Introduction

Historical Perspective

Autologous chondrocyte transplantation is known as autologous chondrocyte implantation (ACI) in North America. After several visits to Sweden in the early 1990s, I adapted the technique described by Peterson and coworkers¹ (Figure 7–1). After institutional review board approval was given in 1994, the technique of ACI has been used to manage large acute and chronic focal articular cartilage injuries in the knee since March 1995. As of 2010, more than 600 treatments have been performed at our institution. More than 15,000 patients have been treated with ACI in North America and another 20,000 have been treated worldwide, for a total of 35,000 patients.

Figure 7–1 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.

Use of autologous chondrocytes for patient care in the United States has been carefully regulated by the U.S. Food and Drug Administration (FDA, Biologics Division) and has required both Good Laboratory Practices (GLP standards) and Good Manufacturing Practices (GMP standards) since its introduction in the United States. This practice has been cost prohibitive to private and academic institutions with regard to patient care and therefore has been performed by industry (Genzyme Biosurgery, Cambridge, MA). As of August 22, 1997, the FDA formally approved ACI (FDA Biologics License 1233) for the management of focal chondral defects of femoral articular surfaces. This approval was based on the early data of 159 patients evaluated in Sweden as of 1997. Because early results were not favorable for management of the patella or tibia or for cases involving early bipolar or arthritic lesions, these defects have been considered “off label.” However, prior to the FDA approval, I had gained considerable experience in the treatment of these off-label uses based upon experience with patients who had been referred for management of these troublesome lesions.

In my experience, the patient who is highly motivated, is realistic about 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 Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) proved to be high statistical predictors of a good physical outcome in a study conducted at our institution and presented at the International Cartilage Repair Society in Toronto Canada 2001.² Patients younger than 18 years also have an excellent chance of returning to full activities.³

This chapter discusses the role of ACI for the treatment of full-thickness cartilage injuries of the knee. Since the initial publication on this topic,¹ there has been a renewed interest in the treatment and research of this clinical problem. The earlier published study indicated good and excellent results in 14 of 16 patients treated on the weight-bearing femoral condyles. Only 2 of 7 patients with patellar lesions who were treated had similar results.

Arthroscopic assessment and cartilage biopsy for cell culturing

Arthroscopic assessment of the joint and possible biopsy for articular cartilage culturing require careful and systematic evaluation of the articular surfaces with an arthroscopic probe to demonstrate and determine the extent of grade III and IV chondromalacia 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 the chondromalacia is no greater than grade II (superficial fissuring) ideally, otherwise it may also be considered for repair if the radiographic joint space is intact and the defect rim is healthy (Figure 7–2). 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 be assessed. This will determine whether healthy cartilage will be available for periosteum or colagen membrane suturing or whether an uncontained chondral injury will require suturing through synovium or small drill holes through the bone. The posterior extent of the lesion is critical because it must be accessed at the time of open arthrotomy for periosteal suturing.

Figure 7–2 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 also is a candidate for ACI.

If a lesion is considered appropriate for treatment, then a biopsy site for cartilage procurement must be selected (Figure 7–3). In Europe, the site most commonly chosen for biopsy is the superior medial edge of the trochlea, adjacent to the medial patella (odd) facet (Figure 7–4). The biopsy site will not produce a reciprocal symptomatic injury because there will be no opposing articular surface to make its contact. The patellofemoral joint must be assessed carefully. If a patellar facet is overhanging on the medial side, often the superior lateral facet may be harvested. My preferred location is the superior and the lateral intercondylar notch because it is convenient and is known to not create problems when removed, as in anterior cruciate ligament (ACL) reconstruction (Figure 7–5). Finally, the superior transverse trochlea margin adjacent to the supracondylar synovium, which may be biopsied through a separate superior portal, or the distal lateral trochlea at the sulcus terminalis as per harvesting an osteochondral autograft transfer system graft. At the time of open implantation, the synovium may be advanced over the biopsy site via sutures through the articular cartilage.

Figure 7–3 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 taken from the margins of the trochlea should be taken 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, Another location that can be used is the superior portion of the trochlea on the medial corner when all other sites are not appropriate.

Figure 7–4 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. Frequently the distal lateral trochlea proximal to the sulcus terminalis can be used.

Figure 7–5 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 on the tibial spines or the weight-bearing surfaces is seen.

Approximately 200 to 300 mg of articular cartilage is required for enzymatic digestion for cell culturing. This is approximately a cartilage surface of 5 mm wide by 1 cm long. This piece will contain approximately 200,000 to 300,000 cells, which may be enzymatically digested and grown to approximately 12 million cells per 0.4 ml 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 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 can 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 to 5 weeks later, a suitable number and volume of cells will be grown to accommodate the required defect size. At this time, second-stage open implantation may occur.

