{"id":9691,"date":"2026-04-08T11:16:25","date_gmt":"2026-04-08T11:16:25","guid":{"rendered":"https:\/\/www.proefschriftmaken.nl\/portfolio\/nicole-van-gestel\/"},"modified":"2026-04-23T07:59:49","modified_gmt":"2026-04-23T07:59:49","slug":"nicole-van-gestel","status":"publish","type":"us_portfolio","link":"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/nicole-van-gestel\/","title":{"rendered":"Nicole Van Gestel"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"","protected":false},"author":8,"featured_media":13144,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"us_portfolio_category":[45],"class_list":["post-9691","us_portfolio","type-us_portfolio","status-publish","has-post-thumbnail","hentry","us_portfolio_category-new-template"],"acf":{"naam_van_het_proefschift":"Bioactive glass as bone graft substitute","samenvatting":"Er is geen Nederlandse samenvatting beschikbaar. De Engelse samenvatting vind je <a href=\"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/nicole-van-gestel\/\">hier<\/a>.","summary":"Bioactive glass as bone graft substitute\nIn vitro assessment of the mechanical and biological properties\n\nBioactive glass (BAG) was invented in the early \u201970s and was observed to bond to bone rather than being encapsulated by the human tissue. Since then, many different compositions have been developed. One of them is the SSPP4 composition, which is not only to be able to bond to bone, but it also has shown antibacterial properties against clinically relevant bacteria (this topic is further introduced in Chapter 1). Granules of the SSPP4 composition have been used in the clinic to treat bone infections (osteomyelitis) and good results have been achieved with a one-stage procedure. The conventional treatment for osteomyelitis is a two-stage method, using antibiotic-loaded-beads. In a first surgery, a cortical window is created and all the dead and infected bone is removed (debridement). The large cavity that remains is then filled with the antibiotic-loaded-beads. These beads need to be removed and replaced by a bone graft in a second surgery. With the use of SSPP4 BAG granules, the osteomyelitis treatment can be reduced to one surgery since the material can treat the infection and simultaneously graft the bone. The material has shown good clinical results in osteomyelitis (and in other clinical indications, as reviewed in Chapter 2). While the material was successfully used in the clinic, new questions arose about the use of the material in load-bearing defects. This started with a clinical case, where one unexpected fracture was observed a few days after the implantation of BAG granules. It remained unclear if the fracture could be related to the implanted material. In addition, surgeons identified suboptimal handling properties of the material, as they would prefer an injectable material over loose granules. Therefore new SSPP4 BAG formulations have been developed. These were the main reasons to start the research described in this thesis.\n\nAs a first goal, we aimed at a better understanding and predicting the load-bearing capacity of SSPP4 BAG granules. Osteomyelitis is a disease that often occurs in load-bearing bones and for the treatment the surgeon needs to create a large defect, which will weaken the whole bone. It has been shown that BAG granules can withstand high compressive forces without subsiding into bone in confined compression. We hypothesized that BAG granules should be able to contribute to load-bearing in confined defects. In Chapter 3, we created and defined a microfinite element model to describe the decrease in estimated failure moment and bone bending stiffness due to the defect. This showed the relation between the geometry of the defect and the decrease in stiffness and failure moment. In addition, the load sharing of BAG and bone morsels\/BAG mixtures in a more realistic clinical case was studied. A pragmatic modeling approach was used and showed a partially restored stiffness with the virtual implantation of either BAG granules alone or in a 50-50 vol% mixture with bone morsels. Moreover, it was observed that the granules carried about 25% of the applied load in simulated compression with optimal load-transfer conditions. These results indicate that the mixtures can contribute to the load-bearing in bones that are weakened due to a large defect with cortical window.\n\nAs a second goal, we aimed at defining how the incorporation of a synthetic binder, to create an injectable and moldable BAG putty, would affect the mechanical properties of the material. Chapter 4 describes evaluated compressive mechanical properties of five formulations with increasing binder content in a confined compression setup. The results showed that for load-bearing applications a putty with a low binder content and consequently high granule content would be beneficial over a putty with a high binder content. The results described in Chapter 4 were only obtained for dry samples, not taking into account the dissolution of the water soluble binder. This was determined in vitro in Chapter 5. Micro computed tomography revealed that the binder was dissolved within 12 hours, which would lead to a large unfilled volume (depending on the binder content used). This confirmed the conclusion of Chapter 4 that a material with a very low binder content could only be used in load-bearing cases. Also in the treatment of osteomyelitis, a fast dissolution of a high binder content may be detrimental, as the success rate of the treatment with BAG has been described to be dependent on the degree of filling. Just like an improper debridement, an improper filling could lead to reinfections.