{"id":{"repo_id":"tu-berlin","oai_identifier":"oai:depositonce.tu-berlin.de:11303/25039"},"canonical_url":"https://search.dev.ndltd.org/etd/tu-berlin/oai:depositonce.tu-berlin.de:11303/25039","repository":{"repo_id":"tu-berlin","name":"Technische Universität Berlin","base_url":"https://api-depositonce.tu-berlin.de/server/oai/request"},"display":{"title":"Metal-doped silicate microparticles for collagen scaffold-guided endochondral bone regeneration","abstract":"Endochondral ossification (EO) describes a process in which bone tissue builds up via a cartilaginous phase. In contrast to classical biomaterial approaches, which address bone regeneration via direct, intramembranous ossification (IO), a collagen scaffold was shown to stimulate endochondral healing of large bone defects. Here, its unique intrinsic bioactivity relied solely on its architecture without the need for progenitor cell seeding or the application of growth factors. To investigate how material components can have a bioactive contribution to the required cartilage formation during endochondral ossification (EO), this architecture-driven biomaterial approach was combined with the release of therapeutic metal ions. Silicate microparticles were chosen as a delivery platform for lithium, magnesium, strontium, or zinc ions, each of which is known to have a beneficial effect on cartilage and bone formation. An extensive in vitro evaluation, including the determination of the materials' physical properties as well as the bioactivity of ten fabricated hybrid scaffolds, was performed. An ion-specific cellular reaction was observed, wherein certain metal ions notably boosted the recruitment of cells into the material and displayed enhanced secretion of collagen II and chondrogenesis by human mesenchymal stromal cells (MSCs). Simultaneously, microparticle incorporation changed the mechanical characteristics of certain hybrid scaffolds, affecting cell-mediated material contraction and deformation of the scaffold walls. Endochondral bone formation, induced by the investigated collagen scaffold and during bone development, is a well-orchestrated differentiation process. Delivering anisotropic cellular cues in the form of biomolecular gradients plays an essential role, which results in the typical columnar, zonal organization of cells at different maturation stages. To recapitulate the structural aspects of the observed scaffold-guided tissue formation, a novel in vitro culture system was developed, which allows for EO-resembling spatiotemporal stimulation. Although certain limitations of the system were identified, the EO tissue polarization within collagen scaffold-MSCs constructs was successfully reproduced as observed previously in vivo. After cultivation, constructs displayed zones of chondrocytes, hypertrophic chondrocytes and matrix calcification. In summary, the results from evaluating different hybrid scaffolds indicated that the incorporation of metal-doped silicates has the potential to further increase the bioactivity of collagen scaffolds for endochondral bone regeneration. Secondly, an in vitro culture system was successfully developed that allows the recapitulation of EO in collagen scaffolds, serving as a valuable methodology for an advanced in vitro evaluation of future scaffold candidates.","abstract_html":"Endochondral ossification (EO) describes a process in which bone tissue builds up via a cartilaginous phase. In contrast to classical biomaterial approaches, which address bone regeneration via direct, intramembranous ossification (IO), a collagen scaffold was shown to stimulate endochondral healing of large bone defects. Here, its unique intrinsic bioactivity relied solely on its architecture without the need for progenitor cell seeding or the application of growth factors. To investigate how material components can have a bioactive contribution to the required cartilage formation during endochondral ossification (EO), this architecture-driven biomaterial approach was combined with the release of therapeutic metal ions. Silicate microparticles were chosen as a delivery platform for lithium, magnesium, strontium, or zinc ions, each of which is known to have a beneficial effect on cartilage and bone formation. An extensive in vitro evaluation, including the determination of the materials' physical properties as well as the bioactivity of ten fabricated hybrid scaffolds, was performed. An ion-specific cellular reaction was observed, wherein certain metal ions notably boosted the recruitment of cells into the material and displayed enhanced secretion of collagen II and chondrogenesis by human mesenchymal stromal cells (MSCs). Simultaneously, microparticle incorporation changed the mechanical characteristics of certain hybrid scaffolds, affecting cell-mediated material contraction and deformation of the scaffold walls. Endochondral bone formation, induced by the investigated collagen scaffold and during bone development, is a well-orchestrated differentiation process. Delivering anisotropic