Surgical correction of background factors predisposing to chondral injury

Several factors predisposing to chondral injury must be assessed so that they can be 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 reimplantation.

Long-leg alignment is evaluated in all patients (see Chapter 3) with double leg stance long alignment digital radiographs that include the 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 tomographic (CT) scan can be performed with the knee in extension, first with the quadriceps in the relaxed and then in the contracted position to assess patellofemoral subluxation (see Chapter 10). 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 or an examination under anesthesia may be necessary.

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

Although arthroscopy is helpful in assessing the depth and character of an osteochondral defect, CT scan generally is more useful in determining the presence of subchondral bony cysts 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 are discussed after 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 used. This is usually accomplished through a midline skin incision or a longitudinal parapatellar incision. Adequate exposure is crucial to good suturing of periosteum, and several retractors are often required in order to obtain this goal. Posterior lesions on the femur will often require hyperflexion of the knee and occasional takedown of the meniscus in subperiosteal fashion with intermeniscal ligament takedown and coronary ligament release off the tibia as the meniscus is peeled back with the entire sleeve of tissue (Figure 7–6). A repair of these at the end is then 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.

Figures 7–6 Deep dissection of a medial or lateral arthrotomy to obtain exposure to the posterior medial femoral condyle or tibial plateau, or a lateral femoral condyles 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, as is the coronary meniscal attachment on the tibia 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, As the medial sleeve is taken down in a posterior direction off the tibia to expose the posterior tibial plateau but is still too tight, then a bone block attachment to the femoral condyles 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 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 frequently is difficult if the tibial tubercle is positioned laterally on the tibia. In this case, a tibial tubercle osteotomy (TTO) and elevation are helpful for exposing the lesion and realigning the extensor mechanism centrally (see section on ACI plus Tibial Tubercle Osteotomy for Posterior Exposure/with Patella/Trochlea ACI). This method 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 due to inadequate debridement with poor integration to adjacent cartilage, leading to progression of disease in the adjacent nondebrided fissured cartilage or delamination of the repair tissue from the damaged native tissue. Oval or curvilinear excisions are made using a no. 15 blade to incise 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 so 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 microholes through bone drills (Figure 7–7). Once a healthy defect bed is prepared, its length and width are measured. If the bed is irregularly shaped, then a template can be made with sterile tracing paper (sterile glove packaging paper works well). A sterile marker can be used to make a template of the defect, which can be cut out to fit the defect perfectly. This template then 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 pen directly onto the periosteum if it is an uncomplicated shape and then cut directly (Figure 7–8).

Figure 7–7 Transosseous drill hole fixation for uncontained cartilage defects. A large uncontained lateral trochlea 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.

Figure 7–8 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 off the bone, maintaining the deep cambium layer orientation. The superficial fibrous layer is marked with a sterile marking pen to ensure this orientation.

Any subchondral thickening, sclerosis, or intralesional osteophyte formation at the base of the chondral defect as a result of a prior marrow stimulation technique (drilling, abrasion, microfracture) 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 native subchondral bone (Figure 7–9). This will provide a cavity for the cell suspension, which is injected underneath the membrane cover and will lessen the stiffness of the subchondral bone so that newly forming cartilage repair tissue will integrate and 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. Bleeding, if it occurs, usually is scant and easily managed with a neural patty soaked with thrombin and epinephrine or with a drop of fibrin glue. Occasionally a fine-tip electrocautery is used.

Figure 7–9 Takedown of sclerotic bone/intralesional osteophytes. A, Intralesional osteophytes may form after marrow stimulation techniques (abrasion, drilling, microfracture) as well as from idiopathic osteoarthritis. B, A 5-mm high-speed bur is used to gently under irrigation may be been used to 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 down is also found in patients having early osteoarthritis with chronic articular chondral defects. In these cases, the surrounding cartilage is often thinned out, and the periphery of the defect is marginally uncontained. A contained defect can be made using a high-speed bur to deepen the area of bony exposure to a level of more normal-appearing subchondral bone and using transosseous drill holes around the periphery to anchor the membrane and provide a cavity for the cartilaginous tissue repair. Frequently this has been my method of repair for patients in the salvage category of treatment.

The easiest and most suitable location for periosteum procurement is the proximal medial tibia, distal to the pes anserinus insertion on the subcutaneous border. This site has subcutaneous fat, a very thin fascial layer, and easy access to the periosteum. Once defect size has been assessed and a template made, a second incision is made approximately a finger’s breadth distal to the pes anserinus insertion, in the center of the medial subcutaneus border of the tibia. Subcutaneous fat is incised initially, and then scissor dissection will reveal the shiny white proximal tibial periosteum. A wet sponge can be sued to sweep away loose areolar tissue. Electric cautery should not be used around periosteum because it will necrose the periosteum with the very sensitive cambium layer of cells on its deep surface.

