination was about 10% and was treated with debridement and microfracture, while the patient with complete delamination was notably completely asymptomatic, and loose body removal was performed. Except for the patient who underwent debridement and microfracture and the patient who underwent loose body removal, no additional procedures were required during the follow-up period. Another study analyzed 29 male Army service members with 36 treated chondral defects, a mean age of 33 years, for a mean follow-up of 16.2 months (22). In this cohort, 14 patients (48%) were medically discharged due to knee-related issues, with one patient being converted to a total knee replacement, and more than half of the patients reporting persistent knee pain at their latest follow-up.

Recent studies have focused on the application of PJAC to patellofemoral cartilage defects. A 2024 article retrospectively reviewed 41 knees that received PJAC to the patellofemoral joint and reported on PROs, return to sport, and complication/re-operation rates (23). The mean age was 23.4 years, and the mean follow-up period was 30.3 months. Post-operative PRO scores demonstrated lower levels of residual knee pain and good return to daily function. Notably, only 44% of patients completed the post-operative PRO questionnaires. Of the 17 patients who were playing sports at a high school or collegiate level pre-operatively, 100% (17/17) were able to return to their sport. The average time to return to sport was 8.2±2.7 months. In terms of post-operative complications, 29.3% (12/41) developed some type of complication, the most common being residual anterior knee pain. 8 revision surgical procedures were required in 6 of the 41 knees (14.6%).

Another retrospective study published in 2022 reported postoperative outcomes specifically in patients under the age of 21 years (24). They included 36 knees in 34 patients, all of whom had a minimum follow-up of 1 year and underwent a postoperative MRI at 6 months or later. The mean age in this study was 16.1 years. Of the 25 patients who participated in organized sports prior to surgery, all 25 (100%) were able to return to the same or higher level of sport than before their injury. Post-operative MRIs were graded via the ICRS’ standardized scoring system. An overall score of Grade II (8-11) was assigned to 64% of patients (23/36), with one patient receiving a perfect score of 12, indicating the repaired cartilage as Grade I or normal. With regard to filling of the chondral defect, 78% of patients (28/36) had graft filling of 50% or greater, 56% (20/36) had 75% or greater defect fill, and 31% (11/36) had PJAC found to be level with the native cartilage, filling 100% of the prior chondral lesion.

While the idea of assessing cartilage defect fill on postoperative MRI is appealing, it remains unclear whether this is clinically significant. A 2024 retrospective review sought to address the question, investigating whether PRO scores were correlated with defect fill on MRI 70 knees in 65 patients were reviewed, while nearly all post-operative PRO scores were significantly improved post-operatively and the majority of patients demonstrated more than two-thirds cartilage defect fill. No significant association was found between PRO scores and cartilage defect fill. Interestingly, there were no significant differences between cartilage defect fill percentages at 3-month, 6-month, 1-year, and 2-year follow-ups (25). In addition to clinical and imaging outcomes, basic science studies have demonstrated that juvenile chondrocytes used in PJAC exhibit favorable gene expression profiles, including upregulation of chondrogenic and extracellular matrix-related genes, supporting their biologic growth and regenerative potential (26).

PJAC provides some unique advantages, mainly due to the use of viable juvenile chondrocytes, which possess high metabolic activity and a robust capacity for extracellular matrix synthesis (27). These properties contribute to the formation of higher-quality repair tissue compared to traditional adult allografts (21). Additionally, PJAC has demonstrated the potential for use on load-bearing articular surfaces in short-term studies; however, the durability of this technique remains incompletely defined, particularly given the relatively short follow-up periods and the notable rates of persistent knee pain and postoperative complications reported in some cohorts (28).

MACI

MACI (Vericel, Cambridge, MA, USA) is a third-generation evolution of the ACI technique. The first generation of ACI required harvesting autologous chondrocytes, expanding them in vitro, and implanting them under a periosteal flap. The second generation replaced the periosteal cover with collagen membranes. The third generation, MACI, differs by using a porcine collagen membrane scaffold to seed the autologous chondrocytes, which is then cut to size intraoperatively and fixed into the defect site using fibrin glue. This technique reduces operative time, decreases the risk of periosteal hypertrophy, and allows for a more uniform cellular distribution within the scaffold (15,27).

