Long, Sheng; (2021) Digitally Defined Three Dimensional Collagen-based Scaffolds for Regenerative Cartilage Implants. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Abstract There is a clear unmet clinical need for innovative approaches to organ reconstruction and regeneration. Allografting, autologous reconstruction and prosthetics have well-known limitations. Although tissue engineering holds promise of biological substitutes for synthetic regenerative implants to replace damaged tissue and to restore its structure and functions, biofunctional scaffolds and accessible cell resources are still lacking. Collagen has been clinically used as scaffolds for tissue reconstruction for many years due its availability in large quantities, biocompatibility, biodegradability. On the other hand, 3D printing has an advantage of producing a scaffold with complex geometry, interconnected pores in varying sizes to promote cell adhesion, proliferation and migration. However, 3D printing collagen scaffolds is not trivial and suffers problems such as a slow gelation time, poor formability and mechanical properties. Adult adipose-derived mesenchymal stem cells (ADMSCs) are one of appealing cell resources for tissue regeneration and stem cell therapies due to their availability with less ethical and invasive concerns, and a great capacity of self-renewal while maintaining their multipotency. This project develops versatile collagen and its nanocomposites-based scaffolds as a platform for tissue/organ repair and regeneration through advanced 3D printing technology, especially for cartilage regeneration. A reverse 3D printing technique has been developed to manufacture the collagen and collagen/gelatin/chitosan (CGC) based composite scaffolds and collagen/PCL hybrid scaffolds with ECM-like hierarchical porous structure, enhanced mechanical properties and biological functions. Furthermore, cellular responses of using human dermal fibroblasts (HDF), the viability and chondrogenic differentiation of human adipose-derived mesenchymal stem cell (hADSCs) and rat animal model study on the printed collagen-based scaffold have been systematically studied. The hierarchical interconnected porous structure of the collagen-based scaffolds with enhanced mechanical properties will provide a micro-niche for guiding the adhesion, migration, proliferation and differentiation of human MSCs in 3D in vitro and tissue ingrowth and vascularization in vivo. Overall, collagen-based series scaffold by advanced reverse 3D printing technology hold promises for personalized and biologically responsive soft tissue implants and implantable devices with better mechanical matches and tissue integration.

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