Autologous Chondrocyte Implantation

Introduction

Historical Perspective

Autologous chondrocyte transplantation (ACT) has been known as autologous chondrocyte implantation (ACI) in North America. The technique as described by Peterson and co-workers was adapted by me after several visits to Sweden in the early 1990s ( Fig. 9.1 ). Since March 1995 after institutional review board approval in 1994, the technique of ACI was used to manage large acute and chronic focal articular cartilage injuries in knees. To date, over 1,000 treatments have been performed at our institution as of 2010, over 30,000 patients have been treated in North America with ACI. The exact number of ACI transplantations worldwide is unknown due to a growing number of cell companies, including JTEC in Japan, Co.Don (ChondroSphere), B. Braun/Aesculap (NovoCart 3D) in Germany, Fidia/FAB (HyaloGraft-C) in Italy, and Tigenix (ChondroCelect) in the Benelux region.

Fig. 9.1, Classic technique for autologous chondrocyte implantation (ACI). (A) Arthroscopic evaluation of the knee joint and identification of a full-thickness medial femoral condyle injury. A cartilage biopsy is taken from the superior intercondylar notch, digested, and cultured. Autologous chondrocyte transplantation will occur when the cells have reached a volume that can fill the articular cartilage defect. (B) A two-incision approach is made to the knee. The first is a medial arthrotomy to expose the full-thickness medial femoral condyle defect. The second is an incision distal to the pes anserinus tendon insertion to harvest periosteum templated exactly to the defect after it is debrided. (C) The technique of ACI. A periosteal patch is harvested distal to the pes anserinus tendons. It is microsutured with interrupted 6.0 Vicryl sutures flush to the articular surface and tested for water integrity tightness. It is then sealed with fibrin glue to maintain water tightness. The autologous chondrocyte suspension is injected deep to the periosteal cover to fill the defect and the opening is sutured over and sealed with fibrin glue. The knee joint is closed. The patient undergoes careful rehabilitation to restore motion and allow the graft to mature uneventfully.

The use of autologous chondrocytes for patient care in the United States has been carefully regulated by the Food and Drug Administration (FDA, Biologics Division) and since its introduction it has required both good laboratory practices (GLP standards) and good manufacturing practices (GMP standards). These industry standards have conseqently restricted the use of ACI to private and academic institutions. As of August 22, 1997, the FDA formally approved ACI (FDA Biologics License 1233) for the management of focal chondral defects of the femoral articular surfaces. This was based on the 1997 data of 159 patients evaluated in Sweden. Because of the early results that were unfavorable for management of the patella, tibia, or cases involving early bipolar or arthritic lesions, these defects have been considered “off-label.” However, prior to FDA approval, I had gained considerable experience in the treatment of these “off-label” uses based upon patients who were sent for management of these troublesome lesions.

In my experience, the patient who is highly motivated, realistic regarding the rehabilitation protocol, is a nonsmoker, and is not using narcotics for pain management is desirable. A strong social support system and a sense of vitality as measured by the Short Form 36 has proven to be a high statistical predictor of a good physical outcome in a study conducted at our institution and presented at the International Cartilage Repair Society in Toronto, Canada, in 2001. Patients under the age of 18 years also have an excellent chance of returning to full activities.

This chapter will discuss the role of ACI for the treatment of full-thickness cartilage injuries in knees. Since the initial publication on this topic, there has been a renewed interest in treatment and research of this clinical problem. The earlier published study indicated good and excellent results in 14 of 16 patients treated on weight-bearing femoral condyles. Only 2 of 7 patients with patellar lesions treated had similar results.

Indications

The initial early indication for ACI was for a symptomatic full-thickness weight-bearing chondral injury of the femoral articular surface in a physiologically young patient who was compliant with the rehabilitation protocol. The results of chondral injuries for the patellofemoral joint were not as consistently high as those of the femoral weight-bearing condyles. Patients with osteochondritis dissecans (OCD) have also done well. The ideal indication for ACI is for treatment of a symptomatic unipolar grade III or grade IV Outerbridge classification injury, with no greater than the reciprocal articular surface having grade I to II Outerbridge classification chondromalacia.

However, these injuries are uncommon. Curl in his classic review of 31,516 knee arthroscopies found that the incidence of an isolated femoral condyle defect in patients under 40 years old was less than 5%. However, the incidence of articular cartilage injuries throughout the knee was almost 60%. This has also been my experience.

Because of the heterogeneous nature of articular cartilage defects found in the knee arthroscopies that are symptomatic, yet focal in nature, I elected to classify the treatments early on in relatively homogeneous groups. The classification was Simple, Complex, and Salvage.

Simple: An isolated grade 3 or 4 Outerbridge weight-bearing femoral condyle defect in a neutrally aligned knee that is stable with an intact meniscus.

Complex: Isolated or multiple grade 3 or 4 Outerbridge chondral defect(s) is(are) on any surface within the knee joint. As in the case of unipolar lesions, background factors may need to be corrected either prior to or at the time of the cartilage surgery.

Salvage: These patients have early osteoarthritic lesions. Radiographically there may be early joint space narrowing and intralesional or peripheral osteophyte formation. Arthroscopically, bipolar lesions may be present in the patella–trochlea or tibia–femur and generalized chondromalacia may be present. The lesions may be peripherally uncontained.

As of June 2009, 550 transplants had been performed in 500 patients (simple 35; complex 22; salvage 294). In my series, simple cases only accounted for 35 of 550 treatments (6.4%).

The management of the larger group of patients in the complex and salvage category treatments have resulted in excellent clinical outcomes despite the heterogeneous nature of the cartilage injuries.

For this reason, my approach to treating young patients who are disabled with pain and poor function involves a careful assessment of long leg alignment x-ray images, a well-preserved weight-bearing joint space or early joint space narrowing, magnetic resonance imaging (MRI) scan or arthroscopic evidence of focal acute or chronic articular cartilage injury. If the lesions are focal in nature when assessed arthroscopically with identifiable borders and reasonable cartilage thickness, I consider the patient for ACI if it appears that the patient’s symptoms relate to the areas of chondral damage. A cartilage biopsy is then performed, and the cells are cultured, cryopreserved, and stored awaiting second-stage implantation.

At the first postoperative visit, the proposed reconstructive surgery is discussed with the patient and the background factors that need to be corrected are addressed in addition to the transplantation to the focal articular cartilage defects. The individualized surgery, hospitalization, and rehabilitation are also discussed. The potential postoperative risk of stiffness and its management are discussed. At this visit an assessment is made of the patient’s proposed goals at final clinical outcome. If the goals are unrealistic, they are further discussed with the patient and realistic expectations are set. We do not proceed with surgery if the patient remains on baseline narcotics or is a smoker or there is a concern about the patient’s emotional well-being. When these issues are resolved, we can proceed with the recommended reconstruction.

Arthroscopic Assessment and Cartilage Biopsy for Cell Culturing

Arthroscopic assessment of the joint and possible biopsy for articular cartilage culturing requires a careful and systematic evaluation of the articular surfaces with an arthroscopic probe to demonstrate and determine the extent of grade III and IV chondromalacia (CM) of the symptomatic lesion. The opposing tibial articular surface must be probed throughout to ensure that the meniscus is intact, the articular surface is healthy, and with chondromalacia ideally no greater than superficial fissuring (Grade II CM), otherwise it may also be considered for repair if the radiographic joint space is intact and the defect rim healthy ( Fig. 9.2 ). The femoral condyle lesion should be assessed for its anterior to posterior length and whether it is a contained or an uncontained lesion. The quality and thickness of the surrounding articular cartilage should also be assessed. This will determine whether healthy cartilage will be available for periosteum or collagen membrane suturing or whether an uncontained chondral injury will require suturing through synovium or small drill holes through the bone (see Fig. 9.21 technique on uncontained defects). The posterior extent of the lesion is critical and must be technically accessed at the time of open arthrotomy for periosteal suturing.