The surgical technique is performed in two stages. The first stage involves an arthroscopic procedure to biopsy healthy cartilage from a non-weight-bearing region of the knee, such as the inner margin of the intercondylar notch. A full diagnostic arthroscopy is performed at this time, as well as a simple chondroplasty. The biopsied cells are expanded in vitro over several weeks before being embedded into a collagen membrane scaffold. During the second stage, an arthrotomy is typically made, and the defect is prepared by removing unstable cartilage and creating stable vertical margins. The MACI membrane is then sized and shaped to the defect and secured with fibrin glue. Post-operative rehabilitation typically emphasizes early controlled motion with delayed return to impact activities to optimize integration and cartilage maturation (21). Figure 3 demonstrates a case of a 39-year-old female with full-thickness chondral loss of the central patella and trochlea, who underwent stage MACI biopsy, followed by implantation of one MACI graft to the patella and two grafts to the trochlea.

Figure 3 Case of a 39-year-old female with full-thickness chondral loss of the central patella and trochlea. (A) Intraoperative view following debridement and chondroplasty of both lesions during stage 1 arthroscopy with MACI biopsy. (B) Prepared MACI grafts prior to implantation. (C) Final implantation of one MACI graft to the patella and two grafts to the trochlea in a “snowman” configuration, performed in conjunction with tibial tubercle anteromedialization at the time of MACI implantation, which occurred 4.5 months after the index biopsy procedure. MACI, matrix-induced autologous chondrocyte implantation.

Clinical outcomes following MACI implantation have been extensively studied in both randomized controlled trials and long-term cohort studies. The 2014 SUMMIT trial was a multicenter, randomized controlled trial comparing MACI to microfracture for symptomatic cartilage defects ≥3 cm². At 2 years, MACI demonstrated significantly better KOOS pain and function scores, with these improvements lasting through 5-year follow-up (29). Brittberg et al. demonstrated sustained clinical improvement following MACI at mid-term follow-up, with significantly superior PROs compared with microfracture at 5 years in a randomized controlled trial (30). Importantly, longer-term cohort studies have since shown that these clinical gains are durable beyond 10 years, with the majority of patients maintaining good to excellent functional outcomes, high satisfaction, and low rates of graft failure, despite the absence of randomized long-term comparators (31). Systematic reviews and meta-analyses of cartilage repair techniques have similarly reported that ACI procedures, including MACI, are associated with superior PROs on select measures compared with marrow stimulation techniques, and may provide particular benefit in younger, active patients with larger cartilage defects (32,33).

Imaging and histologic studies provide further support for the biological efficacy of MACI. MRI-based evaluations, including MOCART and T2 mapping, have demonstrated progressive defect filling with tissue quality resembling that of hyaline cartilage rather than fibrocartilage. MRI studies have demonstrated biochemical improvements in the new tissue, supporting the premise that MACI promotes durable cartilage regeneration (34).

More recent studies have expanded upon these findings, providing long-term data extending beyond 10 years. Wang et al. published a systematic review in 2024 of patients treated with MACI and reported durable improvements in PROs at 10–17 years, with all-cause reoperation rates of ~9% and conversion to total knee arthroplasty in 7.4% of cases (35). A 2024 study by Ebert and colleagues reported ≥10-year outcomes in a large prospective cohort, finding significant and sustained improvements in PROs, with 92% of patients satisfied with pain relief and 76% satisfied with return to sport. Importantly, graft failure rates were relatively low (~9–11%), and outcomes were somewhat more favorable in tibiofemoral compared to patellofemoral lesions (31). A companion study focused on patellofemoral MACI showed high rates of patient satisfaction (~90%) and durable improvements at a mean of 11.9 years follow-up, with no significant differences in outcomes between grafts to the patella vs. trochlea (36).

Prognostic factors have also been described in recent literature. A 2023 paper by Liu et al. reported that defect sizes ≥4 cm² and higher body mass index (BMI) were associated with worse KOOS scores, as well as poorer MRI MOCART scores, at a mean follow-up of 5.5 years (37). These findings highlight the importance of patient selection and counseling when considering MACI.

