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Design and development of new ligament implants

Ciudad, Elisa Roldan (2018) Design and development of new ligament implants. Doctoral thesis (PhD), Manchester Metropolitan University.

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Abstract

The anterior cruciate ligament (ACL) is one of the most frequently injured ligaments of the knee. It provides joint stability by constraining anterior tibial translations or internal rotations. This ligament suffers from one of the highest injury rates and, due to the fact that it has very poor healing properties, in many cases requires surgery to be reconstructed. Nowadays the “gold standard” for surgical intervention is to reconstruct the ACL from autografts, but this procedure generates problems such as muscle weakness related to the donor site, or graft site morbidity, therefore other grafts solutions should be investigated. The aim of this thesis was to design, manufacture and test tissue engineered prototypes that could be used for surgical reconstruction of the ACL with comparable mechanical behaviour and nano and micro morphology to the native ACL. The in vivo mechanical behaviour of the ACL was investigated during a range of daily activities to understand its failure mechanisms and obtain the mechanical specifications to design and assess the new ACL prototypes. Currently, solely mechanical properties such as Young’s modulus or ultimate tensile strength are used to determine the suitability of an ACL implant, however, the work for this thesis has shown that other aspects including dynamic loading and shear loading are crucial for accurately replicating the in vivo mechanical behaviour of the ACL. Electrospinning was shown to offer great potential for manufacturing ACL implants with scaffolds of fibre diameter and orientation mimicking the collagen fibres in the extracellular matrix (ECM) of the native ACL. These biomimetic scaffolds can promote cell growth and would enhance mechanical properties. The suitability of two different polymers (a natural polymer: gelatin and a synthetic polymer: polyvinyl alcohol, PVA) were tested as potential ACL scaffolds: morphologically, topographically, mechanically and chemically through degradation assays. The optimisation of solution and process parameters was essential with the aim of creating scaffolds with mechanical properties and morphologies comparable to the native ACL, all crucial aspects that were missing from the current literature in this field. To date most of the experiments with electrospinning were manufactured 2D scaffolds, which does not represent the real three dimensional structure of the ACL. Only four researchers have worked on creating 3D structures from 2D electrospun scaffolds. However, none of them managed to produce morphology nor mechanical behaviour mimicking the natural ACL. Moreover, no comparison of 2D and multiple different 3D structures was performed before the work in this thesis. This PhD establishes the fundamentals for designing and manufacturing biomimetic ACL prototypes, which could be used as a baseline for cell testing, animal models and at the final stage clinical trials.

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