Publicação
Development of regenerative medicine therapies based on Platelet-Derived Products for the treatment approaches of dogs and cats
| Resumo: | Platelet-derived products (PDPs) are hemoderivatives that have gained popularity, mainly due to their high concentrations of bioactive molecules such as growth factors (GFs) and cytokines (IL), which play important roles in tissue healing and regeneration. Their therapeutic effect has been widely recognized in human medicine. The rationale for the use of platelet-based products stems from the fact that platelets, after being activated, release their associated structural proteins and others, that modulate inflammation and tissue repair. PDPs embraced in this thesis are envisioned as biodegradable, economic, safe, fast, and easily obtained in the clinics, for both tissue engineering and regenerative therapy strategies. In veterinary medicine, however, the lack of standard protocols to generate PDPs is a major hurdle for assessing the clinical relevance of PDP-based therapies, and their widespread usage. The most cited hemoderivatives applied in human and veterinary settings can be roughly classified into platelet-poor and platelet-rich products. They are distinguished mainly by the presence of platelets, not devaluing, however, their composition in leukocytes. The most cited and studied PDPs are i) the platelet concentrate (PC), which is sometimes referred to as platelet-rich plasma (PRP); ii) platelet-poor plasma (PPP); and iii) platelet-rich fibrin (PRF). All these fractions can be obtained from a simple blood collection. This thesis investigates specific hemoderivatives with therapeutic interest, in a real clinical veterinary context: the canine-sourced PRFs (as an active biomaterial for wound regeneration), and both canine and feline PCs (for other clinical treatment methodologies, in dogs and cats). Chapter I scrutinizes the technical and scientific specificities of PDPs in terms of preparation methodologies, classification categorization, nomenclature, and biological properties to advance their future biotechnological potential in veterinary contexts. Furthermore, this chapter also summarises the clinical cases reported in veterinary medicine using the PRDs, claiming the use of well-characterized platelet-based formulation in both laboratory and clinical veterinary contexts. Chapter II summarises the research objectives of this project. Chapter III aimed to characterize both canine and feline-origin PRFs. Moreover, a standardized protocol was obtained using low blood volume, and the structural and biochemical characterization of PRFs from dogs and cats was demonstrated. According to the authors' knowledge, this is the first work characterizing canine and feline PRFs in terms of secretome protein pattern and structure. Chapters IV, V, VI, and VII address the clinical efficacy of PRF-therapy as an innovative grafting technique for wound regeneration in dogs and cats, as an autologous, allogeneic, or xenogeneic methodology. This section represents clinical research in real patients (domestic dogs and cats), demonstrating the clinical performance of PRF-therapy in the treatment of naturally occurring skin wounds. PRF-therapy was considered an effective and safe biological regenerative therapy for wound regeneration, revealing a natural antimicrobial effect. Chapter VIII focuses on the production of canine PCs within the clinic, reporting a considerable donor variability associated with their manufacture, using the double centrifugation technique. This research feature has not been described in the literature on canine species. Additionally, Chapter IX describes the optimization of a standard protocol for feline-sourced PC manufacture, using a double centrifugation technique, also reproducible in the clinics, avoiding the use of commercial kits. Furthermore, the proposed protocol used low-volume blood samples, revealing a highly efficient protocol. Lastly, Chapter X comprises the General Discussion, and Chapter XI is the main Concluding Remarks of the work developed under the scope of this thesis. |
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| Autores principais: | Soares, Carla Sofia Alves |
| Assunto: | Platelet-therapy growth factors |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade de Trás-os-Montes e Alto Douro |
| Idioma: | inglês |
| Origem: | Repositório da UTAD |
| Resumo: | Platelet-derived products (PDPs) are hemoderivatives that have gained popularity, mainly due to their high concentrations of bioactive molecules such as growth factors (GFs) and cytokines (IL), which play important roles in tissue healing and regeneration. Their therapeutic effect has been widely recognized in human medicine. The rationale for the use of platelet-based products stems from the fact that platelets, after being activated, release their associated structural proteins and others, that modulate inflammation and tissue repair. PDPs embraced in this thesis are envisioned as biodegradable, economic, safe, fast, and easily obtained in the clinics, for both tissue engineering and regenerative therapy strategies. In veterinary medicine, however, the lack of standard protocols to generate PDPs is a major hurdle for assessing the clinical relevance of PDP-based therapies, and their widespread usage. The most cited hemoderivatives applied in human and veterinary settings can be roughly classified into platelet-poor and platelet-rich products. They are distinguished mainly by the presence of platelets, not devaluing, however, their composition in leukocytes. The most cited and studied PDPs are i) the platelet concentrate (PC), which is sometimes referred to as platelet-rich plasma (PRP); ii) platelet-poor plasma (PPP); and iii) platelet-rich fibrin (PRF). All these fractions can be obtained from a simple blood collection. This thesis investigates specific hemoderivatives with therapeutic interest, in a real clinical veterinary context: the canine-sourced PRFs (as an active biomaterial for wound regeneration), and both canine and feline PCs (for other clinical treatment methodologies, in dogs and cats). Chapter I scrutinizes the technical and scientific specificities of PDPs in terms of preparation methodologies, classification categorization, nomenclature, and biological properties to advance their future biotechnological potential in veterinary contexts. Furthermore, this chapter also summarises the clinical cases reported in veterinary medicine using the PRDs, claiming the use of well-characterized platelet-based formulation in both laboratory and clinical veterinary contexts. Chapter II summarises the research objectives of this project. Chapter III aimed to characterize both canine and feline-origin PRFs. Moreover, a standardized protocol was obtained using low blood volume, and the structural and biochemical characterization of PRFs from dogs and cats was demonstrated. According to the authors' knowledge, this is the first work characterizing canine and feline PRFs in terms of secretome protein pattern and structure. Chapters IV, V, VI, and VII address the clinical efficacy of PRF-therapy as an innovative grafting technique for wound regeneration in dogs and cats, as an autologous, allogeneic, or xenogeneic methodology. This section represents clinical research in real patients (domestic dogs and cats), demonstrating the clinical performance of PRF-therapy in the treatment of naturally occurring skin wounds. PRF-therapy was considered an effective and safe biological regenerative therapy for wound regeneration, revealing a natural antimicrobial effect. Chapter VIII focuses on the production of canine PCs within the clinic, reporting a considerable donor variability associated with their manufacture, using the double centrifugation technique. This research feature has not been described in the literature on canine species. Additionally, Chapter IX describes the optimization of a standard protocol for feline-sourced PC manufacture, using a double centrifugation technique, also reproducible in the clinics, avoiding the use of commercial kits. Furthermore, the proposed protocol used low-volume blood samples, revealing a highly efficient protocol. Lastly, Chapter X comprises the General Discussion, and Chapter XI is the main Concluding Remarks of the work developed under the scope of this thesis. |
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