Use of Biologics for Degenerative Joint Disease of the Knee

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CHAPTER 6 Use of Biologics for Degenerative Joint Disease of the Knee

William J. Long

Key Points

Current cartilage-based techniques provide improved clinical outcomes when addressing full-thickness cartilage lesions of the knee.

Newer techniques promise further refinements, with less invasive techniques, though only short-term outcome studies exist.

There is no current technique that reproduces the native hyaline surface of the knee joint.

Introduction

Significant advances have been achieved at the two ends of the spectrum in addressing knee pathology: at one end with the arthroscopic management of knee injuries and at the other, with arthroplasty options for end-stage arthritis. The management of articular defects sits at the crossroads between these two settings. The goals of treatment for articular defects are to achieve a stable, durable, hyaline-like scaffold while correcting any instability or alignment disorder that may have contributed to the creation of the lesion. Treatment allows patients to return to their desired level of function, though patient education regarding the repaired knee and some degree of activity modification are almost always helpful.

Classification

Options available for addressing cartilage lesions can be classified as palliative, enhanced intrinsic repair, whole-tissue (allo- or auto-) transplantation, scaffold-based repair, cell-based repair, and combined techniques. The individual strategy selected should take into consideration the specific risks, benefits, and objectives of each technique in a patient-specific manner.

Approximately 60% of knees undergoing surgical arthroscopy for knee pain have articular cartilage changes.¹ Many of these injuries are only partial thickness and are of indeterminate significance in terms of their association with symptoms and their long-term progression to full-thickness chondral defects. Those with full-thickness lesions undergo approximately 400,000 cartilage procedures per year in the United States.² It is these cases that form the basis for the treatment options reviewed in this chapter.

Treatment Options

Palliative: Débridement

Irrigation and débridement is designed to address patient symptoms over the short term. Inflammatory mediators and loose fragments of cartilage are removed by the irrigation process. Débridement of the chondral defect removes any flaps of cartilage that may have been creating a mechanical block or irritation during range of motion. This technique is primarily palliative, and does not provide any basis for cartilage repair or regrowth.

Enhanced Intrinsic Repair: Microfracture

Due to the avascular nature of cartilage beyond the tidemark, there is limited to no regenerative potential. By breaking through this barrier, blood and associated healing and inflammatory mediators are exposed to the lesion. This reparative process, similar to the process of healing an injury in a nonarticular location, proceeds through clot formation, metaplasia, and remodeling. An area of scar or nonhyaline cartilage is produced, providing some cushioning, structural support, and symptomatic relief.

Current microfracture techniques are based on this endogenous potential for regeneration, first proposed by Purdie,³ and first described by Steadman and colleagues.⁴

Indications

Symptomatic full-thickness chondral defects of the knee can be treated with microfracture techniques.

Technique

Appropriate visualization of the lesion must be achieved. Meticulous débridement of any thin overlying fibrous tissue and calcified cartilage exposes a healthy defect bed. A vertical stable shouldered border must be created to shield the healing area. A microfracture awl is then inserted and holes are made beginning in the periphery and moving centrally. Spacing of approximately 3 mm with lesions to a depth of 3 mm should be achieved. Arthroscopic inflow is occluded and holes can be visualized for bony bleeding, indicating an appropriate depth of penetration.

Postoperative Management

Classical training dictates a strict protocol of touch-down weight bearing and continuous passive motion (CPM) for 6 weeks.⁵ Animal models demonstrate an extended healing period up to 12 weeks, thus suggesting a potential benefit to a longer period of restricted load bearing. In contrast, a clinical study by Marder et al. compared this protocol to one of unrestricted weight bearing and no CPM for femoral chondral lesions less than 2 cm². At a mean 4.2-year follow-up (2–9 years) there was no difference in Lysholm and Tegner scores between groups.⁶

Outcomes

At early,⁷ midterm,⁸ and long-term⁹ follow-up, good results have been reported in clinical function and pain relief with microfracture. Good fill grades, low body mass index, younger age, lack of associated meniscal and ligamentous injuries, and shorter duration of preoperative symptoms are predictive of improved outcomes.

