{"id":{"repo_id":"exeter","oai_identifier":"oai:figshare.com:article/32868998"},"canonical_url":"https://search.dev.ndltd.org/etd/exeter/oai:figshare.com:article/32868998","repository":{"repo_id":"exeter","name":"University of Exeter","base_url":"https://api.figshare.com/v2/oai"},"display":{"title":"A patient specific total disc replacement to treat degenerative disc disease","abstract":"Low back pain remains the leading cause of disability worldwide, most often arising from degeneration of the intervertebral discs (IVD). When conservative treatments fail, surgical replacement with an artificial total disc replacement (TDR) is often required. However, despite decades of refinement, current TDRs are unable to fully replicate the complex mechanical behaviour of the native intervertebral disc. As a result, suboptimal movement, adjacent segment degeneration, and chronic pain remain prevalent. Tissue engineered constructs provide a potential solution to these long-term side effects and unfavourable patient outcomes by replacing like with like, restoring both the biological and mechanical functions of the IVD. This thesis aimed to develop and validate a tissue-engineered total disc replacement that reproduces the mechanical environment of the native L4/L5 intervertebral disc and evaluate its capacity to support regenerative cell responses under physiological cyclic loads. Finite element (FE) modelling was used as a prescriptive rather than descriptive tool to guide the design of a scaffold-based TDR capable of matching physiological stiffness in compression, flexion/extension, lateral bending, and axial rotation. A version of this geometry was then fabricated using an inkjet printed plastic and polydimethylsiloxane (PDMS) and tested in a six-axis spine simulator to validate the FE simulations. To relate the mechanics of this TDR scaffold to potential cellular responses, cyclic strains of 4–10% were applied to human mesenchymal stem cell (hMSC)-seeded membranes to quantify changes in extracellular matrix composition. These findings were then compared with strain distributions predicted across the scaffold’s fibres, linking the modelled mechanical environment to expected cell behaviour. A full-size scaffold was subsequently fabricated from a 3D-printed elastomer and seeded with hMSCs, providing a foundation for future studies investigating tissue regeneration under physiological loading. This study demonstrated that the proposed geometry could reproduce the stiffness profile of the native L4/L5 intervertebral disc in compression, flexion/extension, lateral bending, and axial rotation by incorporating key anatomical features of the L4/L5 segment, while accounting for fabrication constraints using two components with elastic material properties. This modelling framework can be readily adapted to other lumbar spinal levels or material combinations, providing a foundation for patient-specific design. Cyclic strain experiments (0–10%) with hMSC-seeded membranes produced varied extracellular matrix deposition, with the proportion of Tenomodulin positive cells and Collagen II increasing, and Tenascin-C and Collagen Type I decreasing. This highlights the challenges of quantifying matrix deposition in multilayered cell surfaces using immunofluorescent imaging. These observations emphasise the need for refined analytical methods and longer-term studies to accurately evaluate the influence of physiological strain on matrix synthesis and cell phenotype. Complementary FE strain mapping predicted physiological cell-perceived strains of approximately 1% across all movements, with modest variation between lamellae ranging from 0.77% to 1.15%. These values are lower than those commonly used in in-vitro differentiation protocols, providing context for designing physiologically grounded loading regimens and informing expectations for cellular responses within larger constructs. Building on these findings, surface treatment and cell-seeding strategies were optimised to achieve cell attachment throughout a 3D printed full-size scaffold, demonstrating the feasibility of creating cell-laden, anatomical-scale constructs for future tissue engineering studies.<p></p>","abstract_html":"Low back pain remains the leading cause of disability worldwide, most often arising from degeneration of the intervertebral discs (IVD). When conservative treatments fail, surgical replacement with an artificial total disc replacement (TDR) is often required. However, despite decades of refinement, current TDRs are unable to fully replicate the complex mechanical behaviour of the native intervertebral disc. As a result, suboptimal movement, adjacent segment degeneration, and chronic pain remain prevalent. Tissue engineered constructs provide a potential solution to these long-term side effects and unfavourable patient outcomes by replacing like with like, restoring both the biological and mechanical functions of the IVD. This thesis aimed to develop and validate a tissue-engineered total disc replacement that reproduces the mechanical environment of the native L4/L5 intervertebral disc and evaluate its capacity to support regenerative cell responses under physiological cyclic loads. Finite element (FE) modelling was used as a prescriptive rather than descriptive tool to guide the design of a scaffold-based TDR capable of matching physiological stiffness in compression, flexion/extension, lateral bending, and axial rotation. A version of this geometry was then fabricated using an inkjet printed plastic and polydimethylsiloxane (PDMS) and tested in a six-axis spine simulator to validate the FE simulations. To relate the mechanics of this TDR scaffold to potential cellular responses, cyclic strains of 4–10% were applied to human mesenchymal stem cell (hMSC)-seeded membranes to quantify changes in extracellular matrix composition. These findings were