A novel osteochondral composite consisting of a self-assembling peptide hydrogel and 3D printed polycaprolactone scaffold : potential for articular cartilage repair

Abstract

Degenerative diseases, such as osteoarthritis, and traumatic injuries are both prominent causes of cartilage defects. Due to its avascular nature, adult human cartilage displays limited capacity for regeneration. Current surgical treatments to induce a spontaneous repair response rely on access to the subchondral bone region. These procedures result in fibrocartilage generation, as opposed to hyaline cartilage, that is variable in structure, composition, and durability. Furthermore, the success rates of these surgeries are also variable. Deficiencies in these cartilage repair methods motivate investigation into a tissue engineering means of repairing or regenerating cartilage. Various composites designed to emulate a cartilage and bone interface are under investigation. The aim of this study was to conceive a means of integrating a chondrocyte-seeded peptide hydrogel with an interconnected porous 3D printed polycaprolactone (PCL) scaffold to create a novel osteochondral construct. The self-assembling peptide hydrogel has been shown to provide an environment that maintains chondrocyte phenotype and viability. Furthermore, the 3D scaffold fosters extracellular matrix production and chondrocyte division. PCL is a bioresorbable and biocompatible polymer scaffold, capable of supporting the attachment of both osteogenic and chondrogenic cells and cell-specific extracellular matrix production, that can be integrated with the peptide hydrogel to constitute an osteochondral construct. A primary advantage of the 3D printing technology is the ability to control the microarchitecture and macroarchitecture of the PCL scaffold in a layer by layer fashion. Integration of the peptide hydrogel into the porous PCL scaffold may be enhanced by creating a gradient of porosity

(cont.) at the interface of the materials, while the lower portion of the PCL scaffold would possess a scaffold microarchitecture optimized for bone ingrowth. Through the use of an agarose mold, the construction of an osteochondral composite consisting of the chondrocyte-seeded peptide hydrogel and porous PCL scaffold was made possible in an integrated, controlled, and repeatable fashion. PCL was found to act as an inert material with regard to chondrocyte behavior, as chondrocyte morphology, viability, extracellular matrix production, and biosynthesis rates proved to be analogous to those seen in the chondrocyte-seeded peptide hydrogel only systems previously studied. A distinction in the microarchitecture of the PCL scaffold, 70% porosity versus 90% porosity, was not found to markedly impact chondrocyte behavior in the peptide hydrogel. The efficacy of the peptide hydrogel material selection was illustrated by comparison to a chondrocyte-seeded agarose hydrogel and PCL composite, with an agarose hydrogel serving as a more traditional means of studying chondrocyte behavior. Biochemical, mechanical, and histological characterization of the peptide hydrogel and porous PCL construct delineate the potential use of this composite for osteochondral defect repair. Future studies may involve dynamic compression of the composite to stimulate extracellular matrix synthesis and accumulation, and in vivo investigations to demonstrate the clinical impacts of such a construct on cartilage repair.