Diseases and injuries related to bone and cartilage severely affect the function of the musculoskeletal system. They affect the life quality of patients and make them unable to move. The... Show moreDiseases and injuries related to bone and cartilage severely affect the function of the musculoskeletal system. They affect the life quality of patients and make them unable to move. The peculiarities of bone and cartilage structures mean that the therapeutic and surgical treatments that have been developed till date have a lot of disadvantages and limitations. Consequently, the development of new strategies for administering drugs that favor localized delivery is very important to achieve increasingly better treatments.The design and preparation of platforms for this purpose is a constant challenge, and for this reason three types of matrices were designed and prepared in the thesis. The drugs encapsulated in these matrices were cefazolin sodium, betamethasone, dexamethasone sodium phosphate, and Etanercept (anti-TNF-α drug). We were able to show that our matrices modified the release of the incorporated molecules and the composition of the prepared materials played an important role in the kinetics of the release process. Physicochemical characterizations were carried out on all the materials, obtaining that in each case the morphology varied once modifications in the matrix composition had been introduced. Biological studies in vitro and in vivo showed the cytocompatibility of the materials and also the ability to help repair damaged cartilage. Show less
Kotronoulas, A.; Lomana, A.L.G. de; Karvelsson, S.T.; Heijink, M.; Stone, R.; Giera, M.; Rolfsson, O. 2021
The use of acellular fish skin grafts (FSG) for the treatment of burn wounds is becoming more common due to its beneficial wound healing properties. In our previous study we demonstarted that FSG... Show moreThe use of acellular fish skin grafts (FSG) for the treatment of burn wounds is becoming more common due to its beneficial wound healing properties. In our previous study we demonstarted that FSG is a scaffold biomaterial that is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) conjugated to phosphatidylcholines. Here we investigated whether EPA and DHA derived lipid mediators are influenced during the healing of burn wounds treated with FSG. Deep partial and full thickness burn wounds (DPT and FT, respectively) were created on Yorkshire pigs (n = 4). DPT were treated with either FSG or fetal bovine dermis while FT were treated either with FSG or cadaver skin initially and followed by a split thickness skin graft. Punch biopsies were collected on days 7, 14, 21, 28 and 60 and analyzed in respect of changes to approximately 45 derivatives of EPA, DHA, arachidonic acid (AA), and linoleic acid (LA) employing UPLC-MS/MS methodology. Nine EPA and DHA lipid mediators, principally mono-hydroxylated derivatives such as 18-HEPE and 17-HDHA, were significantly higher on day 7 in the DPT when treated with FSG. A similar but non-significant trend was observed for the FT. The results suggest that the use of FSG in burn wound treatment can alter the formation of EPA and DHA mono hydroxylated lipid mediators in comparison to other grafts of mammalian origin. The differences observed during the first seven days after treatment indicates that FSG affects the early stages of wound healing. Show less
This dissertation contains four works during my PhD. Different biomaterials have been designed based on coiled-coil peptides. These biomaterials have a range of applications, inclusing drug... Show moreThis dissertation contains four works during my PhD. Different biomaterials have been designed based on coiled-coil peptides. These biomaterials have a range of applications, inclusing drug delivery, cell sorting to cell-cell fusion. By knowledge-guideddesign and modification, coiled-coil induced membrane fusion systems are expected to achieve drug delivery in vivo. Finally, L-forms obtained by coiled-coil induced fusion of different strains are expected to be an ideal model for studying questions related to the origin of life and novel antibiotics. Show less
The clinical success rate of islet transplantation, namely independence from insulin injections, is limited by factors that lead to graft failure, including inflammation, acute ischemia, acute... Show moreThe clinical success rate of islet transplantation, namely independence from insulin injections, is limited by factors that lead to graft failure, including inflammation, acute ischemia, acute phase response, and insufficient vascularization. The ischemia and insufficient vascularization both lead to high levels of oxidative stress, which are further aggravated by islet encapsulation, inflammation, and undesirable cell-biomaterial interactions. To identify biomaterials that would not further increase damaging oxidative stress levels and that are also suitable for manufacturing a beta cell encapsulation device, we studied five clinically approved polymers for their effect on oxidative stress and islet (alpha and beta cell) function. We found that 300 poly(ethylene oxide terephthalate) 55/poly(butylene terephthalate) 45 (PEOT/PBT300) was more resistant to breakage and more elastic than other biomaterials, which is important for its immunoprotective function. In addition, it did not induce oxidative stress or reduce viability in the MIN6 beta cell line, and even promoted protective endogenous antioxidant expression over 7 days. Importantly, PEOT/PBT300 is one of the biomaterials we studied that did not interfere with insulin secretion in human islets. Show less
Vermeulen, S.; Roumans, N.; Honig, F.; Carlier, A.; Hebels, D.G.A.J.; Eren, A.D.; ... ; Boer, J. de 2020
We previously found that surface topographies induce the expression of the Scxa gene, encoding Scleraxis in tenocytes. Because Scxa is a TGF-beta responsive gene, we investigated the link between... Show moreWe previously found that surface topographies induce the expression of the Scxa gene, encoding Scleraxis in tenocytes. Because Scxa is a TGF-beta responsive gene, we investigated the link between mechanotransduction and TGF-beta signaling. We discovered that mesenchymal stem cells exposed to both micro-topographies and TGF-beta 2 display synergistic induction of SMAD phosphorylation and transcription of the TGF-beta target genes SCX, alpha-SMA, and SOX9. Pharmacological perturbations revealed that Rho/ROCK/SRF signaling is required for this synergistic response. We further found an activation of the early response genes SRF and EGR1 during the early adaptation phase on micro-topographies, which coincided with higher expression of the TGF-beta type II receptor gene. Of interest, PKC activators Prostratin and Ingenol-3, known for inducing actin reorganization and activation of serum response elements, were able to mimic the topography-induced TGF-beta response. These findings provide novel insights into the convergence of mechanobiology and TGF-beta signaling, which can lead to improved culture protocols and therapeutic applications. Show less
The aim of this thesis is to develop and study a robust and adaptable scaffold for supramolecular polymer self-assembly in water. For this purpose, I rely on the use of squaramides to provide... Show moreThe aim of this thesis is to develop and study a robust and adaptable scaffold for supramolecular polymer self-assembly in water. For this purpose, I rely on the use of squaramides to provide directional interactions in order to drive the formation of one-dimensional aggregates through self-assembly. The interplay of hydrogen-bonding and aromaticity in the monomer self-assembly process is explored in the squaramide unit, by examining the consequence of aromatic gain on this process. Additionally, by systematic modification of the monomer structure, a library of supramolecular structures with different morphologies is developed and their use as future drug nanovehicles is studied in an in vivo model involving zebrafish embryos. Show less