The template is placed on the periosteum; alternatively it is marked with a ruler and a sterile marking pen. A sharp no. 15 blade is used to incise sharply, oversizing the periosteum 1 mm in all directions down to bone. A small sharp periosteal elevator is useful for very gently advancing the periosteum from its bony bed and preventing it from under-rolling so that it does not rip. Nontoothed forceps will aid in pulling 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 with its removal. The outside of the periosteum should be marked as the superficial surface so that it is not inadvertently placed on upside down.

At this time the defect site is inspected, 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 does not appear to be violated. Any bleeding of the bony bed can usually be stopped using a combination of thrombin and epinephrine soaked in a neural patty, which is applied to the defect and gently pressed for several minutes. If some bleeding continues after the neural patty is removed, a small drop of fibrin glue will usually suffice to dry the defect.

The goals of periosteum or collagen membrane fixation are threefold: (1) to provide a watertight membrane that acts as a mechanical seal, (2) to act as a semipermeable membrane for intraarticular synovial nutrition to chondrocytes, and (3) to maintain a viable periosteal cambium layer of cells so that interactive growth factors between chondrocytes and periosteum can enhance chondrocyte growth. These factors include transforming growth factor-β, insulin-like growth factor, interleukin-2 (IL-2), and IL-6. They have been found to enhance chondrocyte colony formation when they are 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 6.0 Vicryl suture on a P-1 cutting needle, which has been immersed in sterile mineral oil or glycerin. An 8-inch length usually is adequate; the remainder of the suture is cut off and discarded. Suturing is done in an interrupted and alternating fashion. Sutures are placed through the periosteum and then the articular surface. The knots are tied on the side of the periosteum so that they remain below the level of the adjacent cartilage. In this way, they will not unravel with motion and evert the periosteal edge; rather, they act as a washer seal on the edge of the vertical articular cartilage defect (Figure 7–10). Hence, a watertight seal can be obtained by suture technique alone in most cases. When alternately suturing corners, the analogy of tightening up a drum skin alternately is followed. 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 to check edge integrity and then chondrocytes. Interval sutures of approximately 3 to 6 mm are made and protrude through the articular surface by at least 3mm.

Figure 7–10 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 so as 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, Four 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 length 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 more likely will undergo full, even cartilage fill for the length of the defect.

Periosteum watertight integrity testing is assessed using a plastic 18-gauge 2-inch angiocath with a tuberculin syringe filled with saline. This step is usually avoided when a collagen membrane cover has been used because it tends to displace the cell suspension and prevents it from being absorbed to the collagen membrane, which is the desired effect. The angiocath is placed deep to the periosteum into the defect, and the defect is gently filled 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 achieve water integrity. The saline then is aspirated out of the defect. If water integrity cannot be obtained by suture technique alone, then a fibrin sealant is also used.

For autologous fibrin sealant, the patient must donate 1 unit of whole blood preoperatively. The whole blood is spun off for a pack of red blood cells as well as a supernatant, which is concentrated to produce cryoprecipitate by a double-spin freeze–thaw technique. This process takes 14 days of preparation prior to surgery. Following the double-spin freeze–thaw technique, a concentration of approximately 80 to 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; the other barrel contains a 50/50 admixture of 10% calcium chloride and a superconcentrated bovine thrombin. Fibrinogen is cleaved into active fibrin, which is deposited along the margins of the defect, sealing them. Commercially available Tisseel (Baxter Biosurgery, Deerfield, IL) is made from pooled human serum and is available in Europe and the United States.

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

The procedure is now complete. Drains generally are not used within the joint so as not to damage the periosteal patch or suck out the cells from the defect but should be used without suction if needed. The wound is closed in layers, and a soft dressing is applied to the knee.

Advanced techniques for surgical transplantation of autologous chondrocytes

Exposures

Posterior Femoral Lesions and Tibial Plateaus

When attempting to approach a femoral condyle lesion that is very posterior or a tibial plateau lesion, and 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 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 midcoronal plane. This usually is enough to get to a posterior medial femoral condyle. Two options are available to get to the midportion of the medial tibial plateau or the posterior portion. The deep medial collateral ligament 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. Transosseous sutures with no. 2 Ethibond can be used to reattach the sleeve of tissue back to its native position at the time of closure. This process 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 can pass directly through the bone in one easy step. The anterior horn of the medial meniscus is reattached through transosseous sutures back to its native origin. 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 condyle, 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 (Figure 7–11).

