Optimization of mimetic periosteum autografts for the treatment of nonunions

Bone presents truly regenerative capacity being able to regenerate into a native state in response to injuries. Despite this self-renewal potential, bone healing is not absent of complications and different conditions can interfere with the regenerative process, leading to delayed fracture and in so...

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Autor: Romero-Torrecilla, J.A. (Juan Antonio)|||/items/0d94fc20-5c0d-42aa-8da5-e162ef65978d
Tipo de recurso: tesis doctoral
Fecha de publicación:2023
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/68418
Acceso en línea:https://hdl.handle.net/10171/68418
Access Level:acceso abierto
Palabra clave:Materias Investigacion::Ciencias de la Salud::Reumatología
Nonunions
Mimetic periosteum autografts
Pseudoarthrosis
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spelling Optimization of mimetic periosteum autografts for the treatment of nonunionsRomero-Torrecilla, J.A. (Juan Antonio)|||/items/0d94fc20-5c0d-42aa-8da5-e162ef65978dMaterias Investigacion::Ciencias de la Salud::ReumatologíaNonunionsMimetic periosteum autograftsPseudoarthrosisBone presents truly regenerative capacity being able to regenerate into a native state in response to injuries. Despite this self-renewal potential, bone healing is not absent of complications and different conditions can interfere with the regenerative process, leading to delayed fracture and in some cases fracture nonunion. Fracture nonunion is a major cause of chronic pain and disability and, despite the low incidence of nonunion and delayed union fractures (5-10%), the numerous fractures that take place globally (~180 million every year) emphasizes the huge economic burden that fracture nonunion represents. Once detected, fracture nonunion requires a surgical approach, and the use of bone autografts that provide and osteoinductive, osteogenic and osteoconductive environment for a successful repair. However, the availability of bone grafts is limited. The scarcity of bone tissue that can be used for autografts have consolidated the need for novel tissue engineering approaches as potential candidates for the treatment of nonunion and for long bone defects, prone to evolve to nonunions. Tissue engineering strategies allow for the combination of novel tunable materials along with different biological adjuvants, including growth factors and cells. During the bone regenerative response, the periosteum, a fibrous layer surrounding the bone, plays a key role delivering osteochondroprogenitor cells and crucial growth factors into the injured tissue. Thus, we developed a tissue engineering strategy where biocompatible, 3D melt-electro-written polycaprolactone membrane would act as a mimetic periosteum. The engineered mimetic periosteum allows vascularization of the construct either when implanted ectopically or orthotopically. Additionally, we demonstrated its capacity to be functionalized with rhBMP-2, the most important morphogen for bone regeneration, both exposed on the membrane surface attached through PEA-hFN or encapsulated in microparticles covalently bound to the PCL membrane. When functionalized with low doses of rhBMP-2 the mimetic periosteum demonstrated great osteogenic potential in vitro, inducing human MSCs differentiation into osteoblasts. More importantly, in vivo results indicate that the functionalization of the mimetic periosteum with rhBMP-2 allows regenerative properties able to heal critical size femoral defects in SD rats with high efficiency and reproducibility using unpreceded low doses of rhBMP-2. Ultimately, the mimetic periosteum demonstrated its ability to deliver key mesenchymal progenitor cells into the injured site. All these results indicate that our engineered mimetic periosteum represents an efficient system for rhBMP-2 and progenitor cells delivery with important translational potential.Universidad de NavarraGranero-Moltó, F. (Froilán)Dadun. Depósito Académico Digital Universidad de Navarra20242024-01-1820242024-01-1820242024-01-1820232023-12-14doctoral thesishttp://purl.org/coar/resource_type/c_db06info:eu-repo/semantics/doctoralThesisapplication/pdfhttps://hdl.handle.net/10171/68418reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/684182026-06-21T12:47:57Z
dc.title.none.fl_str_mv Optimization of mimetic periosteum autografts for the treatment of nonunions
title Optimization of mimetic periosteum autografts for the treatment of nonunions
spellingShingle Optimization of mimetic periosteum autografts for the treatment of nonunions