\n\nA fast dissolution of the binder would leave loose granules. In Chapter 5 we therefore also studied the degradation mechanisms of the glass itself. The granules have been reported to degrade very slowly in vivo, but it remained unclear what mechanisms could play a role. In Chapter 5 we observed that granules lost more weight and more ions in a solution with a pH of 4.6 compared to the physiological 7.4. Osteoclasts can also create such a low pH underneath their ruffled borders to degrade bone and were therefore hypothesized to be able to degrade BAG as well. The differentiation of human monocytes from blood (buffy coats) into osteoclasts was not impaired by the presence of ions from BAG when the cells were cultured on BAG surfaces for 18 days. Actively resorbing osteoclasts were observed with scanning electron microscopy after the culture period, but energy-dispersive X-ray spectroscopy suggested that the osteoclasts were not able to resorb the full material. The resorption pits observed on the BAG surface had a very smooth appearance compared to hydroxyapatite controls, which suggests that the cells were hindered by the silica in resorbing the complete material.\n\nThe results described in Chapter 5 were obtained with a relatively simple in vitro model, where a monoculture of cells cultured on BAG discs in the presence of differentiation medium. Although this shows that osteoclasts can play a role in the degradation of BAG in vitro, it remains unclear if that is also representative for the in vivo situation. It has been indicated that in vitro and in vivo results correlate poorly. It was hypothesized that this might be the result of the simplicity of the in vitro models compared to the complexity one would find in vivo, where more than only one cell type is present. Therefore the aim in Chapter 6 was to evaluate whether a novel approach could be used as a more complex test method to test for bone formation stimulated by (osteoinductive) biomaterials, in vitro. The approach entailed a culture platform for porcine osteochondral explants in which a critical sized bone defect was artificially created. Currently, no new bone formation was observed. The results in Chapter 6 provided clues on how to potentially enable new bone formation in the further experiments that are currently ongoing. When bone formation finally can be achieved, it will hold promise that this ex vivo 3D artificial grafting platform may be used to test the potential of newly developed biomaterials on their bone forming capacity, in the near future.\n\nApart from the mechanical properties (Chapter 4), it was also expected that the antibacterial properties would change with the incorporation of a synthetic binder to create the injectable putty material. This was also observed in Chapter 7 where the antibacterial properties of two putty formulations were tested against five different clinically relevant bacteria. The tested materials were not able to fully eradicate the tested pathogens in one week cultures. We also observed that previously obtained results with the SSPP4 glass granules could not be reproduced easily. We suggest that this also has to do with the granule sizes and correlated surface area, and the dose dependency of the ion release. This chapter underlines the importance of a better understanding of the antimicrobial mechanism of the SSPP4 material, in vitro.\n\nThe results obtained in this thesis are further discussed in Chapter 8. Overall, this thesis provides an overview of the load-bearing capacity of SSPP4 BAG granules and newly developed putty formulations. The loose granules can contribute to load-bearing in bones that are weakened by the creation of a cortical defect. The putty, in the current form, possesses mechanical properties and a degradation profile less suitable for load-bearing applications. The antibacterial properties of the newly developed putty formulations can also not be guaranteed yet. A better understanding of the antibacterial properties of the SSPP4 BAG in general is needed to enable new materials that can serve as antimicrobial bone graft substitutes based on BAGs. In addition, degradation of the SSPP4 granules has been studied and showed that osteoclasts can play a role in this degradation, in vitro. Whether this is representative for the in vivo situation remains to be studied. More complex 3D in vitro models may be used to study that in more detail and a first step of a new approach has been made.","auteur":"Nicole Van Gestel","auteur_slug":"nicole-van-gestel","publicatiedatum":"31 oktober 2019","taal":"EN","url_flipbook":"https:\/\/ebook.proefschriftmaken.nl\/ebook\/nicolevangestel?iframe=true","url_download_pdf":"","url_epub":"","ordernummer":"FTP-202604081113","isbn":"978-90-386-4870-5","doi_nummer":"","naam_universiteit":"TU Eindhoven","afbeeldingen":13144,"naam_student:":"","binnenwerk":"","universiteit":"TU Eindhoven","cover":"","afwerking":"","cover_afwerking":"","design":""},"_links":{"self":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/9691","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio"}],"about":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/types\/us_portfolio"}],"author":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/comments?post=9691"}],"version-history":[{"count":1,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/9691\/revisions"}],"predecessor-version":[{"id":9692,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/9691\/revisions\/9692"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media\/13144"}],"wp:attachment":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media?parent=9691"}],"wp:term":[{"taxonomy":"us_portfolio_category","embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio_category?post=9691"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}