$Fig. 9.2, Arthroscopic knee joint evaluation. (A) A focal area of cartilage damage is identified on the lateral femoral condyle. (B) The tibial plateau is carefully probed to ensure that it is intact. (C) The meniscus is also probed to ensure that it is intact. Some superficial Outerbridge grade II changes to the lateral tibial plateau are seen but are of no consequence. (D) The chondral injury is carefully probed to identify that there is only a superficial fibrous tissue cover over a large intralesional osteophyte that has developed following a previous microfracture to the lateral femoral condyle. This patient is a candidate for autologous chondrocyte implantation (ACI). (E) Another patient with arthroscopic evaluation of the patellofemoral joint. A large grade 4 defect of the patella is noted with intact margins. The trochlea has Outerbridge grade II superficial changes. Various lateral maltracking of the patella. The patient is a good candidate for ACI to the patella with tibial tubercle anteromedialization. (F) A long focal grade 4 defect of the trochlea is 4 cm long and 1 cm wide. This patient is also a candidate for ACI.$

If a lesion is considered appropriate, a biopsy site for cartilage procurement must be decided upon ( Fig. 9.3 ). In Europe, the most commonly chosen site for biopsy is the superior medial edge of the trochlea, adjacent to the medial patella (odd) facet ( Fig. 9.4 ). In this way, a biopsy site will not be producing a reciprocal symptomatic injury because there will be no opposing articular surface to make its contact. The patellofemoral joint must be assessed carefully. If there is an overhanging patellar facet on the medial side, the superior lateral facet may be harvested. My preferred location is the superior and lateral intercondylar notch because it is convenient and known not to create problems when removed as per anterior cruciate ligament (ACL) reconstruction ( Fig. 9.5 ). Finally, either the superior transverse trochlea margin adjacent to the supracondylar synovium or the distal lateral trochlea at the sulcus terminalis are potential biopsy sites. At the time of open implantation, the synovium may be advanced over the biopsy site via sutures through the articular cartilage.

Fig. 9.3, Arthroscopic biopsy sites for autologous chondrocyte implantation (ACI). (A) Possible locations for biopsy performed for ACI. Dotted lines represent the leading weight-bearing surfaces of the femoral condyles, the sulcus terminalis both medial and lateral. Cartilage biopsies should be taken from the margins of the trochlea just proximal to the weight-bearing surfaces. When the intercondylar notch is harvested, the biopsy is taken from the superior surface to the sulcus terminalis on the lateral wall. (B) The superior portion of the trochlea on the medial corner can also be used when all other sites are not appropriate.

Fig. 9.4, Classic location for harvest of cartilage for autologous chondrocyte implantation is the superior medial corner of the trochlea adjacent to the odd facet of the patella in a nonarticulating margin. However, when the medial patellar facet overhangs this margin, another location with no engagement of the patella should be found. The distal lateral trochlea proximal to the sulcus terminalis can frequently be used.

Fig. 9.5, Surgical technique for harvesting articular cartilage from the intercondylar notch. (A) Diagrammatic representation of the use of a sharp small gouge for scoring the articular cartilage from the superior intercondylar notch to the sulcus terminalis on the lateral wall. (B) All layers of cartilage down to bone should be harvested to take representative articular cartilage layers using a side-to-side whittling motion. (C) The defect left behind measures approximately 5 mm wide by 1 to 1.5 cm long. The full-thickness articular cartilage (usually 200–300 mg) is adequate for cell culture and expansion. It represents a non-weight-bearing portion when the knee is brought into full extension and visualized. (D) Arthroscopic appearance of the intercondylar notch at the time of biopsy in the left knee. Scoring of the articular cartilage to ensure that the gouge does not stray when pressure is applied to harvest cartilage. (E) The gouge is started at the 11 o’clock position in a whittling manner. Full-thickness cartilage is engaged down to bone. (F) The cartilage is left intact as it is brought to the lateral side of the intercondylar notch. (G) The cartilage is left attached at its distal-most attachment site at the sulcus terminalis of the lateral femoral condyle. (H) It is then grasped with a grasper and brought out of the medial arthroscopic portal as one piece. (I) In full extension, no impingement of the cartilage is seen on the tibial spines or the weight-bearing surfaces.

Approximately 200–300 mg of articular cartilage are required for enzymatic digestion for cell culturing, which corresponds approximately to a cartilage surface of 5 mm wide by 1 cm in length. This contains approximately 200,000–300,000 cells, which may be enzymatically digested and grown to approximately 12 million cells per 0.4 cc of culture media per implantation vial.

Biopsy instruments may include ring curette or sharp gouges. It is often helpful to incise and score the area of biopsy before attempting to remove it. A whittling, side-to-side motion of the gouge or curette will then more accurately remove the desired cartilage without an unwanted slip. Full-thickness cartilage down to bone should be biopsied. It is helpful to leave an end of the articular biopsy attached so that it may be grasped with an arthroscopic grasper and torn off. This avoids an unwanted loose body in the joint, which then must be captured. Following in vitro expansion of cells 3–5 weeks later, a suitable number and volume of cells will be grown to accommodate the defect size that is required. At this time, second-stage open implantation may occur.

Surgical Correction of Background Factors Predisposing to Chondral Injury

Several predisposing factors to chondral injury must be assessed so that these may be either corrected in a staged or concomitant fashion with ACI. Tibial femoral malalignment, patellofemoral malalignment, and ligamentous, meniscal, or bone insufficiency must be assessed prior to definitive cartilage cell re-implantation.

Long leg alignment is assessed in all patients (as noted in Chapter 3 ) with double leg stance long alignment digital x-ray images to include hip, knee, and ankle for varus and valgus mechanical alignment assessment (clinical examination is notoriously unreliable for long leg alignment).

Patellofemoral alignment is assessed by clinical examination with localization of the tibial tubercle, determining the quadriceps angle measured with the patella in the reduced position in the trochlea, the presence of a J-sign as the patella relocates from the extended into the flexed position, and the absence or presence of crepitus of the patella with active extension of the knee. If the patient is overweight and the clinical examination is difficult, a computed tomography (CT) scan is performed with the knee in extension first with the quadriceps in the relaxed and then contracted position to assess patellofemoral subluxation ( Chapter 8 ). Dye can be added within the joint to localize and measure the chondral defect(s) in the patella, trochlea, or both.

A clinical examination is best for ligamentous instability unless the patient is very muscular or obese, in which case an MRI scan may be necessary or an examination under anesthesia.

Meniscal insufficiency is difficult to quantify with an MRI scan unless the meniscus is completely absent. An arthroscopic assessment is best performed to assess the status of the meniscus and the residual hoop stress capability at the time of the arthroscopy for the cartilage biopsy for cell transplantation.

Although arthroscopy is helpful in assessing the depth and character of an osteochondral defect, CT scan is usually more useful to determine whether there are subchondral bony cysts present that cannot be visualized at the time of arthroscopy. This will help in addressing whether isolated ACI can be performed for an osteochondritis dissecans lesion or whether autologous bone grafting is necessary into a staged or single step sandwich technique ACI.