Overall, MACI has become a widely accepted surface cartilage restoration option for large, symptomatic, isolated defects of the knee, in patients without advanced osteoarthritis. In contrast to particulated cartilage techniques, MACI has demonstrated significant and durable clinical improvements extending beyond 10 years, as evidenced by randomized controlled trials and long-term cohort studies (31,35,36,38). Its main limitations remain the requirement for a two-stage procedure and higher upfront costs, although cost-effectiveness analyses suggest that long-term durability may offset these concerns when compared with marrow stimulation techniques.

Particulated cartilage allograft (CartiMax)

CartiMax (CONMED, Largo, FL, USA) is a particulated articular cartilage allograft derived from adult human donors. Unlike PJAC, which is harvested from donors between the ages of 0–13 years, CartiMax is obtained from mature adult cartilage. The graft is processed into small particulates and stored cryopreserved, preserving viable chondrocytes as well as extracellular matrix proteins such as type II collagen and proteoglycans. Once thawed intraoperatively and mixed with a cartilage activation mixture (CAM), the particulated graft can be packed into a prepared chondral defect and secured with fibrin glue. The rationale behind CartiMax is that chondrocytes from the allograft fragments migrate outward, proliferate, and produce new hyaline-like cartilage matrix that integrates with the surrounding host cartilage (20,39).

The surgical technique involves arthroscopic or mini-open preparation of the chondral defect, with removal of unstable cartilage and creation of stable vertical margins. Subchondral bone is preserved, distinguishing CartiMax implantation from osteochondral allograft transplantation. The defect is dried thoroughly, after which the thawed particulated allograft is delivered into the defect and tamped to fill the space. Fibrin glue is applied to secure the fragments in place and provide stability during the early postoperative period. Rehabilitation protocols for cartilage restoration procedures are similar to those for other procedures, involving early protected weight-bearing and a gradual return to activity over several months (40).

Clinical evidence for CartiMax is more limited compared to MACI or PJAC, as the product has only been available since 2017. Early animal studies demonstrated that particulated adult cartilage allografts can survive, remodel, and integrate within chondral defects. A 2024 study discussed an earlier goat model that showed viable chondrocytes within implanted cartilage fragments and extracellular matrix production bridging graft and host tissue (41).

Early human clinical data for CartiMax/viable cartilage allograft remain limited. In a prospective case series later published by Desai et al., 20 patients with focal knee cartilage defects, primarily patellar and femoral condyle lesions, were treated with viable cartilage allograft. At a mean clinical follow-up of 24.1 months, IKDC, Lysholm, KOOS subscales, and pain-related outcomes improved from baseline. MRI follow-up demonstrated solid defect fill and integration with limited bone signal, and early second-look arthroscopy showed graft incorporation without delamination. However, the study was small, uncontrolled, and did not include 48 patients or report two graft delaminations.

Overall, CartiMax offers the advantages of a single-stage procedure, off-the-shelf availability with a long shelf life, without donor site morbidity, and relative ease of implantation compared to two-stage techniques such as MACI. Limitations include the lack of long-term outcome data, variable integration observed on imaging, and potentially lower chondrocyte viability compared to juvenile allograft cartilage. As larger prospective studies mature, CartiMax will be better defined within the cartilage repair algorithm, particularly for patients seeking a single-stage solution for moderate-sized chondral defects.

