ACI and MACI
The ultrastructure of articular cartilage is unique: chondrocytes are sparsely distributed within the surrounding matrix, maintaining minimal cell-to-cell contact. The interaction between cells, collagen framework, aggrecan, and fluid constitutes the complex ultrastructure of hyaline cartilage, making its replacement or reproduction difficult.1
New, ambitious regenerative procedures are emerging as potential therapeutic options for the treatment of chondral lesions, aiming to re-create a hyaline-like tissue, thus restoring a biologically and biomechanically valid articular surface with durable clinical results.
Autologous chondrocyte implantation (ACI) was introduced in 1987 in Sweden, and in 1994 Brittberg et al2 published the first clinical report showing satisfactory results for isolated femoral condyle lesions. Since then, several studies have followed, documenting both the production of a hyaline-like articular surface and good results in the majority of the patients at medium-long follow-up. Treatment indications have been broadened,3–5 and this cell-based technique has gained increasing interest worldwide.6–10 The development of bioengineering technology further improved this regenerative treatment approach—essentially, transplanting biodegradable molecules that are used as temporary scaffolds for the growth of living cells.11 Matrix-assisted ACI (MACI) techniques were introduced in the clinical practice one decade ago, showing good clinical results while at the same time overcoming most of the concerns related to the first-generation ACI.12 The use of cell-loaded scaffolds to regenerate a cartilage-like tissue presents advantages from both the biological and the surgical point of view, thus aiming to further optimize this regenerative surgical procedure.
Surgical Technique
The surgical technique of both ACI and MACI consists of two steps. The first one is an arthroscopic procedure in which a biopsy of healthy cartilage is harvested from a non—weight-bearing site on the articular surface (usually intercondylar notch) for autologous chondrocyte cell culture, and the second step consists of implanting the expanded chondrocytes ( Fig. 8.1 ).
The ACI procedure involves the implantation of a liquid cell culture, thus requiring the use of a flap to avoid leakage of chondrocytes from the defect area. An autologous periosteal patch has been traditionally used for its biological activity, but recently the use of a collagen xenograft membrane is becoming more popular. Through a parapatellar arthrotomy, the flap is sutured to the defect rim, and fibrin glue or sealant is applied to create a watertight seal before the cultured cells are injected.10
The bioengineered MACI technology simplified the second step, which differs depending on the scaffold used. A mini-open approach can be used to prepare the lesion site, debriding the defect area down to the subchondral bone. Afterward, using a foil template reflecting the size and geometry of the defect, the chondrocyte-loaded matrix is cut to size and fitted into the defect with the cell-loaded surface facing the subchondral bone. In the case of an arthroscopic approach, dedicated instruments are used:13 a circular area with regular margins for graft implantation is prepared with a specially designed cannulated low-profile drill. The delivery device is then filled with the bioengineered tissue, which is transported and positioned in the prepared area.
Depending on the adhesive characteristics of the grafts, no fibrin glue or sutures are needed, but for some biomaterials fibrin glue is used to fix the implant, and a transosseous fixation technique has been proposed to ensure secure fixation of the graft even in defects without stable shoulders.12,14
Rehabilitation Protocol
A similar rehabilitation protocol is used for both treatment approaches.