These techniques will be discussed after the technique of open surgical transplantation of autologous chondrocytes is reviewed in the case of an ideal lesion suitable for transplantation.

Surgical Implantation of Autologous Chondrocytes

The steps in open implantation include arthrotomy, defect preparation, periosteum procurement, periosteum fixation, periosteum watertight integrity testing, autologous fibrin glue sealant, chondrocyte implantation, wound closure, and rehabilitation.

For a unicondylar injury, a medial or lateral parapatellar arthrotomy is utilized, which is usually done through a midline skin incision or a longitudinal parapatellar incision. Adequate exposure is crucial to good suturing technique of periosteum and several retractors are often required to achieve it. Posterior lesions on the femur will often require hyperflexion of the knee and occasional takedown of the meniscus in a subperiosteal fashion with intermeniscal ligament takedown and coronary ligament release of the tibia as the meniscus is peeled back with the entire sleeve of tissue ( Fig. 9.6 ). A repair of these is undertaken during closure. For multiple lesions, a traditional medial parapatellar arthrotomy is often required with subluxation or dislocation and eversion of the patella with hyperflexion.

Fig. 9.6, Deep dissection of a medial or lateral arthrotomy to obtain exposure to the posterior medial femoral condyle or tibial plateau, or a lateral femoral condyle and lateral tibial plateau. (A) Frontal view demonstrating a medial femoral condyle defect that is posterior or a central or posterior medial tibial plateau defect. The intermeniscal ligament is taken down and the coronary meniscal attachment on the tibia is taken down to the medial meniscus. The entire soft tissue sleeve is dissected posteriorly so that it is continuous and deep to the superficial medial collateral ligaments. By hyperflexing and externally rotating the tibia, the tibial plateau can be delivered almost entirely or the medial femoral condyle posteriorly. (B) Superior view of a posterior tibial plateau chondral defect in relation to the intermeniscal ligament and the meniscus and superficial and deep medial collateral ligaments. (C) If the medial sleeve is taken down in a posterior direction off the tibia to expose the posterior tibial plateau but is still too tight, a bone block attachment to the femoral condyle origin of the medial collateral ligament will allow the entire medial side of the knee to be opened quite easily. It is then reattached with a screw and washer fixation at the end of the procedure. I have found that this is rarely required. (D) Frontal view of the lateral femoral condyle and lateral tibial plateau after dissection of a lateral sleeve of meniscus, coronary ligament, and portion of the iliotibial band insertion to gain exposure to the posterior lateral femoral condyles or lateral tibial plateau. (E) View of the lateral tibial plateau cartilage defect from above, with structures intact. (F) Superior view after release of the intermeniscal ligament and coronary ligament with lateral meniscus takedown of a lateral soft tissue subperiosteal sleeve. Upon completion of autologous chondrocyte implantation, the origins of the anterior horns of the medial or lateral menisci are reattached to their native positions using transosseous Ethibond sutures.

If the chondral defect is lateral, obtaining access to a posterior lesion is frequently difficult if the tibial tubercle is laterally positioned on the tibia. In this case a tibial tubercle osteotomy (TTO) and elevation is very helpful for exposing the lesion and realigning the extensor mechanism centrally (see section “ACI plus TTO for Posterior Exposure/with Patella/Trochlea ACI”). This will often allow a very posterior exposure to the femoral condyles without taking down the intermeniscal ligament with the meniscus and coronary ligament off the tibia.

Defect preparation is critical. Radical debridement of all fissured and undermined articular cartilage surrounding the full thickness chondral injury to healthy contained cartilage is desirable. Early failures occurred from inadequate debridement with poor integration to adjacent cartilage with either progression of disease in the adjacent non-debrided fissured cartilage or delamination of the repair tissue from the damaged native tissue. Oval or curvilinear excisions with a no. 15 blade are made by incising the articular cartilage vertically down to the subchondral bone plate without penetrating the bone. Small ring or closed curettes and periosteal elevators are used to debride the degenerating articular cartilage back to healthy host cartilage. Maintaining an intact subchondral bone plate without subchondral bone bleeding is important. It is essential not to perforate the subchondral bone plate such that a mixed marrow cell population does not populate the chondral defect in addition to the end-differentiated chondrocytes that have been grown in vitro. A contained lesion is desired and it is better to leave a minimally chondromalacic cartilage border than to remove the border and leave an uncontained lesion that would require suturing to synovium or micro-holes through bone drills ( Fig. 9.7 ). Once a healthy defect bed is prepared, it is measured in its length and width, or if it is irregularly shaped, templated with sterile tracing paper (sterile glove packaging paper works well). A sterile marker can be used to template the defect and it can then be cut out to fit the defect perfectly. It can be oversized by approximately 2 mm in both length and width on the periosteal site when it is prepared (the periosteum shrinks as it is procured). Alternatively, this can be measured and marked with a marker directly onto the periosteum if it is an uncomplicated shape and cut directly ( Fig. 9.8 ).

Fig. 9.7, Transosseous drill hole fixation for uncontained cartilage defects. A large uncontained lateral trochlear defect is demonstrated. Radical debridement of the cartilage is performed. Any sclerotic bone is removed with a sharp ring curette and possibly deepened with a high-speed bur if the bone is very sclerotic, leaving a prominent peripheral margin intact. Transosseous drill holes through the margin then allow a cavity to be formed. A small P1 cutting needle is straightened out with two heavy needle drivers. The sutures are transfixed through the membrane and the drill holes to maintain a peripheral seal to the defect. This is reinforced with fibrin glue sealant around the uncontained margins, checked for water tightness, and then injected with autologous cultured chondrocytes once the defect margins are secured and watertight.

Fig. 9.8, Periosteal harvest. (A) Paper template is applied distal to pes anserinus tendons on the subcutaneous medial border of the tibia onto the periosteum directly. It is sharply oversized by 1 mm circumferentially using a no. 15 blade. (B) A small sharp periosteal elevator is used to remove the entire periosteal membrane from the bone, maintaining the deep cambium layer orientation. The superficial fibrous layer is marked with a sterile marking pen to ensure this orientation.

If there is subchondral thickening, sclerosis or intralesional osteophyte formation at the base of the chondral defect from prior marrow stimulation technique (drilling, abrasion, microfracture), it should be taken down to the level of native subchondral bone. This can be performed with a rongeur and a high-speed bur (usually 5-mm diameter) to the level of the native subchondral bone ( Fig. 9.9 ). This will provide a cavity for the cell suspension that is injected underneath the membrane cover and will lessen the stiffness of the subchondral bone so that the newly forming cartilage repair tissue will integrate to form a new osteochondral unit with a viscoelastic cartilage surface, a subchondral bone plate that is not overly stiff to cause premature degeneration of the tissue and a normal subchondral cancellous bone. Surprisingly this thickened and calloused bone does not bleed when a tourniquet is let down. In fact, if bleeding does occur, it is usually scant and is easily managed with a thrombin epinephrine-soaked neural patty or a drop of fibrin glue and occasionally a fine-tipped electrocautery is used.

