The design of multifunctional polymeric materials that combine structural, biological, and responsive properties remains a central challenge in the development of advanced platforms for biomedical applications. In this Thesis, different material design strategies were explored to engineer polymer-based systems with enhanced functionality, focusing on the integration of bioactive polyphenols, nanomaterials, and tailored surface modifications. The work spans applications in wound dressing, surface-functionalized scaffolds, cardiovascular biomaterials, MRI-visible vascular grafts, and 3D in vitro models for bone healing. In the first part of this work, polyphenol-based materials were introduced to develop a multifunctional wound dressing platform. Copper phosphate–tannic acid nanoflowers were synthesized through a green approach and incorporated into electrospun gum arabic/poly(vinyl alcohol) fibers coated with poly(caprolactone). The resulting scaffold exhibited reactive oxygen species scavenging activity, together with antibacterial and antibiofilm effects against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, while maintaining good hemocompatibility and biocompatibility. The following chapters focused on the use of poly(caprolactone) (PCL) as a central platform for the development of multifunctional scaffolds. Despite its widespread use due to its biocompatibility and biodegradability, the intrinsic hydrophobicity and limited surface reactivity of PCL restrict its biological performance. To address these limitations, a polymer design-based strategy was developed using blends of linear PCL and functionalized star-shaped PCL, enabling the introduction of reactive surface groups without compromising bulk properties. This allowed covalent immobilization of lysozyme, resulting in antibacterial activity while maintaining cytocompatibility. Additional surface modification through a gelatin/tannic acid coating provided antioxidant and antibacterial properties, with pH-responsive release behavior supported by molecular dynamics simulations, highlighting the role of hydrogen-bond-driven interactions. Building on this platform, PCL-based electrospun scaffolds were further engineered for cardiovascular applications. A PCL/PGS/gelatin system modified with tannic acid and in situ synthesized gold nanoparticles was developed as a potential cardiac patch. The scaffold preserved its extracellular matrix-like fibrous morphology while exhibiting tunable mechanical properties and enhanced electrical conductivity. Tannic acid contributed to increased elasticity, whereas gold nanoparticles improved stiffness and conductivity, while all formulations maintained good cytocompatibility. The versatility of PCL was further demonstrated in the development of MRI-visible vascular grafts. Electrospun PCL/PGS scaffolds incorporating quercetin and iron oxide nanoparticles were designed to combine bioactivity with imaging capability. Quercetin provided anti-inflammatory functionality, while iron oxide nanoparticles enabled non-invasive monitoring through MRI. The grafts exhibited strong T2*-weighted contrast, remained detectable under dynamic flow conditions, and preserved their structural integrity and cytocompatibility, demonstrating the potential of PCL-based systems as multifunctional and imageable vascular implants. The final part of the Thesis focused on the development of a 3D in vitro model for bone healing based on gelatin methacryloyl hydrogels. Rather than serving as a polymer scaffold for implantation, this system was designed as a controlled experimental platform to study defect bridging and healing behavior. The results revealed significant differences between mesenchymal stem cells and MC3T3-E1 preosteoblasts, with mesenchymal stem cells showing greater remodeling capacity. Complete closure was achieved only in 0.5 mm defects, highlighting the importance of biological context in the healing process and demonstrating the usefulness of this model for studying bone healing mechanisms and screening biomaterials. This Thesis presents an approach to the design and engineering of multifunctional polymeric systems, with particular emphasis on poly(caprolactone) as a versatile and adaptable platform. By combining PCL with bioactive polyphenols, functional coatings, and nanomaterials, it was possible to develop scaffolds with enhanced antibacterial, antioxidant, conductive, and imaging properties. In parallel, the development of a 3D in vitro bone healing model expands the scope of the work toward experimental platforms for investigating regenerative processes. Together, these findings highlight how material design and functionalization strategies can be used to create advanced polymer-based systems for a wide range of biomedical applications.
