The Evaluation of Cartilage Regeneration Efficacy of Three-Dimensionally Biofabricated Human-Derived Biomaterials on Knee Osteoarthritis: A Single-Arm, Open Label Study in Egypt

Abstract

Full thickness cartilage defects in cases of knee osteoarthritis are challenging in nature and are difficult to treat. The implantation of three-dimensional (3D) biofabricated grafts into the defect site can be a promising biological one-stage solution for such lesions that can avoid different disadvantages of the alternative surgical treatment options. In this study, the short-term clinical outcome of a novel surgical technique that uses a 3D bioprinted micronized adipose tissue (MAT) graft for knee cartilage defects is assessed and the degree of incorporation of such graft types is evaluated via arthroscopic and radiological analyses. Ten patients received 3D bioprinted grafts consisting of MAT with an allogenic hyaline cartilage matrix on a mold of polycaprolactone, with or without adjunct high tibial osteotomy, and they were monitored until 12 months postoperatively. Clinical outcomes were examined with patient-reported scoring instruments that consisted of the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score and the Knee Injury and Osteoarthritis Outcome Score (KOOS). The graft incorporation was assessed using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. At 12 months follow-up, cartilage tissue biopsy samples were taken from patients and underwent histopathological examination. In the results, at final follow-up, the WOMAC and KOOS scores were 22.39 ± 7.7 and 79.16 ± 5.49, respectively. All scores were significantly increased at final follow-up (p < 0.0001). MOCART scores were also improved to a mean of 82.85 ± 11.49, 12 months after operation, and we observed a complete incorporation of the grafts with the surrounding cartilage. Together, this study suggests a novel regeneration technique for the treatment of knee osteoarthritis patients, with less rejection response and better efficacy.

Keywords: 3D bioprinting; adipose tissue; allogenic hyaline cartilage; articular cartilage; knee; osteoarthritis.

Figure 1

Representative Images for the Surgery Procedures. An arthroscopic view of the osteochondral lesion (A); Gross appearance of the ulcer at medial condyle (B); A 3D bioprinted LCCM/MAT graft (C); The fixed graft within the osteochondral lesion (D); A representative image of measuring osteochondral lesions to generate STL file (E).

Figure 2

WOMAC Survey Results of the Participants. The significance was indicated as **** (p < 0.0001). The data are described as mean ± SD.

Figure 3

KOOS Survey Results of the Participants. The significance was indicated as **** (p < 0.0001). The data are described as mean ± SD.

Figure 4

Magnetic resonance images of the participants from pre-OP to 12 M post-OP follow-up. T2 images are placed in left column and T1 images are placed in right column. Defect site and gradual graft healing over time are indicated by white arrows.

Figure 5

MOCART Scoring Results of the Participants from 3 M post-OP to 12 M post-OP. The data are described as mean ± SD.

Figure 6

Arthroscopic Images of Knee Cartilages and Histopathology Examination at 12 M post-OP Follow-up. A second look arthroscopic image showing white de novo cartilage-like tissue (A); A closer image showing lesion site filled with hyaline-like cartilage (B); A representative histopathologic image showing de novo hyaline-like cartilage, with the cartilage thickness at defect site as indicated by black line (C); A magnified (40×) image showing differentiated chondrocytes within lacuna (D).