$Fig. 9.9, Takedown of sclerotic bone/intralesional osteophytes. (A) Intralesional osteophytes may form after marrow stimulation techniques (abrasion, drilling, microfracture) or from idiopathic osteoarthritis. (B) A 5-mm high-speed bur is used under irrigation to gently take down this sclerotic cortical type bone to the level of the adjacent native subchondral bone. (C) When the tourniquet is let down, little bleeding occurs from these sites. Autologous chondrocyte implantation (ACI) may then be performed safely on a chondral defect whose depth has not been taken up by bone. Whether this technique will improve the results of ACI after marrow stimulation techniques is unknown.$

Thickening and sclerosis of the subchondral bone is also found in cases of early osteoarthritis with chronic articular chondral defects. In these cases, the surrounding cartilage is often thinned and the periphery of the defect is marginally uncontained. A contained defect can be made by using a high-speed bur to deepen the area of bony exposure to the level of more normal subchondral bone and provide a cavity for the cartilaginous tissue repair by using transosseous drill holes around the periphery to anchor the membrane. This has been my method of repair in patients frequently seen in the salvage category of treatment.

The easiest and most suitable location for periosteum procurement is from the proximal medial tibia, distal to the pes anserinus insertion on the subcutaneous border. At this site there is a very thin fascial layer of subcutaneous fat and the periosteum is easily accessed. Once defect size has been assessed and templated, a second incision is made approximately a finger breath distal to the pes anserinus insertion, in the center of the medial subcutaneous border of the tibia. Subcutaneous fat is incised initially and then scissor dissection will reveal the shiny white proximal tibial periosteum. It is useful to use a wet sponge to sweep away loose areolar tissue. Electrocautery should not be used because it will necrose the periosteum with the very sensitive cambium layer of cells on its deep surface.

The template is then placed on the periosteum or it is marked with a ruler and a sterile marking pen. A sharp no. 15 blade is then used to incise sharply, oversizing the periosteum 1 mm in all directions down to bone. A small sharp periosteal elevator is useful in very gently advancing the periosteum from its bony bed and preventing it from under-rolling so that it does not rip. Nontoothed forceps will help to pull the periosteum upward as it is gently removed from the tibia. A gentle push/pull type of motion of the periosteal elevator from side-to-side across the periosteum will help its removal. Mark the outside of the periosteum so that it is not inadvertently placed upside down. This marks the superficial surface.

At this time the defect site is inspected and the tourniquet can be either let down to assess bleeding of the subchondral bone plate or let down at the end of the procedure if the surgeon is confident that the bone bed appears not to be violated. If there is any bleeding of the bony bed, it can usually be stopped by using a combination of thrombin and epinephrine soaked in a neural patty applied to the defect and gently pressed for several minutes. Upon removal, if there continues to be some bleeding, a small drop of fibrin glue will usually suffice to make the defect dry.

The goals of periosteum or collagen membrane fixation are threefold: first, to provide a watertight membrane that acts as a mechanical seal; second, to act as a semipermeable membrane for intra-articular synovial nutrition to chondrocytes; and last, to maintain a viable periosteal cambium layer of cells so that interactive growth factors between chondrocytes and periosteum may enhance chondrocyte growth. These factors have been isolated to include TGF-beta, IGF, IL-2, and IL-6 and have been found to enhance chondrocyte colony formation when separated from periosteum and delivered directly to chondrocytes in suspension. To this end, it is important to handle the periosteum delicately so that it is not perforated and to keep it moist so that it does not undergo shrinkage or cambium cell death. Its orientation is always maintained so that a cambium layer is facing in toward the subchondral bone plate as noted by a pen mark on the superficial aspect.

Periosteum may then be placed gently onto the defect in the appropriate orientation. Nontoothed forceps are used to handle the periosteum by its edges only. Suturing is usually done with a 6.0 Vicryl suture on a P-1 cutting needle that has been immersed in sterile mineral oil or glycerin. Approximately 8” of length is usually adequate and the remainder of the suture is cut and discarded. Suturing is done in an interrupted and alternating fashion. Sutures are placed through the periosteum and then the articular surface, the knots being tied on the side of the periosteum such that they remain below the level of the adjacent cartilage to avoid unraveling with motion and to evert the periosteal edge so that it may act as a washer seal on the edge of the vertical articular cartilage defect ( Fig. 9.10 ). Hence, a watertight seal can be obtained by suture technique alone in most cases. When suturing corners, the action is like tightening a drum skin. In this way the patch is tensioned adequately throughout the entire defect and the most superior aspect of the periosteal patch is left open to accept saline and to check edge integrity and chondrocytes. Interval sutures of approximately 3–6 mm are made and these protrude through the articular surface by at least 3 mm.

Fig. 9.10, Suturing techniques for large femoral condylar defects. (A) Example of good suturing technique for a cartilage defect. The suture is placed through the periosteum and then the cartilage to obtain a good purchase of both tissues. The knot is tied on the side of the periosteum to evert the periosteum flush to the cartilage side wall and make it watertight, like a washer. In this way, the suture is also below the level of the articular cartilage and is less likely to unravel once the knee starts to undergo motion. The membrane is flush with the articular surface and forms a cavity or bioactive chamber for the cells to grow to the limiting surface membrane. (B) For long femoral condylar defects in the anterior to posterior direction, suturing technique is important to maintain a uniform cavity throughout the length of the defect. If medial to lateral suturing is not performed through the length of the defect from anterior to posterior, the membrane may bottom out on the center aspect of the length of the curve. This site is more likely to undergo premature breakdown. (C) If the periosteal or collagen membrane is oversized in the anterior to posterior direction, suturing is started at the center of the defect in a medial to lateral direction, and then anterior to posterior. The chamber cavity will maintain a uniform depth and will more likely undergo full, even cartilage fill for the length of the defect.

Periosteum watertight integrity testing is assessed by using a plastic 18-gauge 2” angiocath with a tuberculin syringe filled with saline. This step is usually avoided when a collagen membrane cover is utilized because it tends to displace the cell suspension from being absorbed to the collagen membrane, which is the desired effect. The angiocath is placed deep to the periosteum into the defect and by gently filling the defect with saline. A meniscus should rise to the opening if the defect is watertight. Any leakage can easily be seen around the perimeter of the repair site. An additional suture may be required to aid in obtaining water integrity. The saline is then aspirated from the defect and if water integrity cannot be obtained simply by suture technique, a fibrin sealant is used.

For autologous fibrin sealant, the patient must donate 1 unit of whole blood preoperatively. This is then spun off for a pack of red blood cells and a supernatant, which is concentrated to produce cryoprecipitate by a double-spin freeze–thaw technique. This takes some 14 days of preparation prior to surgery. Following double freeze–thaw technique, a concentration of approximately of 80–100 mg/dL fibrinogen can be obtained. The fibrinogen or cryoprecipitate is activated with bovine thrombin and calcium. A double-barreled syringe is required. One barrel contains the cryoprecipitate and the other barrel contains a 50/50 admixture of 10% calcium chloride and a super concentrated bovine thrombin. Fibrinogen is cleaved into active fibrin, which is deposited along the margins of the defect to seal them. Tisseel (Tisseel, Baxter Biosurgery, Deerfield, IL) is made from pooled human serum and is commercially available in Europe and the United States.

After sealing, the defect water integrity is once more tested. The angiocath is useful underneath the periosteum to ensure that the periosteum is not inadvertently sealed to the subchondral bone. The saline is aspirated from the defect bed and the defect is now ready to accept chondrocyte implantation. The chondrocyte suspension is then sterilely aspirated in a tuberculin syringe through an 18-gauge or larger needle (smaller gauges will damage the cells); the needle is then removed and switched to a flexible 18-gauge 2” angiocath. The cells are then very gently delivered through the superior opening of the periosteal defect margin to the base of the defect. As the angiocath is withdrawn, cues are injected until a meniscus comes to the surface. When the defect is filled with cells, several sutures are used to close the defect and it is then sealed with fibrin glue.

The procedure is now complete. Drains are not generally used within the joint to avoid damaging the periosteal patch or sucking the cells from the defect. When drains are needed, it should be without suction. The wound is then closed in layers and a soft dressing applied to the knee.

Advanced Techniques for Surgical Transplantation of Autologous Chondrocytes

Exposures: Outline

Posterior Femoral Lesions and Tibial Plateaus

When attempting to approach a femoral condyle lesion that is very posterior or a tibial plateau lesion, a takedown of a soft tissue envelope to varying degrees may be necessary. This involves incising the intermeniscal ligament followed by the coronary ligament attachment to the tibial plateau with a subperiosteal peel off the tibia and in a posterior direction. It is easier to perform on the medial side with a long sleeve of medial retinaculum to the deep portion of the medial collateral ligament in the mid coronal plane. This is usually enough to access a posterior medial femoral condyle. However, to get to the midportion of the medial tibial plateau or the posterior portion, two options are available. The deep medial collateral ligament (MCL) may be further taken off in a continuous sleeve with the anterior portion until the entire tibial plateau is delivered anteriorly by externally rotating the tibia and hyperflexing the knee. At closure, transosseous sutures with no. 2 Ethibond are used to reattach the sleeve of tissue in its original position. This is relatively easy when the sutures are passed almost at the level of the joint where the metaphyseal bone is softer and the suture needle may pass directly through the bone in one easy passage. The anterior horn of the medial meniscus is then reattached using transosseous sutures to its original position. The intermeniscal ligament is repaired. The other option is to take down the origin of the medial collateral ligament with a bone block off the femoral condyles, which completely opens up the medial side of the knee. I have found that this is rarely necessary and that the first option is preferable unless a very posterior medial tibial plateau requires suturing ( Fig. 9.11 ).

Fig. 9.11, Case example demonstrating exposure to posterior weight-bearing condyles and tibial plateau. (A) Weight-bearing x-ray film of a young woman involved in a motor vehicle accident who had intractable global joint pain. Her joint spaces are normal and her ligamentous examination intact. Clinical examination revealed that she has tricompartmental crepitus and joint effusions. (B) Lateral x-ray film demonstrating intact patellofemoral and tibiofemoral joints. (C) Intact skyline view of cartilage spaces. (D) Medial parapatellar arthrotomy is performed with a patellar eversion and a medial subperiosteal peel maintains the entire medial sleeve intact. This method gives excellent exposure to all the articulations, including the tibial plateau immediately in the posterior medial femoral condyles. (E) After radical debridement of the articular cartilage injuries back to intact stable cartilage, focal defects are delineated, templated, and measured. (F) Periosteal harvest from the medial subcutaneous border of the tibia is performed. The defects are microsutured, sealed with fibrin glue, and injected with autologous cultured chondrocytes. Ten years later the patient remains free of pain and discomfort and maintains normal joint spaces radiographically.

Approaching the lateral tibial plateau or posterior lateral condyles is often more difficult. A lateral parapatellar arthrotomy is performed. The intrameniscal ligament is released and the coronary ligament with the anterior horn of the lateral meniscus is peeled subperiosteally with the sleeve, which will often include some of the attachment of the iliotibial band insertion at Gerdes tubercle. The patella is subluxed into the medial parapatellar gutter and the knee is hyperflexed and internally rotated. This will usually reveal the lateral tibial plateau quite well and expose the posterior lateral femoral condyles. If the knee is stiff and there is a very laterally positioned tibial tubercle insertion, it might still not be possible. In this situation a tibial tubercle osteotomy with a subvastus lateral arthrotomy is recommended, which will easily expose the distal lateral femoral condyles and the entire tibial plateau. The meniscus may still need to be taken down and reapproximated after dealing with a tibial plateau injury ( Fig. 9.12 , with distal femoral varus osteotomy).

Fig. 9.12, Case example demonstrating exposure for osteoarthritic lesions with varus malalignment requiring open-wedge tibial valgus-producing osteotomy. (A) Open appearance of the right knee of a 48-year-old male football coach with intractable medial and anterior joint pain and effusions. A midline incision with a medial parapatellar arthrotomy is performed. The incision is continued distally and subcutaneously to the pes anserinus tendons. (B) Careful radical debridement of the joint is the most important step in the early arthritic knee undergoing autologous chondrocyte implantation. Note that a lateral intercondylar notchplasty has been performed to prevent impingement of the anterior cruciate ligament when the knee is placed into valgus. Radical debridement of the medial femoral condyle defect preserves the intercondylar osteophytes, which will be used for transosseous suture fixation of periosteum. Intralesional osteophytes are carefully taken down to increase the depth of the chondral defect to maintain a cavity throughout its entire length. (C) Periosteal microsuturing is performed throughout the length of the medial femoral condyle and the trochlear defects. Note that the final appearance of the joint appears much healthier than the initial appearance. The tibial osteotomy can easily be performed through this single midline incision after the periosteum has been harvested. (D) The periosteum on the patella is sutured by starting at the midline ridge proximal to distal to maintain the tent-like shape of the periosteum. (E) Radiographic appearance of the knee 4 years later when the patient returned for treatment of his other knee, which had become as painful as the right knee had been. He has had no pain in his right knee and he was able to return to coaching and running on the sidelines until his left knee became painful. The left knee was treated in the same way with excellent clinical outcome.

ACI Plus High Tibial Osteotomy, High Tibial Osteotomy Plus Tibial Tubercle Osteotomy, Distal Femoral Varus Osteotomy

When varus or valgus malalignment is concomitant with a medial or lateral condyle injury respectively, a corrective osteotomy is paramount to the success of the ACI. This can be done in either a staged or concomitant fashion. My preference is to do the procedure all at once. A single longitudinal incision will obtain the exposure for both procedures quite easily. However, it is imperative that if it is done concomitantly, a stable fixation must be obtained at the time of osteotomy surgery so that continuous passive motion (CPM) and early active range of motion may be pursued immediately postoperatively. Otherwise, a staged reconstruction should be performed.

A common wear pattern is a varus knee with a medial femoral condyle lesion or in combination with a trochlea or patellar injury. If there is a medial femoral condyle defect with a varus knee, a longitudinal incision is made from the superior medial pole of the patella longitudinally and distally to the inferior aspect of the tibial tubercle ( Fig. 9.13 ). A medial parapatellar arthrotomy is then performed, the defect is debrided and templated, the template is applied to the periosteum that has been exposed distal to the past anserinus tendons and periosteum harvested. Takedown of the pes tendons and superficial MCL is then performed in preparation for the tibial valgus-producing osteotomy (see Chapter 10 ). The osteotomy is then performed and fixated. The tourniquet is let down and any bleeders in the soft tissue envelope or the subchondral bone plate of the area to be transplanted are dealt with. Careful suturing and transplantation to the medial femoral condyle is then performed.

Fig. 9.13, Case example of a 19-year-old woman with a twisting work-related injury to the lateral compartment of her right knee. Fat-suppressed images include (A) a coronal magnetic resonance imaging (MRI) scan and (B) a sagittal MRI scan demonstrating bone marrow edema under the lateral tibial plateau with full-thickness articular cartilage loss to the lateral tibial plateau with an intact femoral surface and meniscus. (C) Long alignment weight-bearing x-ray films demonstrate valgus malalignment of the right knee with mechanical axis to the lateral tibial spine and 3 degrees of mechanical valgus. (D) Varus-producing femoral osteotomy and lateral tibial plateau autologous chondrocyte implantation (ACI) are performed through a longitudinal incision just to the lateral border of the patella and tibial tubercle. A lateral parapatellar arthrotomy is performed and the intermeniscal ligament is incised. A lateral subperiosteal peel, which includes the coronary ligament of the lateral meniscus and a portion of the iliotibial band, is performed to the posterior lateral corner of the tibia at the popliteus hiatus of the lateral meniscus. The patella is subluxed into the medial parapatellar gutter, the knee is hyperflexed, and the tibia is internally rotated to deliver the lateral tibial plateau. This technique gives excellent exposure to the entire lateral tibial plateau. Through the same incision proximally the quadriceps is split between the vastus lateralis and the rectus intermedius muscles. The vastus lateralis is dissected laterally to the posterior lateral corner of the femur and the linea aspera. A femoral varus-producing osteotomy is performed through the same dissection, which is an extensile Henry approach to the knee. (E) Radical debridement of the chondral defect of the lateral tibial plateau exposes its margins circumferentially. (F) The ACI graft is microsutured and its margins are sealed with fibrin glue. A single suture is left long laterally to allow injection of the autologous chondrocyte suspension and is easily closed and sealed. (G) Final radiographic appearance after femoral varus-producing osteotomy with lateral tibial plateau ACI graft.

If arthroscopy revealed maltracking of the patella in addition to a chondral defect, a TTO is performed with a medial subvastus and lateral subvastus arthrotomy elevating the extensor mechanism proximally. The defects are debrided, the periosteum is harvested, the tibial valgus osteotomy is performed and fixated (see Chapter 10 , combined osteotomies). The periosteal covers are then microsutured and transplanted. The tibial tubercle is repositioned and centered to normalize the extensor mechanism forces postoperatively.

ACI Plus Tibial Tubercle Osteotomy for Posterior Exposure/With Patella/Trochlea ACI

Patellofemoral maltracking combined with a trochlea or patellar chondral injury requires careful preoperative assessment with physical examination and CT or MRI imaging techniques. TTO combined with soft tissue realignment to ensure proper tracking is paramount to a successful graft healing. My preference is a longitudinal incision just off the midline laterally. In this way as the tibial tubercle is anterior medialized a skin incision is placed over the anterior muscle compartment and not over a bony prominence. If there is a wound breakdown, the bone is not exposed and the health of the wound is optimized. A lateral subvastus arthrotomy then allows visualization of the posterior femoral condyle, damaged patella, trochlea or all. An assessment of dysplasia of the trochlea can be performed at this time. The laxity of the medial soft tissue envelope can also be assessed. If the medial side of the knee is excessively lax to patellar stability, a medial arthrotomy is performed leaving a good cuff of tissue attached to the patellar portion of the extensor mechanism. The TTO can then be performed either leaving the distal hinge attached as per a classic Fulkerson-type osteotomy or making an oblique distal counter cut and elevating the extensor mechanism proximally ( Fig. 9.14 , a posterior lateral OCD lesion).

Fig. 9.14, Case example of a 39-year-old woman with a large osteochondritis dissecans lesion to the posterior lateral femoral condyle. This case demonstrates the use of tibial tubercle osteotomy (TTO) to expose a very posterior femoral condyle defect. (A) Tibial tubercle osteotomy is performed for a length of 6 to 7 cm in cancellous bone as an anterior medialization osteotomy. A lateral subvastus approach is performed, keeping the quadriceps entirely intact. The medial retinaculum is released to the mid-patellar pole at the level of the vastus medialis oblique insertion. Hoffa fat pad is released off the anterior tibial interval and anterior to the attachments of the menisci to the tibia. Exposure to the lateral femoral condyles is excellent. The tibial tubercle can be repositioned to a more central location to improve patellar tracking at the conclusion of the case. (B) View of lateral femoral condyle osteochondritis dissecans from the lateral aspect demonstrates just how posterior the exposure will allow you to go. It is a central lateral femoral condyle osteochondritis dissecans lesion, which is shallow at its margins and no deeper than 6 to 8 mm centrally. This defect will do well with isolated autologous chondrocyte implantation (ACI) without preliminary bone grafting or sandwich technique. (C) Close-up appearance of the defect after it is radically debrided and the tourniquet is let down to control bleeding. (D) Final appearance of the ACI graft after microsuturing of the periosteum and sealing with fibrin glue. (E) Anteroposterior and (F) lateral radiographs demonstrating well-healed TTO and well-preserved tibiofemoral joint space. (G) Two-year postoperative magnetic resonance imaging (MRI) with fat suppression demonstrating excellent cartilage repair fill to the defect. (H) Coronal MRI scan without fat suppression demonstrating complete fill. The patient remains asymptomatic.

Trochlea debridement and transplantation of the surfaces can then be easily performed. Trochlea articular cartilage is generally 3 to 5 mm thick. In order for postoperative rehabilitation to be without patellofemoral catching sensations, the debridement should involve the proximal and distal or leading and trailing margins of the defect to be slightly sloped towards the subchondral bone bed, and the medial and lateral margins to be vertical. When a defect is confined to an isolated medial or lateral trochlea facet, microsuturing a periosteal or collagen membrane flush to the articular surface is easy. However, when it crosses the midline sulcus, the order of stitching is important to restore the concavity of the trochlea ( Fig. 9.15 ), otherwise microsuturing without paying attention to this will result in a flat trochlea sulcus and abnormal forces to the membrane with possible early failure.

Fig. 9.15, Autologous chondrocyte implantation suturing technique to the trochlea, combined with tibial tubercle osteotomy. (A) When microsuturing a large defect of the trochlea across the midline sulcus, it is important to oversize the membrane in a medial to lateral direction. Suturing in a proximal to distal direction starting at the midline sulcus and working laterally and medially allows restoration of the concavity of the sulcus without undue tension on the membrane and an even depth throughout the entirety of the cartilage defect. (B) Close-up view of a trochlear defect in the left knee of a 32-year-old man who had undergone an extended tibial tubercle osteotomy. (C) The defect is clearly V shaped and will require a careful suturing technique to restore the articular topography. (D) Close-up view after debridement. (E) Microsuturing should start at the central sulcus proximal and distal (as shown) in an alternating medial and lateral pattern to restore the concavity to the trochlea. (F) Final appearance of the trochlea membranes sutured in place and sealed with fibrin glue. The superior opening sutures are left long. (G) Injection of autologous chondrocyte suspension underneath the opening, which was closed after the defect was filled.

Similarly, after tibial tubercle proximal ionization with subvastus laterally release patella debridement and transplantation of the surfaces can then be easily performed. The patellar cartilage is generally thicker than the trochlea, 5 to 7 mm thick, and therefore similar consideration for restoring the articular surface shape with the microsuturing technique is important ( Fig. 9.16 ). The medial and lateral margins of the debrided defect should be vertical to the subchondral bone and the proximal and distal margins should be slightly sloped to insure that tracking is without mechanical symptoms to the patient. However, when cartilage is thin, circumferential vertical margins are necessary. The microsuture technique in this situation is even more critical to restore the normal median ridge of the patella and insure that the membrane cover is not bottomed out on the subchondral bone so that there is always a cavity for the cell suspension to grow to the membrane surface.

