Purpose

To demonstrate comparative KOOS Overall outcomes of an interpositional knee meniscus endoprosthesis versus non-surgical controls in the treatment of persistent post meniscectomy knee pain.

Methods and Materials

242 patients enrolled in a pooled population, randomized controlled trial (RCT) and single-arm study, comparing the investigational device to non-surgical standard of care. Of the first 100 patients enrolled, whose follow-up has exceeded 12 months, 65 patients were treated with the interpositional endoprosthesis device, and 35 were treated non-surgically. Validated KOOS scores at baseline, 6-week, 6-month, and 12-month time points were obtained from all patients. A “clinically significant improvement” was considered to be an increase of 20 KOOS points, (Roos et al.2003). The cohorts were compared at each time point using a two tailed t-test. All baseline cohort demographics and KOOS Overall score were not statistically different (p>0.05).

Results

Improvement in KOOS Overall for the investigational and control cohorts at 6-months and 12-months were 23.0 and 7.6 points, and 28.8 and 11.3 points, respectively (Figure 1). These data show a statistically significant improvement, above the clinically meaningful threshold, in the investigational arm versus the control arm as early as 6 months (p<0.001) and continues through the 12-month timepoint (p<0.001).

At 12 months, 3 (4.6%) investigational vs. 5 (14.3%) control patients were deemed study failures, due to removal of the investigational device, or due to non-surgical control patients requiring surgical intervention, At 12 months, more patients progressed to knee arthroplasty procedures in the non-surgical, control group (n=4, 11.4%) than in the surgical, investigational group (n=1, 1.5%).

Conclusion

These early one year follow-up results of efficacy KOOS Overall score are encouraging. Further study of the clinical outcomes of these patients and their adverse events is ongoing, with long-term results of both the randomized controlled trial and the single-arm study to be reported in the future.

Purpose

Some aragonite-based scaffolds exhibit osteoconductive properties and are considered useful bone repair scaffolds. The purpose of this study was to evaluate the in vitro osteotransductive potential of the bone phase of a novel aragonite-based bi-phasic osteochondral scaffold (Agili-C^TM, CartiHeal Ltd.).

Methods and Materials

Adult human bone-marrow derived mesenchymal stem cells (BM-MSCs) grown in osteogenic medium (Lonza Group Ltd., Basel, Switzerland) were assessed. The study was designed to compare the effect of the bone phase of the Agili-C implant, a coral-derived aragonite scaffold on human BM-MSCs compared to cells grown in an optimal differentiation medium without scaffolds. Analyses were performed at several time intervals: 3, 7, 14, 21, 28- and 42-days post-seeding. Osteogenic differentiation was assessed by morphological characterisation using light microscopy after Alizarin red and von Kossa staining, and scanning electron microscopy. The transcript levels of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), bone gamma-carboxyglutamate (BGLAP), osteonectin (SPARC) and osteopontin (SPP1) were determined by quantitative PCR. Proliferation was assessed.

Results

Cell cultures of human BM-MSC's demonstrate that the bone phase of the bi-phasic aragonite-based scaffold supports bone formation through enhanced proliferation and osteogenic differentiation of BM-MSCs at both the molecular and histological levels. The scaffold was colonized by differentiating MSCs, suggesting its suitability for incorporation into bone voids to accelerate bone healing, remodelling and regeneration. The mechanism of direct bone formation involves scaffold surface modification with de novo production of calcium phosphate deposits, as revealed by energy dispersive spectroscopy analyses. Scanning the scaffold surface revealed the presence of a microstructure deposit exhibiting a unique morphology (Figure 1) supporting cell attachment (Figure 2).

Conclusion

This implant may promote a fast growth of high-quality bone during the repair of osteochondral lesions. The implant seemed to enhance proliferation of MSCs and formation of multilayer cultures onto its surface.