Development of a multi-material and multi-scale 3D bioprinted scaffold for osteochondral tissue engineering

Abstract

Osteochondral tissue is a complex, hierarchical, and multi-material structure composed of articular cartilage and subchondral bone which aids in the lubrication of joints and load transmission during movement. When trauma or disease impacts the tissue, the repair and regenerative response is poor due to the avascular nature of cartilage tissue. Thus, the tissue either does not heal or forms mechanically inferior fibrocartilage. Due to an ageing worldwide population the numbers of patients suffering from degenerative diseases is increasing. Current clinical therapies are ineffective in halting the decline in tissue function resulting in severe pain and restriction in movement. New therapies based on tissue engineering and additive manufacturing are being explored and offer the possibility of regenerating the damaged tissue. This thesis presents the development of a multi-material and multi-scale scaffold fabricated using additive manufacturing and electrospinning. A state-of-the-art literature review is provided discussing the latest strategies in tissue engineering, biomaterials, and additive manufacturing. This informs the development of the scaffold. The thesis presents four main concepts in the realisation of an osteochondral scaffold comprised of a bone and cartilage region. Engineering functional microstructures and mechanical properties into the polycaprolactone scaffold was achieved by characterising the material extrusion process using in situ synchrotron x-ray diffraction. Improved mechanical properties could be achieved by printing at lower temperatures and higher screw-rates due to an increase in crystal volume fraction and anisotropy. Bioactive ceramics; hydroxyapatite and tri-calcium phosphate, electroactive materials; multi-walled carbon nanotubes and polyaniline, and silk microparticles were explored for an osteogenic and mechanically stable bone region. The results indicate that hydroxyapatite, multi-walled carbon nanotubes, and silk microparticles are biocompatible and exhibit osteogenic properties. Electrospinning was utilised to incorporate nanoscale fibres within the structure to mimic the extracellular matrix. Highly aligned fibres were observed due to the printed scaffold acting as a patterned gap collector. This promoted alignment of cells. An antibacterial and tissue regenerative biomaterial was developed as the electrospun component of the scaffold and showed increased cell proliferation. Finally, a photocurable dual-crosslinkable alginate and gelatin hydrogel was developed as a bioink for the cartilage region of the scaffold. The results indicate phenotype stability in the chondrocytes and production of extracellular matrix. This research shows the development of a multi-material and multi-scale 3D printed scaffold with promising attributes for application in osteochondral tissue engineering.

Date of Award	28 Aug 2020
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Judith Hoyland (Supervisor), Wajira Mirihanage (Supervisor) & Paulo Jorge Da Silva Bartolo (Supervisor)