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Design and fabrication of a novel bioactive composite scaffold to induce anterior cruciate ligament regeneration

Choreno Machain, Tania; (2021) Design and fabrication of a novel bioactive composite scaffold to induce anterior cruciate ligament regeneration. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Introduction: Anterior cruciate ligament (ACL) injuries are one of the most common sports injuries. The injury entails devastating consequences in a person’s quality of life and leads to an early onset of osteoarthritis (OA). The current treatment of choice is associated with an unacceptable rate of donor-site morbidities due to harvesting a tendon from the already injured limb to use as a graft for the surgical reconstruction, but the alternative conservative treatment is associated with up to 87% development of post-traumatic OA. Although various approaches exist, there is currently no ideal choice of graft that could ensure knee stability and address the joint inflammatory state. Hypothesis: The addition of a biomimetic coating to the only clinically accepted synthetic graft’s material will support ligament resident cells growth and enhance ligament-like extracellular matrix deposition that would contribute to ligament healing. Methods: PET fibres were modified in a two-step process. First, O2 plasma was used to activate the surface. Next, a bioactive coating was added. Biocompatibility tests under physiologically relevant static and dynamic conditions were executed with mesenchymal stem cells (MSCs) and patient-derived ACL cells. Results: PET surface was effectively activated by a 1-min O2 plasma exposure. The 1% chitosan glycidyl methacrylate (CS-g-GMA) / 1% hyaluronic acid (HA) coating of an O2 plasma pre-treated PET fibrous scaffold provided the maximum enhancement of collagen deposition across all the studies conducted. The effect is sustained in the context of strenuous physical activity and is further increased by low-intensity pulsed ultrasound (LIPUS) treatment at a frequency of 1 MHz, a duty cycle (DC) of 50% and an intensity of 0.5 W/cm2. The scaffold proved appropriate for the interaction with a MSC line and patient-derived ACL cells from individuals of different ages and gender. Conclusion: The biocomposite scaffold designed and developed in this thesis combines straightforward methodology, approved materials already in clinical use for different purposes and a favourable response to safe readily available rehabilitation options to improve the outcomes for ligament regeneration.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Design and fabrication of a novel bioactive composite scaffold to induce anterior cruciate ligament regeneration
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
URI: https://discovery.ucl.ac.uk/id/eprint/10140664
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