Publicação
Magnetic nanoparticles in the engineering of hybrid structures for cell and tissue engineering
| Resumo: | Organ shortages remain one of the most critical challenges in modern medicine, leading to countless preventable deaths worldwide. These shortages primarily result from the limited pool of eligible donors, as deaths from aging, disease, or trauma rarely meet criteria for organ recovery. Additional barriers, such as recipient–donor compatibility, anatomical mismatches, and geographic distances, further restrict transplant opportunities. Tissue Engineering (TE) offers a promising path to alleviate these shortages by developing organ and tissue substitutes that replicate native structure and function. Central to this approach are living cells, which possess unique capacities to create tissues and orchestrate biochemical signals far beyond the capabilities of conventional materials or devices. However, traditional cell delivery methods, such as bolus injections, often suffer from poor localization, limited durability at the target site, and suboptimal cell survival rates. This PhD thesis investigates innovative strategies for more effective cell-based therapies using both free cells and cells confined within micro- and macroscale, tissue-mimetic hydrogels. By incorporating magnetic nanoparticles, we introduced additional therapeutic functionalities. In particular, we evaluated core manganese ferrite nanoparticles coated with Ba0.85Ca0.15Zr0.1Ti0.9O3 (BCZT) piezoelectric shells for their magnetoelectric (ME) properties: under cyclic magnetic stimulation, these composite particles accelerated the osteogenic differentiation of human adipose-derived stem cell spheroids, achieving calcium-phosphorus molar ratio of 1.67, consistent with that of natural hydroxyapatite. In a subsequent study, cells were encapsulated in human-derived microgels formulated from methacryloyl-modified platelet lysate (PLMA), a protein- and growth factor-rich matrix that supported cell viability during delivery. Incorporating collagenase into these microgels provided precise, controlled cell release, addressing a key limitation of conventional microgel systems. Injectability and performance were validated using porcine tissue defects and combining magnetic nanoparticles with these carriers, thus opening possibilities for target delivery, remote guidance, microgel assembly and imaging applications. Finally, we engineered large-scale hydrogels for cell delivery, addressing the challenge of nutrient and oxygen diffusion by integrating magnetic nanoparticles and collagenase into microgels. Guided by external magnetic fields, these microgels sculpted hollow, perfusable channels within bulk hydrogels, supporting endothelial cell adhesion and fostering injectable, vascularized tissue constructs. Altogether, this research presents a suite of advanced therapeutic strategies that leverage cellular function across multiple length scales, offer remote controllability, and address crucial limitations in current transplantation and tissue engineering practices. These innovations hold significant promise for reducing the global impact of organ shortages. |
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| Autores principais: | Mendes, Maria Cândida Balão |
| Assunto: | Tissue engineering Magnetoelectric nanoparticles Spheroids Bone differentiation Hydrogels Cell delivery system Magnetic nanoparticles Magneto-enzymatic microgels Vascularization Regenerative medicine |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade de Aveiro |
| Idioma: | inglês |
| Origem: | RIA - Repositório Institucional da Universidade de Aveiro |
| Resumo: | Organ shortages remain one of the most critical challenges in modern medicine, leading to countless preventable deaths worldwide. These shortages primarily result from the limited pool of eligible donors, as deaths from aging, disease, or trauma rarely meet criteria for organ recovery. Additional barriers, such as recipient–donor compatibility, anatomical mismatches, and geographic distances, further restrict transplant opportunities. Tissue Engineering (TE) offers a promising path to alleviate these shortages by developing organ and tissue substitutes that replicate native structure and function. Central to this approach are living cells, which possess unique capacities to create tissues and orchestrate biochemical signals far beyond the capabilities of conventional materials or devices. However, traditional cell delivery methods, such as bolus injections, often suffer from poor localization, limited durability at the target site, and suboptimal cell survival rates. This PhD thesis investigates innovative strategies for more effective cell-based therapies using both free cells and cells confined within micro- and macroscale, tissue-mimetic hydrogels. By incorporating magnetic nanoparticles, we introduced additional therapeutic functionalities. In particular, we evaluated core manganese ferrite nanoparticles coated with Ba0.85Ca0.15Zr0.1Ti0.9O3 (BCZT) piezoelectric shells for their magnetoelectric (ME) properties: under cyclic magnetic stimulation, these composite particles accelerated the osteogenic differentiation of human adipose-derived stem cell spheroids, achieving calcium-phosphorus molar ratio of 1.67, consistent with that of natural hydroxyapatite. In a subsequent study, cells were encapsulated in human-derived microgels formulated from methacryloyl-modified platelet lysate (PLMA), a protein- and growth factor-rich matrix that supported cell viability during delivery. Incorporating collagenase into these microgels provided precise, controlled cell release, addressing a key limitation of conventional microgel systems. Injectability and performance were validated using porcine tissue defects and combining magnetic nanoparticles with these carriers, thus opening possibilities for target delivery, remote guidance, microgel assembly and imaging applications. Finally, we engineered large-scale hydrogels for cell delivery, addressing the challenge of nutrient and oxygen diffusion by integrating magnetic nanoparticles and collagenase into microgels. Guided by external magnetic fields, these microgels sculpted hollow, perfusable channels within bulk hydrogels, supporting endothelial cell adhesion and fostering injectable, vascularized tissue constructs. Altogether, this research presents a suite of advanced therapeutic strategies that leverage cellular function across multiple length scales, offer remote controllability, and address crucial limitations in current transplantation and tissue engineering practices. These innovations hold significant promise for reducing the global impact of organ shortages. |
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