cellular cues in the form of biomolecular gradients plays an essential role, which results in the typical columnar, zonal organization of cells at different maturation stages. To recapitulate the structural aspects of the observed scaffold-guided tissue formation, a novel in vitro culture system was developed, which allows for EO-resembling spatiotemporal stimulation. Although certain limitations of the system were identified, the EO tissue polarization within collagen scaffold-MSCs constructs was successfully reproduced as observed previously in vivo. After cultivation, constructs displayed zones of chondrocytes, hypertrophic chondrocytes and matrix calcification. In summary, the results from evaluating different hybrid scaffolds indicated that the incorporation of metal-doped silicates has the potential to further increase the bioactivity of collagen scaffolds for endochondral bone regeneration. Secondly, an in vitro culture system was successfully developed that allows the recapitulation of EO in collagen scaffolds, serving as a valuable methodology for an advanced in vitro evaluation of future scaffold candidates.","abstract_has_math":false,"creators":["Stadter, Janina"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Kurreck, Jens"],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025","date_published":"2025","updated_at":"2026-07-27T21:28:54Z","subjects":[],"languages":["en"],"rights":[],"rights_urls":["https://creativecommons.org/licenses/by/4.0/"],"identifier_entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://doi.org/10.14279/depositonce-23856"],"render_values":[{"text":"https://doi.org/10.14279/depositonce-23856","href":"https://doi.org/10.14279/depositonce-23856","code":true}]}]},"links":{"outbound_url":"https://depositonce.tu-berlin.de/handle/11303/25039","outbound_label":"Repository record","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Kurreck, Jens"]},{"key":"dc:creator","label":"Author","values":["Stadter, Janina"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-11T14:40:45Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-11T14:40:45Z"]},{"key":"dc:date.issued","label":"Date","values":["2025"]},{"key":"dc:type","label":"Dc Type","values":["Doctoral Thesis"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights.uri","label":"Rights URI","values":["https://creativecommons.org/licenses/by/4.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://depositonce.tu-berlin.de/handle/11303/25039","https://doi.org/10.14279/depositonce-23856"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Endochondral ossification (EO) describes a process in which bone tissue builds up via a cartilaginous phase. In contrast to classical biomaterial approaches, which address bone regeneration via direct, intramembranous ossification (IO), a collagen scaffold was shown to stimulate endochondral healing of large bone defects. Here, its unique intrinsic bioactivity relied solely on its architecture without the need for progenitor cell seeding or the application of growth factors. To investigate how material components can have a bioactive contribution to the required cartilage formation during endochondral ossification (EO), this architecture-driven biomaterial approach was combined with the release of therapeutic metal ions. Silicate microparticles were chosen as a delivery platform for lithium, magnesium, strontium, or zinc ions, each of which is known to have a beneficial effect on cartilage and bone formation. An extensive in vitro evaluation, including the determination of the materials' physical properties as well as the bioactivity of ten fabricated hybrid scaffolds, was performed. An ion-specific cellular reaction was observed, wherein certain metal ions notably boosted the recruitment of cells into the material and displayed enhanced secretion of collagen II and chondrogenesis by human mesenchymal stromal cells (MSCs). Simultaneously, microparticle incorporation changed the mechanical characteristics of certain hybrid scaffolds, affecting cell-mediated material contraction and deformation of the scaffold walls. Endochondral bone formation, induced by the investigated collagen scaffold and during bone development, is a well-orchestrated differentiation process. Delivering anisotropic cellular cues in the form of biomolecular gradients plays an essential role, which results in the typical columnar, zonal organization of cells at different maturation stages. To recapitulate the structural aspects of the observed scaffold-guided tissue formation, a novel in vitro culture system was developed, which allows for EO-resembling spatiotemporal stimulation. Although certain limitations of the system were identified, the EO tissue polarization within collagen scaffold-MSCs constructs was successfully reproduced as observed previously in vivo. After cultivation, constructs displayed zones of chondrocytes, hypertrophic chondrocytes and matrix calcification. In summary, the results from evaluating different hybrid scaffolds indicated that the incorporation of metal-doped silicates has the potential to further increase the bioactivity of collagen scaffolds for endochondral bone regeneration. Secondly, an in vitro culture system was successfully developed that allows the recapitulation of EO in collagen scaffolds, serving as a valuable methodology for an advanced in vitro evaluation of future scaffold candidates.","Die endochondrale Ossifikation (EO) beschreibt einen Prozess, bei dem sich das Knochengewebe über eine knorpelige Phase aufbaut. Im Gegensatz zu klassischen Biomaterialansätzen, die die Knochenregeneration über eine direkte intramembranöse Ossifikation (IO) stimulieren, wurde gezeigt, dass ein Kollagengerüst die endochondrale Heilung großer Knochendefekte auslöst. Dabei beruhte seine einzigartige intrinsische Bioaktivität allein auf seiner Materialarchitektur, ohne dass ein Einbringen von Vorläuferzellen oder eine Anwendung von Wachstumsfaktoren erforderlich war. Um zu untersuchen, wie Materialkomponenten einen bioaktiven Beitrag zur notwendigen Knorpelbildung leisten können, wurde dieser architekturgesteuerte Biomaterialansatz mit der Freisetzung von therapeutischen Metallionen kombiniert. Silikat-Mikropartikel wurden als Plattform für die Freisetzung von Lithium-, Magnesium-, Strontium- oder Zink-Ionen ausgewählt, von denen bekannt ist, dass sie sich positiv auf die Knorpel- und Knochenbildung auswirken. Es wurde eine umfassende In-vitro-Bewertung durchgeführt, bei der die physikalischen Eigenschaften, sowie die Bioaktivität der zehn hergestellten Hybridmaterialien untersucht wurde. Hier zeigte sich eine ionenspezifische zelluläre Reaktion, bei der bestimmte Metallionen die Rekrutierung von Zellen in das Material deutlich verstärkten und eine erhöhte Sekretion von Kollagen II, sowie Chondrogenese durch humane mesenchymale Stromazellen (MSCs) aufwiesen. Gleichzeitig veränderte das Einbringen von Mikropartikeln die mechanischen Eigenschaften einiger Hybridmaterialien und beeinflusste die zellvermittelte Materialkontraktion, sowie die Verformung der Gerüstwände. Die endochondrale Knochenbildung, die im beschriebenen Kollagengerüst, aber auch während der Knochenentwicklung zu sehen ist, ist ein gut orchestrierter Differenzierungsprozess. Hierbei führen anisotrope, zelluläre Signale in Form biomolekularer Gradienten zur säulenförmigen Anordnung von Zellen in verschiedenen Reifungsstadien in bestimmten Zonen. Um die strukturellen Aspekte dieser beobachteten gerüstgesteuerten Gewebebildung nachzubilden, wurde ein neuartiges In-vitro-Kultursystem entwickelt, das eine EO-ähnliche raum-zeitliche Stimulation erlaubt. Trotz gewisser Einschränkungen des Systems konnte die zuvor in vivo beobachtete EO-Gewebepolarisation in Kollagen-MSC-Konstrukten erfolgreich reproduziert werden. Nach der Kultivierung wiesen die Konstrukte Zonen mit Chondrozyten, hypertrophen Chondrozyten und Matrixverkalkung auf. Zusammenfassend deuten die Ergebnisse aus der Bewertung verschiedener Hybridgerüste darauf hin, dass die Einarbeitung von metalldotierten Silikaten das Potenzial hat, die Bioaktivität von Kollagengerüsten für die endochondrale Knochenregeneration weiter zu erhöhen. Des Weiteren wurde ein In-vitro-Kultursystem erfolgreich entwickelt, das die Nachbildung des EO Prozesses in Kollagengerüsten ermöglicht und als wertvolle Methodik für eine fortgeschrittene In-vitro-Evaluierung zukünftiger Gerüstkandidaten dient."]},{"key":"dc:title","label":"Title","values":["Metal-doped silicate microparticles for collagen scaffold-guided endochondral bone regeneration"]}]}],"canonical_facts":{"dc:contributor.advisor":["Kurreck, Jens"],"dc:creator":["Stadter, Janina"],"dc:date.accessioned":["2025-07-11T14:40:45Z"],"dc:date.available":["2025-07-11T14:40:45Z"],"dc:date.issued":["2025"],"dc:description.abstract":["Endochondral ossification (EO) describes a process in which bone tissue builds up via a cartilaginous phase. In contrast to classical biomaterial approaches, which address bone regeneration via direct, intramembranous ossification (IO), a collagen scaffold was shown to stimulate endochondral healing of large bone defects. Here, its unique intrinsic bioactivity relied solely on its architecture without the need for progenitor cell seeding or the application of growth factors. To investigate how material components can have a bioactive contribution to the required cartilage formation during endochondral ossification (EO), this architecture-driven biomaterial approach was combined with the release of therapeutic metal ions. Silicate microparticles were chosen as a delivery platform for lithium, magnesium, strontium, or zinc ions, each of which is known to have a beneficial effect on cartilage and bone formation. An extensive in vitro evaluation, including the determination of the materials' physical properties as well as the bioactivity of ten fabricated hybrid scaffolds, was performed. An ion-specific cellular reaction was observed, wherein certain metal ions notably boosted the recruitment of cells into the material and displayed enhanced secretion of collagen II and chondrogenesis by human mesenchymal stromal cells (MSCs). Simultaneously, microparticle incorporation changed the mechanical characteristics of certain hybrid scaffolds, affecting cell-mediated material contraction and deformation of the scaffold walls. Endochondral bone formation, induced by the investigated collagen scaffold and during bone development, is a well-orchestrated differentiation process. Delivering anisotropic cellular cues in the form of biomolecular gradients plays an essential role, which results in the typical columnar, zonal organization of cells at different maturation stages. To recapitulate the structural aspects of the observed scaffold-guided tissue formation, a novel in vitro culture system was developed, which allows for EO-resembling spatiotemporal stimulation. Although certain limitations of the system were identified, the EO tissue polarization within collagen scaffold-MSCs constructs was successfully reproduced as observed previously in vivo. After cultivation, constructs displayed zones of chondrocytes, hypertrophic chondrocytes and matrix calcification. In summary, the results from evaluating different hybrid scaffolds indicated that the incorporation of metal-doped silicates has the potential to further increase the bioactivity of collagen scaffolds for endochondral bone regeneration. Secondly, an in vitro culture system was successfully developed that allows the recapitulation of EO in collagen scaffolds, serving as a valuable methodology for an advanced in vitro evaluation of future scaffold candidates.","Die endochondrale Ossifikation (EO) beschreibt einen Prozess, bei dem sich das Knochengewebe über eine knorpelige Phase aufbaut. Im Gegensatz zu klassischen Biomaterialansätzen, die die Knochenregeneration über eine direkte intramembranöse Ossifikation (IO) stimulieren, wurde gezeigt, dass ein Kollagengerüst die endochondrale Heilung großer Knochendefekte auslöst. Dabei beruhte seine einzigartige intrinsische Bioaktivität allein auf seiner Materialarchitektur, ohne dass ein Einbringen von Vorläuferzellen oder eine Anwendung von Wachstumsfaktoren erforderlich war. Um zu untersuchen, wie Materialkomponenten einen bioaktiven Beitrag zur notwendigen Knorpelbildung leisten können, wurde dieser architekturgesteuerte Biomaterialansatz mit der Freisetzung von therapeutischen Metallionen kombiniert. Silikat-Mikropartikel wurden als Plattform für die Freisetzung von Lithium-, Magnesium-, Strontium- oder Zink-Ionen ausgewählt, von denen bekannt ist, dass sie sich positiv auf die Knorpel- und Knochenbildung auswirken. Es wurde eine umfassende In-vitro-Bewertung durchgeführt, bei der die physikalischen Eigenschaften, sowie die Bioaktivität der zehn hergestellten Hybridmaterialien untersucht wurde. Hier zeigte sich eine ionenspezifische zelluläre Reaktion, bei der bestimmte Metallionen die Rekrutierung von Zellen in das Material deutlich verstärkten und eine erhöhte Sekretion von Kollagen II, sowie Chondrogenese durch humane mesenchymale Stromazellen (MSCs) aufwiesen. Gleichzeitig veränderte das Einbringen von Mikropartikeln die mechanischen Eigenschaften einiger Hybridmaterialien und beeinflusste die zellvermittelte Materialkontraktion, sowie die Verformung der Gerüstwände. Die endochondrale Knochenbildung, die im beschriebenen Kollagengerüst, aber auch während der Knochenentwicklung zu sehen ist, ist ein gut orchestrierter Differenzierungsprozess. Hierbei führen anisotrope, zelluläre Signale in Form biomolekularer Gradienten zur säulenförmigen Anordnung von Zellen in verschiedenen Reifungsstadien in bestimmten Zonen. Um die strukturellen Aspekte dieser beobachteten gerüstgesteuerten Gewebebildung nachzubilden, wurde ein neuartiges In-vitro-Kultursystem entwickelt, das eine EO-ähnliche raum-zeitliche Stimulation erlaubt. Trotz gewisser Einschränkungen des Systems konnte die zuvor in vivo beobachtete EO-Gewebepolarisation in Kollagen-MSC-Konstrukten erfolgreich reproduziert werden. Nach der Kultivierung wiesen die Konstrukte Zonen mit Chondrozyten, hypertrophen Chondrozyten und Matrixverkalkung auf. Zusammenfassend deuten die Ergebnisse aus der Bewertung verschiedener Hybridgerüste darauf hin, dass die Einarbeitung von metalldotierten Silikaten das Potenzial hat, die Bioaktivität von Kollagengerüsten für die endochondrale Knochenregeneration weiter zu erhöhen. Des Weiteren wurde ein In-vitro-Kultursystem erfolgreich entwickelt, das die Nachbildung des EO Prozesses in Kollagengerüsten ermöglicht und als wertvolle Methodik für eine fortgeschrittene In-vitro-Evaluierung zukünftiger Gerüstkandidaten dient."],"dc:identifier.uri":["https://depositonce.tu-berlin.de/handle/11303/25039","https://doi.org/10.14279/depositonce-23856"],"dc:language.iso":["en"],"dc:rights.uri":["https://creativecommons.org/licenses/by/4.0/"],"dc:title":["Metal-doped silicate microparticles for collagen scaffold-guided endochondral bone regeneration"],"dc:type":["Doctoral Thesis"]},"updated_at":"2026-07-27T21:28:54Z"}