then compared with strain distributions predicted across the scaffold’s fibres, linking the modelled mechanical environment to expected cell behaviour. A full-size scaffold was subsequently fabricated from a 3D-printed elastomer and seeded with hMSCs, providing a foundation for future studies investigating tissue regeneration under physiological loading. This study demonstrated that the proposed geometry could reproduce the stiffness profile of the native L4/L5 intervertebral disc in compression, flexion/extension, lateral bending, and axial rotation by incorporating key anatomical features of the L4/L5 segment, while accounting for fabrication constraints using two components with elastic material properties. This modelling framework can be readily adapted to other lumbar spinal levels or material combinations, providing a foundation for patient-specific design. Cyclic strain experiments (0–10%) with hMSC-seeded membranes produced varied extracellular matrix deposition, with the proportion of Tenomodulin positive cells and Collagen II increasing, and Tenascin-C and Collagen Type I decreasing. This highlights the challenges of quantifying matrix deposition in multilayered cell surfaces using immunofluorescent imaging. These observations emphasise the need for refined analytical methods and longer-term studies to accurately evaluate the influence of physiological strain on matrix synthesis and cell phenotype. Complementary FE strain mapping predicted physiological cell-perceived strains of approximately 1% across all movements, with modest variation between lamellae ranging from 0.77% to 1.15%. These values are lower than those commonly used in in-vitro differentiation protocols, providing context for designing physiologically grounded loading regimens and informing expectations for cellular responses within larger constructs. Building on these findings, surface treatment and cell-seeding strategies were optimised to achieve cell attachment throughout a 3D printed full-size scaffold, demonstrating the feasibility of creating cell-laden, anatomical-scale constructs for future tissue engineering studies.&lt;p&gt;&lt;/p&gt;","abstract_has_math":false,"creators":["Samuel Rudd (21040424)"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2026,"date_issued":"2026-07-20T00:00:00Z","date_published":"2026-07-20T00:00:00Z","updated_at":"2026-07-27T19:32:18Z","subjects":["Tissue Engineering","Biomechanics","Intervertebral Disc","Finite Element Analysis"],"languages":[],"rights":["All rights reserved","Open Access after 2029-07-01"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["10779/exe.32868998.v1"],"render_values":[{"text":"10779/exe.32868998.v1","href":null,"code":true}]}]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Samuel Rudd (21040424)"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2026-07-20T00:00:00Z"]},{"key":"dc:relation","label":"Dc Relation","values":["https://figshare.com/articles/thesis/A_patient_specific_total_disc_replacement_to_treat_degenerative_disc_disease/32868998"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Tissue Engineering","Biomechanics","Intervertebral Disc","Finite Element Analysis"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["All rights reserved","Open Access after 2029-07-01"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["10779/exe.32868998.v1"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Low back pain remains the leading cause of disability worldwide, most often arising from degeneration of the intervertebral discs (IVD). When conservative treatments fail, surgical replacement with an artificial total disc replacement (TDR) is often required. However, despite decades of refinement, current TDRs are unable to fully replicate the complex mechanical behaviour of the native intervertebral disc. As a result, suboptimal movement, adjacent segment degeneration, and chronic pain remain prevalent. Tissue engineered constructs provide a potential solution to these long-term side effects and unfavourable patient outcomes by replacing like with like, restoring both the biological and mechanical functions of the IVD. This thesis aimed to develop and validate a tissue-engineered total disc replacement that reproduces the mechanical environment of the native L4/L5 intervertebral disc and evaluate its capacity to support regenerative cell responses under physiological cyclic loads. Finite element (FE) modelling was used as a prescriptive rather than descriptive tool to guide the design of a scaffold-based TDR capable of matching physiological stiffness in compression, flexion/extension, lateral bending, and axial rotation. A version of this geometry was then fabricated using an inkjet printed plastic and polydimethylsiloxane (PDMS) and tested in a six-axis spine simulator to validate the FE simulations. To relate the mechanics of this TDR scaffold to potential cellular responses, cyclic strains of 4–10% were applied to human mesenchymal stem cell (hMSC)-seeded membranes to quantify changes in extracellular matrix composition. These findings were then compared with strain distributions predicted across the scaffold’s fibres, linking the modelled mechanical environment to expected cell behaviour. A full-size scaffold was subsequently fabricated from a 3D-printed elastomer and seeded with hMSCs, providing a foundation for future studies investigating tissue regeneration under physiological loading. This study demonstrated that the proposed geometry could reproduce the stiffness profile of the native L4/L5 intervertebral disc in compression, flexion/extension, lateral bending, and axial rotation by incorporating key anatomical features of the L4/L5 segment, while accounting for fabrication constraints using two components with elastic material properties. This modelling framework can be readily adapted to other lumbar spinal levels or material