Romero-Torrecilla, J.A. (Juan Antonio)|||/items/0d94fc20-5c0d-42aa-8da5-e162ef65978d
Materias Investigacion::Ciencias de la Salud::Reumatología
Nonunions
Mimetic periosteum autografts
Pseudoarthrosis
title_short Optimization of mimetic periosteum autografts for the treatment of nonunions
title_full Optimization of mimetic periosteum autografts for the treatment of nonunions
title_fullStr Optimization of mimetic periosteum autografts for the treatment of nonunions
title_full_unstemmed Optimization of mimetic periosteum autografts for the treatment of nonunions
title_sort Optimization of mimetic periosteum autografts for the treatment of nonunions
dc.creator.none.fl_str_mv Romero-Torrecilla, J.A. (Juan Antonio)|||/items/0d94fc20-5c0d-42aa-8da5-e162ef65978d
author Romero-Torrecilla, J.A. (Juan Antonio)|||/items/0d94fc20-5c0d-42aa-8da5-e162ef65978d
author_facet Romero-Torrecilla, J.A. (Juan Antonio)|||/items/0d94fc20-5c0d-42aa-8da5-e162ef65978d
author_role author
dc.contributor.none.fl_str_mv Granero-Moltó, F. (Froilán)
Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv Materias Investigacion::Ciencias de la Salud::Reumatología
Nonunions
Mimetic periosteum autografts
Pseudoarthrosis
topic Materias Investigacion::Ciencias de la Salud::Reumatología
Nonunions
Mimetic periosteum autografts
Pseudoarthrosis
description Bone presents truly regenerative capacity being able to regenerate into a native state in response to injuries. Despite this self-renewal potential, bone healing is not absent of complications and different conditions can interfere with the regenerative process, leading to delayed fracture and in some cases fracture nonunion. Fracture nonunion is a major cause of chronic pain and disability and, despite the low incidence of nonunion and delayed union fractures (5-10%), the numerous fractures that take place globally (~180 million every year) emphasizes the huge economic burden that fracture nonunion represents. Once detected, fracture nonunion requires a surgical approach, and the use of bone autografts that provide and osteoinductive, osteogenic and osteoconductive environment for a successful repair. However, the availability of bone grafts is limited. The scarcity of bone tissue that can be used for autografts have consolidated the need for novel tissue engineering approaches as potential candidates for the treatment of nonunion and for long bone defects, prone to evolve to nonunions. Tissue engineering strategies allow for the combination of novel tunable materials along with different biological adjuvants, including growth factors and cells. During the bone regenerative response, the periosteum, a fibrous layer surrounding the bone, plays a key role delivering osteochondroprogenitor cells and crucial growth factors into the injured tissue. Thus, we developed a tissue engineering strategy where biocompatible, 3D melt-electro-written polycaprolactone membrane would act as a mimetic periosteum. The engineered mimetic periosteum allows vascularization of the construct either when implanted ectopically or orthotopically. Additionally, we demonstrated its capacity to be functionalized with rhBMP-2, the most important morphogen for bone regeneration, both exposed on the membrane surface attached through PEA-hFN or encapsulated in microparticles covalently bound to the PCL membrane. When functionalized with low doses of rhBMP-2 the mimetic periosteum demonstrated great osteogenic potential in vitro, inducing human MSCs differentiation into osteoblasts. More importantly, in vivo results indicate that the functionalization of the mimetic periosteum with rhBMP-2 allows regenerative properties able to heal critical size femoral defects in SD rats with high efficiency and reproducibility using unpreceded low doses of rhBMP-2. Ultimately, the mimetic periosteum demonstrated its ability to deliver key mesenchymal progenitor cells into the injured site. All these results indicate that our engineered mimetic periosteum represents an efficient system for rhBMP-2 and progenitor cells delivery with important translational potential.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-12-14
2024
2024-01-18
2024
2024-01-18
2024
2024-01-18
dc.type.none.fl_str_mv doctoral thesis
http://purl.org/coar/resource_type/c_db06
dc.type.openaire.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/68418
url https://hdl.handle.net/10171/68418
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidad de Navarra
publisher.none.fl_str_mv Universidad de Navarra
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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