NeoCart

NeoCart (Histogenics, Waltham, MA, USA) is a tissue-engineered cartilage implant designed to treat focal chondral lesions. NeoCart is a tissue-engineered cartilage implant prepared through a multi-step process in which chondrocytes are harvested autologously and then expanded ex vivo. It is then seeded into a 3D type 1 collagen honeycomb scaffold and matured under controlled bioreactor conditions before undergoing second-stage implantation into a debrided focal defect, followed by fixation with a collagen- and fibrin-based bioadhesive (42,43). For a patient to receive a NeoCart, several indications must be met before the procedure takes place. The patient has been exhibiting symptoms and has a contained ICRS grade of three to four focal chondral lesions of the femoral condyle with preserved alignment, ligamentous stability, and meniscal function (43,44). Lesion size was typically around 1–3 cm² (mean lesion sizes ≈2.5–2.9 cm² in trials), and without advanced tibiofemoral osteoarthritis (43,44). These indications mirrored those used in Food and Drug Administration (FDA)-regulated trials. Several early safety studies were conducted on NeoCart. Notably, Crawford et al. [2009] demonstrated favorable outcomes in 8 patients. The prospective study showed that patients who had received the NeoCart reported significant reductions in pain at 12 and 24 months. MRI evidence of integration with 67–100% defect fill by 24 months, and no arthrofibrosis or graft hypertrophy, establishing the safety profile of the implant (42). There was another pivotal multi-center, randomized controlled trial that looked to compare NeoCart with the microfracture, which is considered the primary standard of care for osteochondral lesions. They used a 2:1 allocation (NeoCart, n=21; microfracture, n=9). The study found that NeoCart demonstrated significantly greater clinical efficacy at 6, 12, and 24 months (44). Improvements favored NeoCart for KOOS pain at all timepoints (P<0.05), IKDC and KOOS Sports at 12 and 24 months, and KOOS QOL at 24 months. VAS pain scores were significantly better at 12 and 24 months, and the proportion of “therapeutic responders” was higher in the NeoCart group at 6 months (43% vs. 25%), 12 months (76% vs. 22%), and 24 months (79% vs. 44%). A 5-year follow-up of 29 patients revealed significant improvements in IKDC and KOOS scores. The MRI of the patients showed progressive tissue maturation by 24 months and stability through 60 months, despite subchondral bone changes (45).

BioSeed-C

BioSeed-C (BioTissue Technologies, Freiburg, Germany) is a matrix-based ACI technique used to treat focal chondral lesions of the knee. This technique uses expanded chondrocytes that are suspended in fibrin and embedded in a resorbable gel-polymer scaffold, which is then subsequently implanted into a debrided defect and secured with sutures. Similar to other techniques, the use of BioSeed-C requires that the patient be symptomatic and have a contained ICRS grade of three to four on the femoral condyle, trochlea, or patella (46). The lesions in which BioSeed-C is typically used are 1–4 cm², with intact alignment, stability, and meniscal function (46). A prospective study looked to evaluate the short- to mid-term efficacy of BioSeed-C for the arthrotomic and arthroscopic treatment of posttraumatic and/or degenerative cartilage lesions of the knee (47). The study included 40 participants with a 2-year follow-up before the implantation and 3, 6, 12, and 24 months after implantation using the modified Cincinnati Knee Rating System, Lysholm score, and the KOOS, as well as histological analysis of second-look biopsies (47). The study found that patients who had the BioSeed-C procedure had significant improvement (P>0.05) in the Cincinnati, Lysholm, KOOS, and SF-26 scores, with second-look biopsies showing hyaline-like areas and good integration (45). The result of this study suggested that BioSeed-C can generate high-quality repair tissue compared to fibrocartilage alone, which is a significant limitation of microfracture (47). Another study examined 19 patients with early degenerative changes over the course of a four-year follow-up. The 19 patients who underwent the BioSeed-C procedure experienced gains in Lysholm, IKDC, and KOOS scores. MRIs in 16 out of the 19 patients indicated in this study showed moderate to complete filling. To examine the durability of BioSeed-C, a study was conducted on 52 patients with an ICRS grade of three to four. Patients were clinically scored preoperatively and at 48 months using the Lysholm, IKDC, ICRS KOOS, and Noyes scores. The research showed a significant Lysholm (from 51.8 preoperatively to 80.7 at 48 months postoperatively), IKDC (from 47.5 to 71.5), ICRS (from 3.8 to 2.0), KOOS (subcategory pain from 62 to 78, symptoms from 68 to 76, activities of daily living from 68 to 85, sports from 19 to 55, and quality of life from 30 to 55), and Noyes (from 31 to 59) scores (P≤0.001) 48 months after implantation of BioSeed-C compared with the preoperative situation with MRI showing moderate-to-complete defect fill in 43/44 evaluable knees (48). There are various complications associated with ACI platforms, including hypertrophy, distributed fusion, delamination, and rare graft failures, but matrix-based techniques such as BioSeed-C report fewer hypertrophy events compared with first-generation periosteum-covered ACI (46). The result of these several studies indicates that the BioSeed-C is a reliable option for medium-sized contained chondral defects, due to safety standards and high durability.

