Self-Assembling Peptide Amphiphiles as an Adjunct to Microfracture
for Articular Cartilage Regeneration in a Rabbit Model

Nirav A Shah MD¹, Ramille M. Capito PhD², Gordon W. Nuber MD¹, Samuel I. Stupp² PhD
1. Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine
2. Institute for Bionanotechnology in Medicine (IBNAM), Northwestern University

Articular cartilage injuries have limited potential to heal back to normal hyaline cartilage.  Current interventions include microfracture, subchondral drilling, cultured chondrocytes with or without biodegradable scaffolds, and osteochondral grafting. A novel customizable three-dimensional bioactive scaffold that self-assembles into nanofibers has been developed in our lab.  Prior in vitro studies demonstrated that these PA scaffolds support human mesenchymal stem cell (MSC) viability and chondrogenic differentiation.  The purpose of this in vivo study was to assess using self-assembling PAs as an adjunct to microfracture for enhanced articular cartilage regeneration.  The null hypothesis was that there is no difference in articular cartilage regeneration between Microfracture + TGF-β1 + PA (Experimental) and Microfracture + TGF-β1 (Control).

A randomized microfracture rabbit knee model was utilized where two full thickness chondral defects 2mm2 in diameter were created in the trochlea of each knee. Sample size determination (CI>95%; 80% power; paired t-test) yielded 8 defects per group. 10 defects per group were analyzed. After surgery the rabbits were sacrificed at 12 weeks and the trochlea were harvested and assessed histologically for percent fill & O’Driscoll Scoring.

Percent tissue fill within the defect for the experimental group was significantly higher than the control group (p<0.05).   O’Driscoll scores (obtained from 3 blinded observers) indicated that using the PA as an adjunct to microfracture significantly enhances cartilage regeneration 12-weeks postop compared to the controls (p<0.05).  Type II collagen immunohistochemical staining was more evident in the experimental group.

Self-assembling PAs enhance and improve articular cartilage regeneration when used as an adjunct to microfracture.   Enhanced regeneration can be attributed to the bioactivity and 3-D nanofiber self-assembly of the PA, which may help to localize and retain exogenous and endogenous growth factors within the defect.  This is the first in vivo report to our knowledge that utilizes self assembling PAs and microfracture for improved articular cartilage regeneration.