A semi-degradable composite scaffold for articular cartilage defects

Abstract

Few options exist to replace or repair damaged articular cartilage. The optimal solution that has been suggested is a scaffold that can carry load and integrate with surrounding tissues; but such a construct has thus far been elusive. The objectives of this study were to manufacture and characterize a nondegradable hydrated scaffold. Our hypothesis was that the polymer content of the scaffold can be used to control its mechanical properties, while an internal porous network augmented with biological agents can facilitate integration with the host tissue. Using a two-step water-in-oil emulsion process a porous polyvinyl alcohol (PVA) hydrogel scaffold combined with alginate microspheres was manufactured. The scaffold had a porosity of 11-30% with pore diameters of 107-187 μm, which readily allowed for movement of cells through the scaffold. Alginate microparticles were evenly distributed through the scaffold and allowed for the slow release of biological factors. The elastic modulus (Es ) and Poisson's ratio (υ), Aggregate modulus (Ha ) and dynamic modulus (ED ) of the scaffold were significantly affected by % PVA, as it varied from 10 to 20% wt/vol. Es and υ were similar to that of articular cartilage for both polymer concentrations, while Ha and ED were similar to that of cartilage only at 20% PVA. The ability to control scaffold mechanical properties, while facilitating cellular migration suggest that this scaffold is a potentially viable candidate for the functional replacement of cartilage defects.

Keywords: cartilage; osteoarthritis; polymer; scaffold; tissue engineering.

Figure 1

Method of scaffold manufacture. A water-in-oil emulsion technique (A) was used to create the alginate microparticles. These drug-delivery particles were then added during PVA hydrogel fabrication (B) to create the final semi-degradable scaffold.

Figure 2

Using ESEM, macropores and embedded alginate microparticles were evident in the hydrated PVA scaffolds. The scaffolds had an average pore size of 147 ± 40 μm; percent porosity of these macropores ranged from 11% to 30%. Alginate microspheres had an average diameter of 15 ± 4 μm.

Figure 3

Response of scaffold to stress-relaxation tests in confined and unconfined configuration of a representative construct. The experimental data and theoretical fit as per the biphasic theory for the confined tests are illustrated. The first two ramps represent the 8% tare strain (applied in two 4% strain steps) and were not used for calculations.

Figure 4

Aggregate Modulus (H_A) and Elastic Modulus (E_S) of 10% PVA constructs and 20% PVA constructs vs. that of mature articular cartilage (n=6 samples per group). *p<0.05 vs. cartilage, †p<0.05 vs. 10% PVA

Figure 5

The cumulative release of insulin from n=6 scaffolds up to 28 days. The release profile followed an exponential curve with a half-life of 25 hours.

Figure 6

Photomicrographs of Alcian Blue-stained cells present in the center of the PVA hydrogels at (A) 20× magnification and (B) 40× magnification. After 14 days of seeding, cells were seen to migrate inward from the injection sites.