Emerging single-stage techniques have also been described, including autologous cartilage particulation methods (AutoCart), which involve harvesting cartilage shavings arthroscopically using a capture device and combining them with biologic scaffolds such as micronized cartilage extracellular matrix. Early European studies suggest promising short-term outcomes; however, clinical data remain limited, and further prospective evaluation is needed before widespread adoption.

Conclusions

Surface cartilage therapies for the knee have evolved from marrow-stimulated fibrocartilage repair toward biologically enhanced strategies that can be broadly categorized into two general approaches: single-stage particulated cartilage techniques and two-stage matrix-associated ACI. Across all cartilage restoration techniques, appropriate patient selection remains critical, as untreated malalignment, ligamentous instability, or meniscal deficiency can compromise graft integration and lead to failure regardless of the specific biologic or scaffold-based strategy employed. Accordingly, lesion characteristics—including size, containment, anatomic location (particularly within the patellofemoral joint), and subchondral bone integrity—should anchor any treatment algorithm.

Particulated cartilage techniques, including particulated juvenile cartilage, micronized cartilage extracellular matrix augmentation, and adult particulated cartilage allografts, offer single-stage, off-the-shelf solutions that reduce procedural burden and avoid cell expansion. Early clinical outcomes are generally encouraging for small to moderate contained defects; however, the available evidence is primarily limited to short-term follow-up, with mixed MRI findings and variable performance in patellofemoral lesions. As such, these techniques represent attractive options for carefully selected patients but require further long-term evaluation to define durability and optimal indications better.

In contrast, matrix-associated ACI—most notably MACI—is supported by a robust body of evidence, including randomized comparisons with microfracture and long-term follow-up extending beyond 10 years. These studies consistently demonstrate durable clinical improvements, acceptable reoperation rates, and more predictable outcomes, particularly for larger symptomatic isolated lesions in well-aligned, stable knees without advanced osteoarthritis. Other cell-based constructs, such as NeoCart and BioSeed-C, have also demonstrated meaningful short- to mid-term clinical gains and favorable histologic and MRI profiles, supporting their role in appropriately selected medium-sized defects.

Complication profiles across surface cartilage restoration techniques are generally acceptable, although failure mechanisms differ between approaches, including delamination, graft hypertrophy, and incomplete integration. These differences underscore the importance of meticulous defect preparation, secure graft fixation, and structured postoperative rehabilitation. Cost and logistical considerations—such as two-stage surgery, cell expansion, and implant pricing—remain practical constraints; however, the long-term durability demonstrated by higher-end options such as MACI may offset these factors in selected patients.

For small, contained defects with intact subchondral bone, scaffold-augmented microfracture or particulated cartilage approaches are reasonable. For larger (≥2–3 cm²), symptomatic isolated lesions in well-aligned, stable knees, matrix-associated ACI offers the most consistently durable outcomes to date. When subchondral bone integrity is compromised, treatment should shift toward osteochondral restorative procedures. Ultimately, a lesion- and patient-specific strategy—combined with sound surgical technique and rehabilitation—remains the cornerstone of successful joint preservation.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editor (Brian Waterman) for the series “The Medial Knee at Risk” published in Annals of Joint. The article has undergone external peer review.

Peer Review File: Available at https://aoj.amegroups.com/article/view/10.21037/aoj-2025-1-86/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aoj.amegroups.com/article/view/10.21037/aoj-2025-1-86/coif). The series “The Medial Knee at Risk” was commissioned by the editorial office without any funding or sponsorship. E.J.S. reports the following relationships: paid consultant for Arthrex Inc., Flexion Therapeutics, Globus Medical, Joint Restoration Foundation, Organogenesis Inc., Smith & Nephew, Subchondral Solutions, and Vericel; speaker’s bureau/presenter for Arthrex Inc. and Vericel; research support from Cartiheal and Organogenesis Inc.; and stock options in Better PT and Overture Orthopaedics. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are 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. Written informed consent was obtained from each patient for the publication of this article and accompanying clinical images.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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