Engineering of osteochondral grafts by electrospinning

Thesis

Articular cartilage (AC) morbidity represents a substantial burden to global and public health, and continues to afflict millions of people in the UK. This costs the economy more than billion annually and requires approximately 80,000 knee replacements every year. To avoid these radical surgery procedures, various strategies have been recently developed to repair or restore AC through implantation of osteochondral grafts. However, their success remains limited, mainly with respect to the quality of the newly formed cartilage.

To contribute to the development of improved treatment options, this thesis explored a tissue engineering approach towards the potential use of the electrospinning technique to build osteochondral grafts. The main objectives of the research were to produce and characterise a range of electrospun membranes with various compositions, to construct three-dimensional (3D) scaffolds seeded with cells, and to study the release of therapeutic agents from electrospun materials.

Poly(lactic-co-glycolic acid) (PLGA) and Poly-epsilon-caprolactone (PCL) were the two FDA-approved polymers used to create the electrospun membranes. Collagen and hydroxyapatite were also added to increase the biocompatibility of the scaffolds. Tissue constructs were created by layering electrospun membranes with seeded sheets of human mesenchymal stem cells. Bovine Serum Albumin (BSA) and recombinant Transforming Growth Factor beta 3 (TGF-beta3) were also incorporated into the fibres and used as model proteins to study the release of therapeutic agents from the core of co-axial electrospun fibres.

Results suggest that minor alterations in composition cause gradual but significant changes in morphology, surface properties, mechanical characteristics and biocompatibility of the scaffold. The combination of electrospinning and cell sheet engineering presents a unique and effective strategy that can be used to create 3D tissue constructs with high cell density and viability. Differentiation results also indicate that intrinsic properties of PLGA and PCL affect the chondrocyte phenotype. With regard to drug delivery, BSA and TGF-beta3 were successfully incorporated into electrospun materials and subsequently released into an aqueous environment. The release profiles recorded exhibited a pronounced initial burst release that was significantly reduced by mineral deposition onto the membranes.

To conclude, this thesis presents several contributions that demonstrate the use of multilayered electrospun scaffolds as a successful approach for the generation of tissue engineered osteochondral grafts. Furthermore, this work supports the use of electrospinning as a key technology for future AC repair.

Authors: Mouthuy, P

• Publication date: 2011
• DOI: 10.5287/ora-przebprmk
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: stem cells; tissue engineering; tissue interfaces; articular cartilage; Electrospinning; biomaterials
• Subjects: Stem cells (clinical sciences); Orthopaedics; Nanostructures; Materials processing; Nanomaterials; Biomedical engineering