**7.1 Evolution of technique**

Arthroscopic surgeons are regularly faced with the challenges of providing a satisfactory end result for the treatment of chondral lesions. Prior to the development of the current method, the first author was treating chondral lesions with standard subchondral drilling followed by postoperative intraarticular injections of hyaluronic acid (HA). This being a variant of marrow stimulation technique, produces fibrocartilage which is not as resilient as the original hyaline cartilage. The newly regenerated fibrocartilage gradually deteriorated with time. Since Year 2005, the first author has been dissatisfied with the inconsistent end results following this method of cartilage repair as shown in Fig 6.

Fig. 6. Intraoperative view after subchondral drilling of the lateral patella facet - right knee (A). Second-look at 18 months (B) showing partial coverage of the defect with fibrocartilage.

At the same time, veterinary surgeons have shown that injections of bone marrow aspirate into race horse's flexor tendon injuries resulted in satisfactory healing (Pacini et al, 2007; Taylor et al, 2007; Thomas et al, 2008 & Violini et al, 2009). This gave rise to the idea of utilizing stem cells in the knee joint to initiate articular cartilage repair after subchondral drilling.

A literature search suggests that the mesenchymal stem cell (MSC) is a better alternative to the chondrocyte as it is a less differentiated cell and is capable of differentiating into both bone and articular cartilage. As most chondral lesions involve both these components, cells that are capable of forming both bone and cartilage should theoretically

Articular Cartilage Regeneration with Stem Cells 139

In the animal model, we wished to find out whether postoperative intraarticular injections of autologous marrow aspirate (MA) and HA after subchondral drilling could result in a

A 4 mm full thickness articular cartilage defect was created in the stifle joint, followed by subchondral drilling as shown in Fig 8. The animals were divided into three groups: group A (control), no injections; group B (HA), weekly injection of 1 mL of sodium hyaluronate for 3 weeks; and group C (HA + MA), similar to group B but with 2 mL of autologous MA in addition to HA. MA was obtained by bone marrow aspiration, centrifuged, and divided into aliquots for cryopreservation. 15 animals were equally divided between the groups and sacrificed 24 weeks after surgery, when the joint was harvested, examined macroscopically

Fig. 8. (A&B) A 4mm full thickness articular cartilage defect was created in the stifle joint,

The chondral defects were covered with repair tissue in all groups, without evidence of synovitis or synovial thickening (Fig 9). In group A the defects were covered with semitransparent tissue having recognizable margins but with an irregular surface. A similar appearance was seen in group B goats. In group C the defect coverage was almost complete, and the color of the repair tissue was indistinct from surrounding cartilage. The surfaces

Under H&E staining, scar tissue was present in group A, which was characterized by a disordered arrangement of fibroblasts in an edematous stroma (Fig 9). The interface of scar tissue with subchondral bone was marked by the presence of dilated capillaries and venules. In group B scar tissue was less pronounced, and islands of hyaline-like cartilage were seen at the interface with subchondral bone and also adjacent to normal cartilage at the defect margins. Edema was also less marked than in the control group. In group C there was chondrogenesis with evidence of hyaline cartilage formation. The hyaline cartilage also showed features of maturation as evidenced by a linear arrangement of chondrocytes extending from the subchondral bone toward the surface. No edema was seen in this group. With Safranin-O staining, proteoglycans were notably absent from the repair tissue in group A. In group B proteoglycans were seen only at the base and sides of the defect in the same distribution as the hyaline-like cartilage. In group C there was marked proteoglycan accumulation in the deeper layers, excluding the perichondrium, which

were smooth and appeared level with adjacent normal cartilage.

better cartilage repair.

and histologically (Fig 9).

followed by subchondral drilling.

**7.2.1 Macroscopic findings** 

**7.2.2 Histologic findings** 

normally does not contain proteoglycans.

be able to regenerate into tissue that will integrate better with the surrounding native structures. This may minimize of delamination which is occasionally seen by the autologous chondrocyte implantation (ACI) technique. Fig 7 shows the potential differentiation process of MSC.

Fig. 7. Potential differentiation process of MSC.

Open surgery does not appeal to arthroscopic surgeons. The ideal method of articular cartilage repair would be a single arthroscopic procedure followed by an adjunct cell therapy which could be performed in the out-patient setting. Obviously the desired end result should be the regeneration of the original hyaline cartilage with clinical improvement. The arthroscopic surgeon's wish list for chondrogenesis is listed below:

