Publicação
Tissue engineering approaches in a musculoskeletal disease scenario
| Resumo: | Meniscus injuries are among the most frequent orthopedic injuries that can require surgical intervention. Management of meniscus injuries is often challenging and partially unresolved. In this context, tissue engineering strategies are emerging as a reliable solution to repair or regenerate diseased/damaged tissues as it involves the use of cells, scaffolds and bioactive agents, alone or in combination. Given the critical roles of microstructure on the performance of scaffolds, characterization of the micro-structure is indispensable. The acquisition parameters of Micro-computed tomography (micro-CT) are user-dependent, and may have significant effects on the obtained results. Patientspecificity and suturability of the scaffolds are two of the main surgical requirements which are for the dimensional fit of the implant, fixation of the implant, and avoidance of the post-operative extrusion of the implant. In this doctoral work, the scientific and clinical challenges mentioned above were addressed. The 3D cellular density of human meniscus was investigated, and to the best of our knowledge, this is the first study on 3D quantification of the cells in the human meniscus. These valuable insights on the 3D cellularity of the meniscus can support the cell-based strategies. Regarding the micro-CT characterization of the scaffolds, we have showed that the acquisition parameters could statistically significantly affect the quantified micro-structural parameters. This is the only study examining the effects of such a wide range of micro-CT acquisition scenarios on the 3D analysis of scaffolds. Herein, we propose novel Entrapped in Cage (EiC) scaffolds of 3D-printed polycaprolactone (PCL) and porous silk fibroin for meniscus tissue engineering, seeded with human stem cells or human meniscocytes, and characterized in vitro and in vivo. To address the suturability of scaffolds, we proposed a novel suturable regenerated silk fibroin scaffolds reinforced with 3D-printed PCL mesh. Results showed that the suture retention strength increased significantly. The tissue infiltration and formation of new blood vessels were assessed by means of performing an in vivo subcutaneous implantation. To address, the patient-specificity of meniscal scaffolds, we established a reverseengineering method to produce 3D-printed patient-specific meniscal scaffolds using the patients’ knee magnetic resonance imaging (MRI) data. This thesis is a step forward on the research dealing with meniscus tissue engineering, and brings us a step closer to the development of patient-specific meniscal implants and translation of personalized tissue engineering into daily clinical approaches when treatment of meniscus lesions is envisioned. |
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| Autores principais: | Cengiz, I. F. |
| Assunto: | Meniscus Patient-specific implant Cellularity 3D-Printing Scaffold Micro-CT Tissue engineering Menisco Implante específico do paciente Celularidade Impressão 3D Matriz tridimensional porosa Micro-CT Engenharia de tecidos |
| Ano: | 2019 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Meniscus injuries are among the most frequent orthopedic injuries that can require surgical intervention. Management of meniscus injuries is often challenging and partially unresolved. In this context, tissue engineering strategies are emerging as a reliable solution to repair or regenerate diseased/damaged tissues as it involves the use of cells, scaffolds and bioactive agents, alone or in combination. Given the critical roles of microstructure on the performance of scaffolds, characterization of the micro-structure is indispensable. The acquisition parameters of Micro-computed tomography (micro-CT) are user-dependent, and may have significant effects on the obtained results. Patientspecificity and suturability of the scaffolds are two of the main surgical requirements which are for the dimensional fit of the implant, fixation of the implant, and avoidance of the post-operative extrusion of the implant. In this doctoral work, the scientific and clinical challenges mentioned above were addressed. The 3D cellular density of human meniscus was investigated, and to the best of our knowledge, this is the first study on 3D quantification of the cells in the human meniscus. These valuable insights on the 3D cellularity of the meniscus can support the cell-based strategies. Regarding the micro-CT characterization of the scaffolds, we have showed that the acquisition parameters could statistically significantly affect the quantified micro-structural parameters. This is the only study examining the effects of such a wide range of micro-CT acquisition scenarios on the 3D analysis of scaffolds. Herein, we propose novel Entrapped in Cage (EiC) scaffolds of 3D-printed polycaprolactone (PCL) and porous silk fibroin for meniscus tissue engineering, seeded with human stem cells or human meniscocytes, and characterized in vitro and in vivo. To address the suturability of scaffolds, we proposed a novel suturable regenerated silk fibroin scaffolds reinforced with 3D-printed PCL mesh. Results showed that the suture retention strength increased significantly. The tissue infiltration and formation of new blood vessels were assessed by means of performing an in vivo subcutaneous implantation. To address, the patient-specificity of meniscal scaffolds, we established a reverseengineering method to produce 3D-printed patient-specific meniscal scaffolds using the patients’ knee magnetic resonance imaging (MRI) data. This thesis is a step forward on the research dealing with meniscus tissue engineering, and brings us a step closer to the development of patient-specific meniscal implants and translation of personalized tissue engineering into daily clinical approaches when treatment of meniscus lesions is envisioned. |
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