RT info:eu-repo/semantics/doctoralThesis
T1 Development of novel wound dressing based on elastin-like recombinamers for skin regeneration
A1 Juanes Gusano, Diana
A2 Universidad de Valladolid. Escuela de Doctorado
K1 Ingeniería química
K1 Elastin like recombinamer
K1 Recombinámeros similares elast
K1 Materials
K1 Materiales
K1 Biomedicine
K1 Biomedicina
K1 Tissue engeeniering
K1 Ingeniería tisular
K1 32 Ciencias Médicas
AB Tissue engineering is an interdisciplinary field that combines engineering, biology, and medicine to develop innovative solutions for repairing, replacing, or enhancing tissues and organs in the human body. Success in this field depends on developing biomaterials that are biocompatible and functional, effectively interacting with target tissue cells and promoting their regeneration. These biomaterials include three-dimensional scaffolds, biodegradable matrices, and bioactive products that mimic the properties of natural tissues, providing a favorable environment for cell growth and differentiation. Additionally, developing biomaterials specific to different tissue types and clinical applications allows for more effective and personalized treatments, improving patients' quality of life and accelerating their recovery.Treating chronic wounds presents a significant challenge in healthcare, as these wounds can persist for long periods, affecting patients' quality of life and generating high treatment costs. In response, research has focused on developing biomaterials that facilitate and accelerate the healing process of chronic wounds. Biomaterials for wound dressings must provide an appropriate environment for tissue regeneration, promoting cell migration, proliferation, and extracellular matrix synthesis. These materials must meet several requirements, including offering a temporary protective barrier against external agents, being easy to apply, maintaining the correct moisture level, absorbing exudate, demonstrating good bioadhesion, elasticity, mechanical strength, ease of sterilization, and biodegradability without toxic or antigenic residues. Recombinant proteins are emerging as promising alternatives in regenerative medicine due to their ability to be genetically engineered, allowing precise control over their physicochemical and bioactive characteristics.Elastin-like recombinamers (ELRs) are the focus of this thesis. They are based on the pentapeptide repeat Val-Pro-Gly-X-Gly, found in natural elastin. The X residue can be any amino acid except L-proline, allowing the modulation of ELRs' physicochemical properties. If the residue contains functional groups, it can be used for further chemical modifications, such as covalently cross-linked hydrogels. The sequence of hydrophobic domains gives ELRs a smart thermo-responsive behavior in aqueous media, defined by the inverse temperature transition (ITT), allowing the economical purification of these materials through heating and cooling cycles, known as the inverse transition cycle (ITC).This thesis aims to develop new wound dressings for healing wounds using elastin-based scaffolds, such as membranes or hydrogels, incorporating enhanced bioactivities to meet all the requirements of an ideal dressing for skin regeneration. Detailed physicochemical and biological characterization of ELR membranes will be conducted to determine their suitability as dressings for hard-to-heal wounds. Additionally, developing multifunctional elastin-based hydrogels with high selectivity and bioactivity by including laminin sequences that significantly improve keratinocyte adhesion is proposed, benefiting wound healing.The thesis evaluates the physicochemical properties of ELR membranes, such as surface roughness, wettability, and degradation, crucial for their function and adhesion to the wound, and their influence on cell behavior. The biocompatibility and non-cytotoxicity of the membranes are analyzed using various methods to determine their suitability for tissue engineering applications. The regenerative capacity of these membranes is evaluated with an ex vivo human skin model, demonstrating good re-epithelialization without shrinkage. In vivo studies show that ELR membranes remain stable for at least seven weeks without rejection or foreign body effects, demonstrating their potential in wound regeneration by promoting self-regeneration of the surrounding tissue without the need for stem cells or external growth factors.
YR 2024
FD 2024
LK https://uvadoc.uva.es/handle/10324/71600
UL https://uvadoc.uva.es/handle/10324/71600
LA eng
NO Escuela de Doctorado
DS UVaDOC
RD 23-nov-2024