Articular cartilage is composed of hyaline cartilage and allows for low-friction movement of the joint. Traumatic mechanical destruction or progressive wear and tear can destroy the cartilage and cause symptoms such as pain, swelling, and decreased range of motion.

Athletes are known to be at higher risk for traumatic cartilage injuries due to the increased demands placed on the knee. A systematic review by Flanigan et al.¹ found the overall prevalence of full-thickness chondral defects in athletes to be 36%. These injuries can cause marked limitation of sporting activities and an inability to return to sports.² Osteochondritis dissecans (OCD) and chondromalacia patellae are two common conditions in adolescents affecting cartilage in the knee. OCD is a chronic condition in which a limited lesion of subchondral bone necrosis progresses toward the separation of a segment of articular cartilage and the underlying subchondral bone from the surrounding cancellous bone.³ Chondromalacia patellae involve degeneration of articular cartilage of the posterior surface of the patella. In early stages, the cartilage becomes soft, and subsequently, fissures develop resulting in cartilaginous flakes and gradual erosion of cartilage down to the subchondral bone.⁴

Cartilage has a limited capacity for repair⁵ and, when left untreated, can cause severe and progressive disability of the joint leading to osteoarthritis.⁶ Therefore, early diagnosis and treatment of chondral defects not only facilitates a quicker return to sporting activity but also decreases the risk of developing osteoarthritis. Various procedures have been described in the literature for the treatment of cartilage injuries in adolescents, ranging from fixation, osteochondral allografts transfer system (OATS), marrow stimulation techniques, and, more recently, cell-based techniques.

Fixation of osteochondral lesions with screws, pins, and rods have been described to stabilize the fragment and retain a congruent articulation.⁷,⁸ Autologous osteochondral transplant, in which a cylindrical osteochondral graft is taken from the femoral condyle and transplanted to the defect, is also well documented as a surgical treatment for chondral defects.⁹,¹⁰

Marrow stimulation techniques such as abrasion arthroplasty and microfracture are commonly used¹¹,¹²,¹³ to penetrate the subchondral bone, allowing the release of stem cells and growth factors from the bone marrow, thereby promoting cartilage repair. Steadman et al.¹⁴ showed improved symptoms, function, and activity levels in football league players with full-thickness chondral defects treated with microfracture. However, marrow stimulation has been shown to stimulate growth of fibrocartilage, which is inferior to hyaline cartilage and does not have long-term benefits.¹⁵,¹⁶,¹⁷

Interest in cell-based therapy increased and developed in the 1990s with a landmark study by Brittberg et al.¹⁸ In the study, 23 patients with full-thickness cartilage defects were treated with autologous chondrocyte implantation (ACI) and results showed regain of considerable knee function in patients with femoral defects at 3 years follow-up. Biopsies taken showed production of hyaline cartilage in 11 of 15 femoral transplants, which resembles normal articular cartilage and is superior to fibrocartilage.

Cell-based therapy broadly encompasses chondrocyte implantation and mesenchymal stem cell (MSC) implantation. It involves harvesting of chondrocytes or MSC, culturing them in the laboratory, and subsequently returning the cultured cells to the defect. In a study by Peterson et al.,¹⁹ ACI for femoral or patellar cartilage defects was associated with durable function for as long as 11 years. Another prospective cohort study showed that ACI and microfracture had significantly better results at final follow-up (mean 7.5 years) as compared to microfracture alone in a group of high-level male soccer players.²⁰ At a 3-month posttransplantation arthroscopy, Brittberg et al.¹⁸ found that transplants had the same macroscopic appearance as the surrounding cartilage. Bentley et al.²¹ also reported that second-look arthroscopy at 1 year demonstrated excellent or good functional outcomes in 82% after ACI using the Cincinnati Rating System and Stanmore Functional Rating System.

Apart from harvesting chondrocytes, MSCs can also be harvested for in vitro culture from various tissues such as bone marrow²²,²³ and adipose tissue.²⁴ Their easy availability makes harvesting simpler and reduces the problem of donor site morbidity that is a concern in ACI.

Two studies in a rabbit model and human population have demonstrated that human bone marrow is a better source of MSCs with better chondrogenic capacity than adipose tissue.²⁵,²⁶

Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown to differentiate into chondrocytes as early as 2 weeks posttransplantation²⁷ and resulted in significant arthroscopic²⁸ and clinical improvement²⁹ in patients with chondral defects. Comparisons have been made clinically between ACI and autologous BMSC implantation. In an observation cohort study led by Nejadnik et al.,³⁰ 72 matched patients (lesion and age) underwent cartilage repair using chondrocytes or BMSCs. Both groups had significant improvements in the quality of life after cartilage repair (physical and mental components of the Short Form-36 questionnaire included in the International Cartilage Repair Society [ICRS] package). There was no difference in clinical outcome except that BMSCs were better for physical role functioning, with a greater improvement over time. The study showed BMSCs to be as effective as chondrocytes while avoiding the disadvantages associated with chondrocyte implantation such as donor site morbidity from the sacrifice of healthy cartilage, pain from the site of harvest of the periosteal patch, and risks and costs of a second surgery.

BMSCs, once harvested and cultured, can be delivered into the knee joint via two general approaches: open and intra-articular. In the open technique, cultured cells may be implanted directly into the defect, or via a suitable matrix or scaffold such as collagen or fibrin, seeded with chondroprogenitor cells and signalling substances. However, these methods are invasive, requiring a second surgery for transplantation, and none has shown to be superior to the rest.³¹

To reduce the need for a second surgery, a novel technique of administering MSCs via intra-articular injections was developed and published by McIlwraith et al.²⁸ in an equine model. Improvements were seen in both arthroscopic and immunohistologic examination after the administration of intra-articular BMSCs and hyaluronic acid (HA) with microfracture when compared with HA and microfracture alone.

A study led by Lee et al.³² in a porcine model showed that the outcomes of intra-articular injections of autologous BMSCs and HA were comparable with an open technique using BMSCs implanted beneath a sutured periosteal patch over the defect. The authors’ present technique translates this intra-articular injection method to human patients to restore cartilage defects in the knee.

For adolescent patients with OCD, the indications for surgery are pain, locking, and instability. Contraindications include early osteoarthritic changes, inflammatory diseases such as rheumatoid arthritis, previous trauma or infection to the growth plate, and underlying tibial femoral malalignment. In the authors’ study on cell-based therapy in patellar OCD,³³ patients with ICRS grade 3 or 4 patellar OCD diagnosed clinically and radiographically were included.