combinations, providing a foundation for patient-specific design. Cyclic strain experiments (0–10%) with hMSC-seeded membranes produced varied extracellular matrix deposition, with the proportion of Tenomodulin positive cells and Collagen II increasing, and Tenascin-C and Collagen Type I decreasing. This highlights the challenges of quantifying matrix deposition in multilayered cell surfaces using immunofluorescent imaging. These observations emphasise the need for refined analytical methods and longer-term studies to accurately evaluate the influence of physiological strain on matrix synthesis and cell phenotype. Complementary FE strain mapping predicted physiological cell-perceived strains of approximately 1% across all movements, with modest variation between lamellae ranging from 0.77% to 1.15%. These values are lower than those commonly used in in-vitro differentiation protocols, providing context for designing physiologically grounded loading regimens and informing expectations for cellular responses within larger constructs. Building on these findings, surface treatment and cell-seeding strategies were optimised to achieve cell attachment throughout a 3D printed full-size scaffold, demonstrating the feasibility of creating cell-laden, anatomical-scale constructs for future tissue engineering studies.<p></p>"]},{"key":"dc:title","label":"Title","values":["A patient specific total disc replacement to treat degenerative disc disease"]}]}],"canonical_facts":{"dc:creator":["Samuel Rudd (21040424)"],"dc:date":["2026-07-20T00:00:00Z"],"dc:description":["Low back pain remains the leading cause of disability worldwide, most often arising from degeneration of the intervertebral discs (IVD). When conservative treatments fail, surgical replacement with an artificial total disc replacement (TDR) is often required. However, despite decades of refinement, current TDRs are unable to fully replicate the complex mechanical behaviour of the native intervertebral disc. As a result, suboptimal movement, adjacent segment degeneration, and chronic pain remain prevalent. Tissue engineered constructs provide a potential solution to these long-term side effects and unfavourable patient outcomes by replacing like with like, restoring both the biological and mechanical functions of the IVD. This thesis aimed to develop and validate a tissue-engineered total disc replacement that reproduces the mechanical environment of the native L4/L5 intervertebral disc and evaluate its capacity to support regenerative cell responses under physiological cyclic loads. Finite element (FE) modelling was used as a prescriptive rather than descriptive tool to guide the design of a scaffold-based TDR capable of matching physiological stiffness in compression, flexion/extension, lateral bending, and axial rotation. A version of this geometry was then fabricated using an inkjet printed plastic and polydimethylsiloxane (PDMS) and tested in a six-axis spine simulator to validate the FE simulations. To relate the mechanics of this TDR scaffold to potential cellular responses, cyclic strains of 4–10% were applied to human mesenchymal stem cell (hMSC)-seeded membranes to quantify changes in extracellular matrix composition. These findings were then compared with strain distributions predicted across the scaffold’s fibres, linking the modelled mechanical environment to expected cell behaviour. A full-size scaffold was subsequently fabricated from a 3D-printed elastomer and seeded with hMSCs, providing a foundation for future studies investigating tissue regeneration under physiological loading. This study demonstrated that the proposed geometry could reproduce the stiffness profile of the native L4/L5 intervertebral disc in compression, flexion/extension, lateral bending, and axial rotation by incorporating key anatomical features of the L4/L5 segment, while accounting for fabrication constraints using two components with elastic material properties. This modelling framework can be readily adapted to other lumbar spinal levels or material combinations, providing a foundation for patient-specific design. Cyclic strain experiments (0–10%) with hMSC-seeded membranes produced varied extracellular matrix deposition, with the proportion of Tenomodulin positive cells and Collagen II increasing, and Tenascin-C and Collagen Type I decreasing. This highlights the challenges of quantifying matrix deposition in multilayered cell surfaces using immunofluorescent imaging. These observations emphasise the need for refined analytical methods and longer-term studies to accurately evaluate the influence of physiological strain on matrix synthesis and cell phenotype. Complementary FE strain mapping predicted physiological cell-perceived strains of approximately 1% across all movements, with modest variation between lamellae ranging from 0.77% to 1.15%. These values are lower than those commonly used in in-vitro differentiation protocols, providing context for designing physiologically grounded loading regimens and informing expectations for cellular responses within larger constructs. Building on these findings, surface treatment and cell-seeding strategies were optimised to achieve cell attachment throughout a 3D printed full-size scaffold, demonstrating the feasibility of creating cell-laden, anatomical-scale constructs for future tissue engineering studies.<p></p>"],"dc:identifier":["10779/exe.32868998.v1"],"dc:relation":["https://figshare.com/articles/thesis/A_patient_specific_total_disc_replacement_to_treat_degenerative_disc_disease/32868998"],"dc:rights":["All rights reserved","Open Access after 2029-07-01"],"dc:subject":["Tissue Engineering","Biomechanics","Intervertebral Disc","Finite Element Analysis"],"dc:title":["A patient specific total disc replacement to treat degenerative disc disease"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T19:32:18Z"}