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Design and fabrication of scaffolds for cartilage applications through photopolymerization of hydrogels

Mishbak, Hussein Hadi Mossa

[Thesis]. Manchester, UK: The University of Manchester; 2019.

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Abstract

Articular cartilage is a load-bearing tissue that covers the ends of bone joints, acting as a low-friction bearing surface and a mechanical damper for the bones. Articular cartilage is a matrix-rich tissue with specialized cells (chondrocytes) that maintain the structural and functional integrity of the extracellular matrix (ECM). An important feature of cartilage is lacking self-repair ability and as a consequence, the zonal structure and cartilage functions are often irreversibly lost following trauma and disease. As a result, cartilage defects are prone to develop into predominant cartilage disease osteoarthritis (OA), characterized by loss of cartilage, pain and debilitation. The most common treatment for OA is joint replacement surgery, in which damaged joint components are replaced by artificial prosthesis. This typically reduces the pain and increases the mobility. However, over time such implants often fail and require revision surgeries. Tissue engineering has emerged as an alternative strategy to overcome the limitations of traditional therapies by replacing the damaged part of cartilage tissue with a biofabricated cartilage tissue for long-lasting periods and holds great promise as an effective treatment for cartilage repair. However, most of the approaches in this field focus on the use of single material structures, not able to mimic the real structure of cartilage. This research project focus on the design and fabrication of novel multi-material cartilage replacement by using two different hydrogels (alginate, gelatin) and a hybrid system based on the combination of both alginate and gelatin. These materials were successfully functionalized with methacrylate anhydride allowing them to be processed through UV photopolymerization. The effect of polymer concentration, methacrylated anhydride concentration and functionalization reaction time was investigated allowing to tailor rheological and viscoelastic properties. Pre-polymerized polymeric solutions were also prepared considering different concentrations of photoinitiators. Mechanical, swelling and degradation characteristics of these different systems were determined allowing to identify the most suitable compositions for each single polymer system. Additionally, the ability of each system to be used as a cartilage bioink was further investigated through live/dead assay using human chondrocyte and mesenchymal stem cells. Finally, the novel hybrid system proposed by this research was further investigated in terms of its composition (ratio between gelatin and alginate) and a detailed biological study was preformed not only to investigate the ability of this system to support cell growth and cell-cell network formation but also the ECM formation through the quantification of GAGs, Collagen and aggrecan. Results show that the developed systems can be used as bioinks, their properties can be easily tailored and that the novel hybrid system, which overcomes the main limitations of each individual system, is a promising bioink material to support cartilage formation.