Design and Engineering of Multifunctional Polymeric Platforms for Biomedical Applications
AHMADPOOR, FATEMEH
2026-07-13
Abstract
The design of multifunctional polymeric materials that combine structural, biological, and responsive properties remains a central challenge in the development of advanced platforms for biomedical applications. In this Thesis, different material design strategies were explored to engineer polymer-based systems with enhanced functionality, focusing on the integration of bioactive polyphenols, nanomaterials, and tailored surface modifications. The work spans applications in wound dressing, surface-functionalized scaffolds, cardiovascular biomaterials, MRI-visible vascular grafts, and 3D in vitro models for bone healing. In the first part of this work, polyphenol-based materials were introduced to develop a multifunctional wound dressing platform. Copper phosphate–tannic acid nanoflowers were synthesized through a green approach and incorporated into electrospun gum arabic/poly(vinyl alcohol) fibers coated with poly(caprolactone). The resulting scaffold exhibited reactive oxygen species scavenging activity, together with antibacterial and antibiofilm effects against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, while maintaining good hemocompatibility and biocompatibility. The following chapters focused on the use of poly(caprolactone) (PCL) as a central platform for the development of multifunctional scaffolds. Despite its widespread use due to its biocompatibility and biodegradability, the intrinsic hydrophobicity and limited surface reactivity of PCL restrict its biological performance. To address these limitations, a polymer design-based strategy was developed using blends of linear PCL and functionalized star-shaped PCL, enabling the introduction of reactive surface groups without compromising bulk properties. This allowed covalent immobilization of lysozyme, resulting in antibacterial activity while maintaining cytocompatibility. Additional surface modification through a gelatin/tannic acid coating provided antioxidant and antibacterial properties, with pH-responsive release behavior supported by molecular dynamics simulations, highlighting the role of hydrogen-bond-driven interactions. Building on this platform, PCL-based electrospun scaffolds were further engineered for cardiovascular applications. A PCL/PGS/gelatin system modified with tannic acid and in situ synthesized gold nanoparticles was developed as a potential cardiac patch. The scaffold preserved its extracellular matrix-like fibrous morphology while exhibiting tunable mechanical properties and enhanced electrical conductivity. Tannic acid contributed to increased elasticity, whereas gold nanoparticles improved stiffness and conductivity, while all formulations maintained good cytocompatibility. The versatility of PCL was further demonstrated in the development of MRI-visible vascular grafts. Electrospun PCL/PGS scaffolds incorporating quercetin and iron oxide nanoparticles were designed to combine bioactivity with imaging capability. Quercetin provided anti-inflammatory functionality, while iron oxide nanoparticles enabled non-invasive monitoring through MRI. The grafts exhibited strong T2*-weighted contrast, remained detectable under dynamic flow conditions, and preserved their structural integrity and cytocompatibility, demonstrating the potential of PCL-based systems as multifunctional and imageable vascular implants. The final part of the Thesis focused on the development of a 3D in vitro model for bone healing based on gelatin methacryloyl hydrogels. Rather than serving as a polymer scaffold for implantation, this system was designed as a controlled experimental platform to study defect bridging and healing behavior. The results revealed significant differences between mesenchymal stem cells and MC3T3-E1 preosteoblasts, with mesenchymal stem cells showing greater remodeling capacity. Complete closure was achieved only in 0.5 mm defects, highlighting the importance of biological context in the healing process and demonstrating the usefulness of this model for studying bone healing mechanisms and screening biomaterials. This Thesis presents an approach to the design and engineering of multifunctional polymeric systems, with particular emphasis on poly(caprolactone) as a versatile and adaptable platform. By combining PCL with bioactive polyphenols, functional coatings, and nanomaterials, it was possible to develop scaffolds with enhanced antibacterial, antioxidant, conductive, and imaging properties. In parallel, the development of a 3D in vitro bone healing model expands the scope of the work toward experimental platforms for investigating regenerative processes. Together, these findings highlight how material design and functionalization strategies can be used to create advanced polymer-based systems for a wide range of biomedical applications.
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