The Effects of Designed Scaffold Architecture and Biodegradable Material on Chondrogenesis in vitro and in vivo.

Abstract

Poly (1, 8-octanediol-co-citric acid) (POC) is a synthetic biodegradable biocompatible elastomer that can be processed by solid freeform fabrication into 3D scaffolds for cartilage tissue engineering. We investigated the effect of designed porosity on the mechanical properties, permeability, and degradation profiles of the POC scaffolds. Increased porosity was associated with increased degradation rate, increased permeability, and decreased mechanical stiffness that also became less nonlinear.

One goal of this work was to examine the effects of pore shape and permeability of two different POC scaffold designs on matrix production, mRNA gene expression, and differentiation of chondrocytes in both in vitro and in vivo models and the consequent mechanical property changes of the scaffold/tissue constructs. We also examined the effects of collagen I gel concentration on chondrogenesis as a cell carrier and found that a lower collagen gel concentration provides a favorable microenvironment for chondrocytes. With regards to scaffold design, low permeability with a spherical pore shape better enhanced the chondrogenic performance of chondrocytes in terms of matrix production, cell phenotype, and mRNA gene expression in vitro and in vivo compared to the highly permeable scaffold with a cubical pore shape. There were higher mRNA expressions for cartilage specific proteins and matrix degradation proteins in the high permeable design in vivo, resulting in overall less sGAG retained in the high permeable scaffold compared with the low permeable scaffold.

In order to determine the scaffold material effects on cartilage regeneration, three dimensional polycaprolactone (PCL), poly (glycerol sebacate) (PGS), and POC scaffolds of the same design were physically characterized and tissue regeneration was compared to find which material would be most optimal for cartilage regeneration in vitro. POC provided the best support for cartilage regeneration while PGS was seen as the least favorable material based on mRNA expressions. PCL still provided microenvironments suitable for chondrocytes to be active, yet it seemed to cause de-differentiation of chondrocytes inside the scaffold while growing cartilage outside the scaffold.

Scaffold architectures and materials characterization and analysis in this work will provide design guidance for scaffolds to meet the mechanical and biological parameters needed for cartilage regeneration.