BERLIN, Germany—Patients with early stages of knee osteoarthritis (OA) might soon be able to repair their knees rather than replace them. Christian Ossendorf, MD, with the department of traumatology and orthopaedic surgery at the University of Freiburg, in Germany, and colleagues report in Arthritis Research & Therapy promising 2-year clinical results with the BioSeed®-C autologous chondrocyte implantation graft.¹ The polymer-based graft also has the advantage that it can be positioned via arthroscopy in some patients.

"In the present study, we showed the benefit and reliability of the use of the autologous gel-polymer-based cartilage tissue engineering graft BioSeed-C for the treatment of full-thickness cartilage defects of the knee. The evaluation of the clinical outcome two years after implantation demonstrated that BioSeed-C is well suited for the treatment of patients with posttraumatic and mild degenerative defects as well as for the treatment of focal osteoarthritic defects," the investigators write.

The graft was tested in patients with cartilage defects resulting from either knee OA or injury. Of the 79 patients initially treated, Dr. Ossendorf reports 2-year follow-up data for 40 patients: 13 with knee OA and 27 with posttraumatic and/or mild degenerative defects and no signs of OA. Despite their relative young age (mean 36 years, range 17-to-64 years), these patients had been through a large number of prior procedures. Additional procedures performed when implanting the grafts included 10 anterior cruciate ligament reconstructions, 10 high tibial osteotomies, two drilling/microfractures, one patella realignment, and one medial capsular shift.

Bioengineered scaffold supports and guides chondrocyte redifferentiation

The engineered grafts are meant to "ensure the even distribution of a high number of vital chondrocytes, mediate initial biomechanical activity, promote chondrocyte differentiation and formation of cartilage matrix, inhibit chondrocyte proliferation, and allow the easy handling of the graft by the surgeon," the authors write. The autologous chondrocytes are placed in gel-like matrices in a polymer scaffold that is initially mechanically stable but is bioresorbable. The fibrin and polymer-based scaffolds initiate the redifferentiation of the dedifferentiated cultured chondrocytes, which are immobilized in and protected by a fibrin-polymer matrix and require no additional cover materials.

The autologous chondrocytes for the grafts were isolated from 250 mg of healthy cartilage harvested arthroscopically from a less weight-bearing area of the knee and expanded in vitro. Twenty million cells were rearranged 3-dimensionally in the scaffold, fitted to the size of the defect, and implanted (arthrotomically or arthroscopically) into the site, in which defective cartilage had been debrided down to the subchondral bone.

Clinical results were evaluated with the Modified Cincinnati Knee score, the Lysholm score, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the International Knee Documentation Committee evaluation form at baseline, 3, 6, 12, and 24 months after transplantation of the graft. MRI was used to examine repair and resurfacing of the cartilage defects at 6 and 12 months after transplantation, and 14 of 79 patients had second-look arthroscopy for investigative and diagnostic purposes.

Chondrocyte graft might be boon to young, active patients with knee OA or defects

At the 2-year follow-up, Dr. Ossendorf et al reported significant improvement of all of the outcome measures and histological staining of biopsies showed "good integration of the graft and formation of a cartilaginous repair tissue." The OA patients had significant improvement in the KOOS subclasses for pain, other symptoms, and knee-related quality of life. "The results suggest that implanting BioSeed-C is an effective treatment option for the regeneration of posttraumatic and/or osteoarthritic defects of the knee," they write.

The investigators note that autologous chondrocyte is not conventionally considered to be appropriate for OA patients, and that it would be a desirable option for young patients with early-stage OA or with deformities that predispose to OA, perhaps as the result of knee trauma. "These patients lack decent treatment options and are too young for total joint replacement. This is particularly true for those having an active lifestyle that includes sports or demanding recreational activities," Dr. Ossendorf writes. He suggests that as a first step in such patients, this type of chondrocyte graft might postpone total joint replacement for a decade.


Figure: Arthroscopic and magnetic resonance imaging evaluation of cartilage defects treated with autologous chondrocyte grafts (BioSeed^-C).
(A) Intra-operative situation of a cartilage defect at the femoral condyle covered with transosseously fixed BioSeed^-C (20 x 30 mm). Healthy cartilage
rim is partly intact. (B) 9 months postoperatively, second-look arthroscopy showed the formation of a cartilage repair tissue (asterisk). (C) MRI at 6 months and at 12 months. (D) shows transosseous drilling holes (white asterisks) due to fixation of the graft. The repair tissue covers the defect (white triangles) and gives a slightly altered MRI signal. (Source: Ada[ted from Ossendorf C, et al.¹ Used with permission.)


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Reference

1. Ossendorf C, Kaps C, Kreuz PC, et al. Treatment of posttraumatic and focal osteoarthritic cartilage defects of the knee with autologous polymer-based three-dimensional chondrocyte grafts: Two year clinical results. Arthritis Res Ther. 2007;9:R41. doi:10.1186/ar2180.