Figure 7–11 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 exam intact. She has tricompartmental crepitus and joint effusions on clinical examination. 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 peeled subperiosteally with the sleeve, which will often include some of the attachment of the iliotibial band insertion at Gerdy’s tubercle. The patella is subluxed into the medial parapatellar gutter, and the knee is hyperflexed and internally rotated. This will usually deliver the lateral tibial plateau quite well and will expose the posterior lateral femoral condyles. This step may not be possible if the knee is stiff and the tibial tubercle insertion is located very laterally. In this situation, TTO 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 the procedure for tibial plateau injury is completed (Figure 7–12).

Figure 7–12 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 coronal magnetic resonance imaging (MRI) scan (A) and a sagittal MRI scan (B) 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. This is 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. Microsuturing of the ACI graft and sealing of its margins with fibrin glue. A single suture is left long laterally to allow injection of the autologous chondrocyte suspension and then is easily closed and sealed over. Final radiographic appearance after femoral varus-producing osteotomy with lateral tibial plateau ACI graft.

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, then a corrective osteotomy is paramount to the success of ACI. This can be done in either a staged or a concomitant fashion. My preference is to perform the procedure all at once. A single longitudinal incision will achieve the exposure for both procedures quite easily. However, it is imperative that if the procedure 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 can 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 a varus knee in combination with a trochlea or patellar injury. If the condition 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 (Figure 7–13). A medial parapatellar arthrotomy is performed, the defect is débrided, and a template is made. The template is applied to the periosteum, which has been exposed distal to the pes anserinus tendons, and the periosteum is harvested. Takedown of the pes tendons and superficial medial collateral ligament is performed in preparation for tibial valgus-producing osteotomy (see Chapter 8). The osteotomy is performed and fixated. The tourniquet is let down, and any bleeders in the soft tissue envelope or the subchondral bone plate in the area to be transplanted are resolved. Careful suturing and transplantation to the medial femoral condyle is performed.

Figure 7–13 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 trochlea 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 to maintain the convex shape of the patella 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 treated, which now had become equally painful as the right knee originally had been. The right knee has served him without pain and allowed him to return back to coaching and running on the sidelines until the demise of his left knee. The left knee was treated with identical lesions, with excellent clinical outcome.

If arthroscopy revealed maltracking of the patella with or without a chondral defect, TTO is performed with a medial subvastus and lateral subvastus arthrotomy elevating the extensor mechanism proximally. The defects are debrided, the periosteum is harvested, and the tibial valgus osteotomy is performed and fixated (see Chapter 8, combined osteotomies). The periosteal covers are 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 by physical examination and CT or MRI. TTO combined with soft tissue realignment to ensure proper tracking is paramount to 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. In the event of wound breakdown, the bone is not exposed and the health of the wound is optimized. A lateral subvastus arthrotomy allows visualization of the posterior femoral condyle, damaged patella, trochlea, or all of these. Assessment of dysplasia of the trochlea can be performed at this time. The laxity of the medial soft tissue envelope also can be assessed. If the medial side of the knee is excessively lax to patellar stability, then a medial arthrotomy is performed, leaving a good cuff of tissue attached to the patellar portion of the extensor mechanism. TTO can then be performed either leaving the distal hinge attached per a classic Fulkerson-type osteotomy or making an oblique distal countercut and elevating the extensor mechanism proximally (Figure 7–14), a posterior lateral osteochondritis dissecans lesion.

Figure 7–14 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 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 midpatellar 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 condyles osteochondritis dissecans from the lateral aspect demonstrates just held posterior the exposure will allow one to go. This is a central lateral femoral condyle osteochondritis dissecans lesion. It 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. Anteroposterior (E) and lateral (F) radiographs demonstrating well-healed tibial tubercle osteotomy 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 proceed without patellofemoral catching sensations, the debridement should shape the proximal and distal (or leading and trailing) margins of the defect so that they slope slightly toward the subchondral bone bed, and the medial and lateral margins should be vertical. When a defect is confined to an isolated medial or lateral trochlea facet, then microsuturing a periosteal or collagen membrane flush to the articular surface is easy. However, when the defect crosses the midline sulcus, the order of stitching is important to restore concavity of the trochlea (Figure 7–15). Microsuturing without attention to this step will result in a flat trochlea sulcus and abnormal forces to the membrane with possible early failure.

Figure 7–15 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 as shown in Figure 7–14. C, The defect is clearly V shaped and will require a careful suturing technique to the store at 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 be easily performed. The patellar cartilage is generally thicker than the trochlea (5-mm thick), so consideration for restoring the articular surface shape with the microsuturing technique is important (Figure 7–16). 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 ensure that tracking occurs without mechanical symptoms to the patient. However, circumferential vertical margins are necessary when cartilage is a thin. In this situation, the microsuture technique is even more critical to restoring the normal median ridge of the patella and ensuring that the membrane cover is not bottomed out on the subchondral bone. With this technique, there is always a cavity for the cell suspension to grow to the membrane surface.

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