Fig. 9.16, Microsuturing techniques for patella defects, combined with tibial tubercle osteotomy. (A) Isolated medial or lateral patella facet is a flat surface and easy to microsuture flush with the articular surface. (B) When the defect is large, as in this Fulkerson patella type IV chondral defect (pan-patellar), a good result depends on good debridement technique as well as microsuturing. If the cartilage is thick, bleeding and trailing edge should be slightly beveled to allow easy tracking in the proximal to distal direction and vertically on the medial and lateral margins to allow maximal membrane stability. (C) As in the trochlea, microsuturing should start at the apex or median ridge of the patella to “pitch the tent” and should then alternate medially and laterally in a proximal to distal fashion to restore the articular topography of the patella. This technique will maintain a uniform cavity deep to the membrane so that articular cartilage growth develops evenly to the limiting membrane. (D) Case example of a 42-year-old woman with chronic anterior knee pain bilaterally. Skyline x-ray films demonstrate well-preserved joint spaces. (E) Axial magnetic resonance imaging (MRI) scan with fat suppression demonstrates patellar tilt with fissuring and breakdown of the articular cartilage of the median ridge and medial facet of the patella. (F) Sagittal MRI scan demonstrates the same patellar damage but intact articular surfaces of the trochlea. (G) Extensile tibial tubercle exposure reveals an intact trochlea as noted by MRI. A fibrous cover over the biopsy site for autologous chondrocyte implantation is performed at the lateral intercondylar notch. (H) Metal probe demonstrates delamination and fissuring of the central and medial patellar surfaces. (I) Radical debridement of the damaged articular cartilage back to native subchondral bone and healthy cartilage margins. (J) Final appearance of microsuture collagen cover and restoration of articular topography of the patella.

At completion of the transplant, the tibial tubercle is fixated in a central and normalized position for the extensor mechanism. A vastus medialis oblique (VMO) advancement is then performed bringing the VMO under the medial patellar sleeve to advance and tension the VMO such that the patella may move 30% of its width medial and lateral in full extension without subluxation completely. The VMO muscle then helps to elevate the patella away from the trochlea decompressing it further as a soft tissue sleeve in addition to the TTO elevation. This is performed with no. 2 and Ethibond sutures with a horizontal mattress stitch (see Chapter 12 ; Fig. 12.25, Fig. 12.27 ). If there is trochlea dysplasia that is accounting for continued medial and lateral instability, the medial sleeve repair is taken down and a trochleoplasty is performed as the last step of stabilizing the patellar extensor mechanism and the soft tissue sleeve is readvanced and fixated as before. Congenital trochlear dysplasia is an uncommon factor contributing to patellofemoral maltracking. It is best assessed by preoperative CT scan demonstrating a flattened or convex superior trochlear capturing entry point. Treatment is by surgical trochleoplasty, combined with patellar realignment as necessary (see Chapter 12 ; Fig. 12.33, Fig. 12.34, Fig. 12.35 ). Results of trochleoplasty for trochlear dysplasia have been excellent.

ACI With OCD, Prior Bone Grafting, or Single-Stage Sandwich Technique ACI

In the case of bony deficiency, such as after an osteochondral fracture or osteochondritis dissecans, the depth of the bony lesion should be assessed preoperatively through radiography or CT scan. Osteochondritis dissecans defects, on average, are 6–8 mm deep including cartilage and bone. However, the margins are gradually sloped to the deepest portion. These often will do well without bone grafting, using chondrocyte implantation on its own ( Fig. 9.17 ). However, defects that are greater than 1–2 cm deep clearly need preliminary bone grafting and healing prior to cartilage resurfacing or a single-stage ACI sandwich technique. In addition, shallow defects with vertical walls, those that have cystic changes deep to the subchondral bone, and those with sclerotic bases from prior marrow stimulation techniques or osteochondral grafting should be considered for bone grafting or sandwich ACI. Autologous bone grafting may be performed either arthroscopically or by open technique ( Chapter 13 ). An interval of 6–9 months is required before second-stage articular resurfacing is performed. This allows the cancellous bone graft to harden as it is loaded with weight bearing after an initial period of 8 weeks of protected weight bearing. In this way a new subchondral bone plate is formed and minimal, if any, bleeding occurs at the time of preparation of the defect site prior to cell implantation.

Fig. 9.17, Illustrations and examples of the technique for autologous chondrocyte implantation with uncontained osteochondritis dissecans and deep defects requiring a sandwich technique. (A) The intercondylar aspect of the medial femoral condyle is a classic location for osteochondritis dissecans. After debridement, the defect becomes uncontained. The technique for making this a contained defect involves releasing the synovium from the posterior cruciate ligament and leaving it attached to its intercondylar attachment, as shown in the illustration. (B) Fibrin glue is placed on the medial aspect of the synovial attachment. The periosteum can then be microsutured to the surrounding articular cartilage and synovial membrane. (C) It is then sealed with Tisseel fibrin glue and the autologous cultured chondrocytes are injected. The opening is sutured over and sealed. (D) Clinical example of a left knee medial femoral condyle osteochondritis dissecans defect. The lesion is uncontained on the synovium of the posterior cruciate ligament (PCL). (E) After radical debridement, the synovial aspect of the PCL is brought up flush with the articular cartilage off the PCL. (F) Microsuturing and sealing the defect with Tisseel fibrin glue maintains the defect in a contained fashion.

A sandwich technique ACI was so named because it involves sandwiching autologous cultured chondrocytes between two layers of periosteum ( Fig. 9.18 ). When there is a deep defect requiring bone grafting, a radical debridement and undermining of the sclerotic or necrotic bone is performed with a high-speed bur with fluid irrigation. The base is then drilled to promote vascularization of the defect and autologous morselized cancellous bone is used to fill the defect to the level of the subchondral bone plate. A neural patty with thrombin and fibrin glue is applied to the bone graft while the tourniquet is let down. The autologous bone graft is saturated with blood and the surface kept dry. A layer of periosteum or collagen membrane is placed and fixated with fibrin glue or additional transosseous sutures with the cambium layer facing outward toward the joint. The surface is inspected to ensure that there is no marrow-derived bleeding through the membrane and into the defect. A second periosteal layer is then sutured flush to the articular cartilage as per usual ACI procedure. It is then sealed with fibrin glue and checked for water integrity. The saline is aspirated from the defect and autologous cultured chondrocytes are injected as per ACI, the opening sutured over and sealed with fibrin glue. Hence the autologous cultured chondrocytes are in a bioactive chamber with the underlying bone deficiency having been restored and the marrow-derived cells are separated from the autologous cultured chondrocytes, which are in a watertight chamber facing the cambium layer of periosteum on both sides.