Traditional Cell-Based Technique: Autologous Chondrocyte Implantation

Indications

Lesions from 2 to 10 cm² in any area in the knee can be treated with this technique.

Technique

Originally described by Brittberg et al.¹⁰ in 1994, autologous chondrocyte implantation (ACI) is a two-stage technique that requires harvesting, culturing, and implantation of autologous chondrocytes. In the initial stage, surgical arthroscopy is used to assess whether or not the patient is a candidate for ACI; to address any associated meniscal pathology; to template the size, location, and dimensions of the defect; to locate any other cartilage lesions; and to obtain cartilage for culture. Typically the lateral edge of the notch, at the site of an anterior cruciate ligament notchplasty, is a good location for cartilage harvesting. A small curette or gouge can be used to harvest two to three small samples of cartilage, each about 3–5 mm in size. Samples are sent to a central lab. There these autologous cells are cultured to expand the cell count by up to 50 times. Chondrocytes are stored until appropriate time for implantation.

Using information gathered at the time of arthroscopy, an appropriately sized and positioned mini-arthrotomy is planned. The skin incision must be made while considering the need for a well-positioned arthrotomy, the periosteal patch harvest, and any future surgical management. Thus a midline incision is most often used. Following exposure of the lesion, it is débrided to stable borders and down to, but not through, the subchondral plate. The cross-sectional dimensions are measured and traced onto a sterile piece of paper. This is then used to harvest a periosteal flap approximately 2 mm larger than the defect. The outer layer should be marked so that the deep or cambium layer is placed facing the defect.

The periosteal patch is sutured into place with a 6-0 Vicryl stitch. An initial polar stitch in all four quadrants is helpful to appropriately position the graft, followed by interrupted simple sutures at 2- to 3-mm intervals. A small superior 5-mm opening is left to allow insertion of the cultured chondrocytes. The edges of the remainder of the patch are reinforced with fibrin glue, and the watertight nature is tested with saline. Appropriate reinforcements are made. The cultured chondrocytes are then inserted. Final sutures are tied and fibrin glue is applied. The knee is taken through a range of motion to ensure that the patch is stable and watertight.

Postoperative Management

Restricted weight bearing combined with early range of motion and CPM are begun immediately following surgery. Gradual progression of weight bearing and strengthening activities should be individually dictated by the size and location of the lesion. Impact activities are typically restricted for 6–9 months following ACI.

Outcomes

Long-term outcomes demonstrate durable results with ACI at 10–20 years postprocedure.¹¹ At a mean 12.8-year follow-up, 92% of patients were satisfied with results and would have the procedure again. Vasiliadis et al. examined the long-term magnetic resonance imaging appearance of lesions at 9–18 years. Though some degeneration was noted, the quality of the repair tissue was similar to that of surrounding normal cartilage.¹² In a double-blind trial, Knutsen et al. did not note any difference between short-term outcomes with ACI and microfracture, with both techniques demonstrating good results.¹³

Emerging and Developing Technologies

Despite clinical success with current conventional techniques, limitations exist. Inferior biomechanical properties of the reparative tissue,¹⁴ and progressive degeneration of the mixed reparative tissue created,¹⁵ limit success with a microfracture technique. Osteochondral autografts are limited by the availability of transplantable tissue. ACI is costly and time consuming and requires two surgeries, harvesting of a periosteal flap and an open arthrotomy. New technologies are currently in varied stages of development, and will seek to expand the options available for addressing cartilage lesions. These techniques are broadly categorized as cell based, and non–cell based. It is important to note that the Food and Drug Administration (FDA) has yet to approve any of these new techniques. Carticel (Genzyme, Cambridge, MA), approved by the FDA in 1995 for ACI, remains the only approved implant system in this field. As with any novel technology, long-term data do not exist to support their use. A few selected devices and techniques are reviewed.