In the early stage (0 to 6 weeks), the rehabilitation strategies are focused on controlling pain, effusion, loss of motion, and muscle atrophy, and on protecting the transplant by preventing weight bearing for ∼ 4 weeks. Continued passive motion is usually applied intensively until 90 degrees of flexion is attained, to avoid joint adherence and favor chondral nutrition and regenerative processes. Controlled mobilization exercises with reduced range of motion, early isometric and isotonic exercises, and controlled mechanical compression are performed. In the fourth week progressive touch-down weight bearing with crutches is allowed and usually advanced to full weight bearing within 6 to 8 weeks after surgery. Gait training in a swimming pool can be prescribed to facilitate the recovery of normal gait phases. Subsequently, active functional training can be started if there are no symptoms of overloading, such as pain, effusion, and tenderness. Proprioceptive, strength and endurance exercises, and aerobic training are then introduced, aiming to return to a correct running pathway. The remainder of the rehabilitation is dedicated to the return to previous sport activity, which is usually allowed no earlier than 1 year after surgery. However, time needed to recover may vary markedly depending on the procedure used. The bio-engineered tissue significantly reduces the inherent fragility of the culture implant during the early postoperative stage and makes an accelerated patient recovery possible. The arthroscopic approach results in lower surgical morbidity and may enable a further acceleration of the functional recovery.15,16
Results
ACI
Since its conception 20 years ago, satisfactory clinical and radiographic (magnetic resonance imaging [MRI]) outcomes have been reported consistently at medium- to long-term follow-up for the ACI procedure.3–10
After the preliminary promising results,2 the indication of this treatment has been broadened, and good patient-reported outcomes have been reported also for more challenging lesions. Browne et al8 documented good results in large defects and in patients who previously failed prior cartilage repair. Minas et al4 treated patients affected by early osteoarthritis successfully. Rosenberger et al17 analyzed ACI treatment in older patients and found outcomes comparable to those reported in the literature for younger patients if all articular comorbidities were recognized and treated concomitantly. Farr18 and Pascual-Garrido et al19 showed that even more complex patellofemoral lesions can successfully be treated as long as corrective osteotomies are being performed to unload the repair tissue. The ACI procedure has also been modified to expand the treatment to deep osteochondral lesions. This “sandwich technique” procedure shows good results for the treatment of osteochondritis dissecans (OCD) at medium-term follow-up.5
Recently, Peterson et al7 investigated the 20-year outcomes of the ACI procedure with periosteum in 224 patients. The subjective scores documented a significant improvement compared with the preoperative values. Seventy-four percent of the patients reported that they were better or stable, and 92% were satisfied with the operation and would undergo the ACI again. Further analysis was performed to determine factors that could influence the final outcome. The authors found that the age at the time of the operation and the size of the lesion did not correlate with the results, and interestingly the presence of meniscal injuries before ACI or history of bone marrow procedures before the implantation did not affect the outcome in this series either. This is in contrast to a report by Minas et al, who showed a three times higher rate of failures for defects that had prior treatments affecting the subchondral bone.20 Better results have been obtained in cases of isolated femoral condyle lesions and OCD, whereas patients with multiple lesions undergo a progressive decline, with the bipolar lesions having an inferior outcome at 20 years.
These studies demonstrated that patients report good and excellent clinical and functional outcomes after ACI at long-term follow-up. With regard to imaging, encouraging data have also been documented.21 Even though intralesional osteophytes, subchondral cysts, and bone marrow edema were common, the defect area was restored in most patients, with the quality of the repair tissue being similar to the surrounding normal cartilage, thus confirming the good long-term outcome offered by this procedure.
However, these good results have to be weighed against several limitations related to the complexity and morbidity of the surgical procedure, which requires a large open surgical approach and thus entails a high risk of joint stiffness and arthrofibrosis. The periosteal patch is believed to have biological properties, but it also requires a second incision and causes a high rate of hypertrophy with a high reoperation rate.9,22–24
A much lower complication rate has been shown by several authors using a type I/III collagen membrane in place of periosteum.25,26 A further improvement of the procedure has been introduced with the development of a new technology: characterized chondrocyte implantation (CCI), which aims to improve the results of articular regeneration through the use of a selected cell population (approximately 5% deselection of inferior whole culture populations of chondrocytes).27,28
However, despite the substantial development undergone by the procedure since its introduction, some problems remain unsolved. One of those factors is the concern about the maintenance of the chondrocytic phenotype during the prolonged mono-layer culture, which is a critical factor. In fact, it is known that chondrocytes in two-dimensional cell cultures alter their pheno-type and dedifferentiate to fibroblast cells that no longer possess the capacity to produce type II collagen or proteoglycans,6 and it is still unclear whether transplanted cells re-express their phenotype after transplantation. Another important concern is whether chondrocytes will be homogeneously distributed in the three-dimensional (3D) space of the defect when used in liquid cell suspension. Even with meticulous technique, there is the risk of chondrocyte leakage.
Related posts:
Microfracture and Augments
Science and Animal Models of Marrow Stimulation for Cartilage Repair
The Cartilage–Bone Interface
Particulated Articular Cartilage: CAIS and DeNovo NT
Improved Preservation of Fresh Osteochondral Allografts for Clinical Use
Science and Animal Models of Marrow Stimulation for Cartilage Repair
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