Fig. 9.18, Diagrammatic representation and clinical example of a sandwich technique autologous chondrocyte implantation (ACI) for an osteochondral defect. (A) Diagrammatic representation of the final appearance of an osteochondral defect treated with ACI sandwich technique. As described in Chapter 13 , the osseous portion of the defect undergoes radical debridement of the necrotic or sclerotic bone, drilling deep to the osseous defect to promote revascularization, and autologous cancellous bone grafting to the level of the subchondral bone. At the level of the articular surface, a membrane or periosteum is used to contain the marrow-derived cellular response. A limiting membrane is sealed to the autologous bone graft with fibrin glue. If periosteum is used, the cambium layer faces the articular surface (pale green) . For the second membrane at the level of the articular surface, the cambium layer faces deep so that the two layers of cambium tissue sandwich the autologous cultured chondrocytes. The underlying marrow response is separated as a watertight separate chamber. (B) Clinical example of ACI sandwich technique in a middle-aged man with a varus knee and spontaneous osteonecrosis of the medial femoral condyle. The standing anteroposterior (AP) x-ray film demonstrates resorption and collapse of the medial femoral condyle with osteonecrosis (circled area) . The mechanical axis falls directly through the center of this lesion (single line). A 10-degree angular correction to the lateral tibial spine (intersecting lines) is required to unload the lesion by 2 degrees into mechanical valgus. (C) Lateral view of the proximal tibia bone deficiency demonstrates a 10-degree angular wedge of bone that was removed to allow performance of closing wedge osteotomy. (D) Autologous bone wedge from the closing wedge osteotomy will be morselized and used as cancellous bone graft to the medial femoral condyle avascular defect after it is radically debrided. (E) Probe demonstrates the medial femoral condyles avascular necrosis articular surface, which is ballotable and mobile. (F) Medial femoral condyles and defect after loose articular surface was easily removed. (G) Defect measured 1 cm deep after radical debridement of necrotic bony bed. (H) Appearance of medial femoral condyles after cancellous autologous bone grafting and packing to the level of the subchondral bony surface. (I) Periosteal membrane is sealed to the subchondral bone with Tisseel fibrin glue and tacked peripherally deep to the articular surface. A neural patty is applied with pressure to the periosteal cover while the tourniquet is let down to allow development of a watertight bed to the level that will undergo ACI. (J) Final appearance after the second periosteal cover, which is microsutured flush to the articular surface. Blue dot denotes the superficial fibrous periosteal layer surface of the membrane. The chamber between the two periosteal cambium layers is injected with autologous cultured chondrocytes and the margins are sealed with fibrin glue. (K) Standing AP radiograph 1 year after closing wedge valgus-producing osteotomy with ACI sandwich technique to the medial femoral condyle. The joint space is well maintained in the medial compartment. (L) Frontal view of the clinical appearance of left knee of the patient 1 year after closing wedge valgus osteotomy plus sandwich ACI. Note that the right knee is in slight varus and the left knee is in slight valgus. (M) Proton density magnetic resonance imaging (MRI) scan, coronal view, demonstrating excellent repair tissue cover of the medial femoral condyles. (N) Sagittal view with the same findings as shown in (M). (O) Sagittal delayed gadolinium-enhanced MRI scan of cartilage demonstrating proteoglycan content equal to adjacent nontransplanted cartilage, denoted by arrow . Nine years after surgery, the patient remains pain-free and is athletically active.

ACI Plus ACL

Cartilage repair in the face of cruciate insufficiency can jeopardize a newly regenerating cartilage graft. Staged or concomitant surgery should be performed with the goal of preventing shear forces and instability episodes from damaging a healing graft.

If there is any medial femoral condyle defect with ACL insufficiency, my preference is a single open incision from the superior medial pole of the patella to the inferior aspect of the tibial tubercle. A medial parapatellar arthrotomy is performed with the patella subluxed. An open technique ACL reconstruction is easily performed with only the femoral fixation having been completed with ACI to the medial femoral condyle ( Fig. 9.19 ). Once the autologous cultured chondrocytes are injected into the medial femoral condyle and sealed with fibrin glue, the knee is brought into extension, the tibia is translated posteriorly, and the tibial fixation completes the procedure with wound closure.

Fig. 9.19, Anterior cruciate ligament (ACL) reconstruction with autologous chondrocyte implantation (ACI) to the medial femoral condyle and patella in a 40-year-old man. (A) Open medial parapatellar arthrotomy, nerve hook demonstrating lax ACL torn from its femoral attachment. A medial femoral condyle defect with adjacent undermining is evident. (B) Radical debridement of the damaged articular cartilage to stable margins. When an open medial arthrotomy is performed, my preference is an open ACL reconstruction and open notchplasty. Tunnel placements are easy to acquire and perform. The same landmarks used arthroscopically are used for open technique. The femoral tunnel placement with the mini C-arm in a lateral position. (C and D) Final appearance of ACI grafts microsutured in place on the medial femoral condyle. (E) ACI appearance on the patella. Two years postoperatively, the patient has returned to pivoting sports and had no limitation.

For the lateral femoral condyle defect, two choices are available. If the defect is more anterior, I prefer the same approach as that used for a medial femoral condyle with hyperflexion and eversion of the patella and ACI to the lateral femoral condyle ( Fig. 9.20 ). The cells are injected and the patella is reduced with the knee extended and the tibia posteriorly translated. After femoral fixation for the ACL graft has been completed, the tibial fixation is performed and the wound closed.

Fig. 9.20, Anterior cruciate ligament (ACL) reconstruction with autologous chondrocyte implantation (ACI) to the lateral femoral condyle in an 18-year-old man. (A) Clinical appearance of the lateral femoral condyles defect as viewed through a medial parapatellar arthrotomy showing a lax ACL, femoral attachment injury. The other option in this case would be an arthroscopic ACL with lateral parapatellar arthrotomy after ACL reconstruction to perform the ACI. (B) Lateral femoral condyle defect after debridement. (C) ACL reconstruction with lateral femoral condyle ACI. (D) Coronal proton density magnetic resonance imaging (MRI) scan 1 year after surgery demonstrating excellent ACI repair tissue to the lateral femoral condyle. (E) Sagittal proton density MRI scan 1 year after surgery demonstrating excellent ACI repair tissue. (F) Confirmation arthroscopy 1 year after surgery. The patient is a high-level athlete and wishes to return to sports. I frequently perform MRI and second-look arthroscopy to confirm that a patient is ready to progress to high-level activity safely.

If the defect is more posterior on the lateral femoral condyle, I prefer an arthroscopically performed ACL followed by a lateral arthrotomy and open ACI to the lateral femoral condyle.

Anterior cruciate rehabilitation is modified to exclude closed-chain resisted strengthening exercises until 3 months after combined surgery to prevent excessive compressive load to the chondral repair site. Four to 6 months is required before these exercises may be started and leg presses and squats are avoided for 1 year after surgery. Rehabilitation follows that for ACI, which is the rate-limiting process in recovery.

ACI Plus Meniscal Allograft

When there is meniscal deficiency in combination with articular cartilage injury, I have found that it is much more critical on the lateral compartment of the knee than the medial to transplant the meniscus with the ACI. Medial injuries are frequently accompanied by varus malalignment. I presently have 25 years of results following valgus-producing tibial osteotomy with ACI to the medial femoral condyle in the presence of an absent meniscus with excellent clinical function and no evidence of joint space loss on standing x-ray examinations.

However, this is not always the case in the lateral compartment. Because of its meniscal dependency, the lateral compartment degenerates rapidly once the meniscus is lost even in the presence of a normal mechanical axial alignment. If there is valgus malalignment, the progression is much more rapid.

Meniscal transplantation can be performed arthroscopically using a slot technique, a posterior counterincision for posterior horn fixation followed by open arthrotomy, debridement of the chondral defects and microsuturing the periosteal membrane and ACI.

I have found it to be more straightforward to produce a slightly longer midline incision, develop a posterior deep fascial flap, and make the posterior capsular dissection for transcapsular meniscal fixation through a single open incision ( Chapter 14 ). The defect is debrided and the periosteal suturing performed. A slot technique is easily performed with passage of the meniscus posteriorly and posterior horn fixation. The body and anterior horn of the menisci are then easily repaired to the capsule by open technique. Transosseous fixation sutures can also be placed through the body and anterior horns of the meniscus to the tibial surface preventing postoperative extrusion of the meniscus. ACI is completed when the periosteum is glued, the cells are injected, the periosteum is closed and sealed, and the wound is closed. A single set-up without arthroscopic equipment makes the procedure quite easy. Excision of any posterior meniscal remnant is usually performed arthroscopically at the time of the cartilage biopsy so that it is not necessary at the time of the open meniscal transplant with ACI.

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