| 1. |
- Ajalloueian, Fatemeh, et al.
(författare)
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A bedside collagen-PLGA nanofibrous construct for autologous transplantation of minced bladder mucosal
- 2012
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Ingår i: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254. ; 6:suppl 1, s. 128-128
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Bladder regeneration using minced bladder mucosa is an alternative to costly and time-consuming conventional in vitro culturing of urothelial cells. In this method, the uroepithelium expands in vivo and the patient body appears as an incubator. With our preliminary successes, designing an appropriate scaffold that supports in vivo cell expansion and surgical handling in a clinical setting was our aim. This study, investigates cell expansion in a hybrid construct of collagen/poly (lactic-co-glycolide)(PLGA).Materials and methods: An electrospun PLGA mat was placed on a semi-gel collagen inside a mold and covered with a second collagen layer. After gel formation, minced particles of pig bladder mucosa were seeded on the hybrid construct and then processed by plastic compression (PC). The scaffolds were incubated for 2, 4 and 6 weeks in vitro for further studies.Results: Tensile tests show an increase in tensile strength of 0.6 ± 0.1 MPa in PC collagen to 3.6 ± 1.1 MPa in hybrid construct. Morphological studies, histological staining and SEM show that the construct has kept its integrity during the time and proliferated urothelial cells have reached confluence after 4 weeks and a multi-layered urothelium after 6 weeks.Conclusion: We have designed a mechanically robust scaffold that permits surgical handling and tissue expansion in vivo. The construct is easy-to-use for clinical application in an ordinary surgical operating theater for bladder regeneration.
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| 2. |
- Ajalloueian, Fatemeh, et al.
(författare)
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Bladder biomechanics and the use of scaffolds for regenerative medicine in the urinary bladder
- 2018
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Ingår i: Nature reviews. Urology. - : Springer Science and Business Media LLC. - 1759-4812 .- 1759-4820. ; 15:3, s. 155-174
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Forskningsöversikt (refereegranskat)abstract
- The urinary bladder is a complex organ with the primary functions of storing urine under low and stable pressure and micturition. Many clinical conditions can cause poor bladder compliance, reduced capacity, and incontinence, requiring bladder augmentation or use of regenerative techniques and scaffolds. To replicate an organ that is under frequent mechanical loading and unloading, special attention towards fulfilling its biomechanical requirements is necessary. Several biological and synthetic scaffolds are available, with various characteristics that qualify them for use in bladder regeneration in vitro and in vivo, including in the treatment of clinical conditions. The biomechanical properties of the native bladder can be investigated using a range of mechanical tests for standardized assessments, as well as mathematical and computational bladder biomechanics. Despite a large body of research into tissue engineering of the bladder wall, some features of the native bladder and the scaffolds used to mimic it need further elucidation. Collection of comparable reference data from different animal models would be a helpful tool for researchers and will enable comparison of different scaffolds in order to optimize characteristics before entering preclinical and clinical trials.
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| 3. |
- Badali, Elham, et al.
(författare)
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Enzymatic Crosslinked Hydrogels for Biomedical Application
- 2021
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Ingår i: Polymer science. - : Springer. - 0965-545X. ; 63:SUPPL 1, s. S1-S22
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Forskningsöversikt (refereegranskat)abstract
- Self-assembled structures primarily arise through enzyme-regulated phenomena in nature under persistent conditions. Enzymatic reactions are one of the main biological processes constructing supramolecular hydrogel networks required for biomedical applications. Such enzymatic processes provide a unique opportunity to integrate hydrogel formation. In most cases, the structure and substrates of hydrogels are adjusted by enzyme catalysis due to enzymes' chemo-, regio- and stereo-selectivity. Such hydrogels processed using various enzyme schemes showed remarkable characteristics as dynamic frames for cells, bioactive molecules, and drugs in tissue engineering, drug delivery, and regenerative medicine. The enzyme-mediated crosslinking hydrogels mimic the extracellular matrices by displaying unique physicochemical properties and functionalities such as water-retention capacity, biodegradability, biocompatibility, biostability, bioactivity, optoelectronic properties, self-healing ability, and shape memory ability. In recent years, many enzymatic systems investigated polymer crosslinking. Herein, we review efficient strategies for enzymatic hydrogelation, including hydrogel synthesis and chemistry, and demonstrate their applicability in biomedical systems. Furthermore, the advantages, challenges, and prospects of enzymatic-crosslinkable hydrogels are discussed. The results of biocompatible hydrogel products show that these crosslinking mechanisms can fulfill requirements for a variety of biomedical applications, including tissue engineering, wound healing, and drug delivery.
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| 4. |
- Bermejo, Daniel, 1985-, et al.
(författare)
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First Aldol-Crosslinked Hyaluronic Acid Hydrogel: Fast and Hydrolytically Stable Gel with Tissue Adhesive Properties
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Ingår i: Chemical Sciences Journal. - 2150-3494.
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Tidskriftsartikel (refereegranskat)abstract
- Currently, there are limited approaches to tailor 3D scaffolds crosslinked with a stable covalent C-C bond that does not require any catalysts or initiators. We present here the first hydrogels employing aldol condensation chemistry that exhibit exceptional physicochemical properties. We investigated the aldol-crosslinking chemistry using two types of aldehyde-modified hyaluronic acid (HA) derivatives, namely; an enolizable HA-aldehyde (HA-Eal) and a non-enolizable HA-aldehyde (HA-Nal). Hydrogels formed using HA-Eal demonstrate inferior crosslinking efficiency (due to intramolecular loop formation), when compared with hydrogels formed by mixing HA-Eal and HA-NaI leading to a cross-aldol product. The change in mechanical properties as a result of crosslinking at different pH is determined using rheological measurements and is interpreted in terms of molecular weight between cross-links (Mc). The novel HA cross-aldol hydrogels demonstrate excellent hydrolytic stability and favorable mechanical properties but allow hyaluronidase mediated enzymatic degradation. Interestingly, residual aldehyde functionality within the aldol product leads to adhesion to tissue as demonstrated by bonding two bone tissues. The aldehyde functionality also permits facile post-synthetic modifications with nucleophilic reagents such as Alexa FluorTM 488. Finally, we demonstrate that the novel hydrogel is biocompatible with encapsulated stem cells that show a linear rate of expansion in our 3–6 days of study.
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| 5. |
- Bermejo-Velasco, Daniel, 1985-, et al.
(författare)
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First Aldol Cross-Linked Hyaluronic Acid Hydrogel : Fast and Hydrolytically Stable Hydrogel with Tissue Adhesive Properties
- 2019
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 11:41, s. 38232-38239
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Tidskriftsartikel (refereegranskat)abstract
- Currently, there are limited approaches to tailor 3D scaffolds cross-linked with a stable covalent C-C bond that does not require any catalysts or initiators. We present here the first hydrogels employing aldol condensation chemistry that exhibit exceptional physicochemical properties. We investigated the aldol-cross-linking chemistry using two types of aldehyde-modified hyaluronic acid (HA) derivatives, namely, an enolizable HA-aldehyde (HA-EaI) and a non-enolizable HA-aldehyde (HA-NaI). Hydrogels formed using HA-EaI demonstrate inferior cross linking efficiency (due to intramolecular loop formation), when compared with hydrogels formed by mixing HA-EaI and HA-NaI leading to a cross-aldol product. The change in mechanical properties as a result of cross-linking at different pH values is determined using rheological measurements and is interpreted in terms of molecular weight between cross-links (Me). The novel HA cross-aldol hydrogel demonstrate excellent hydrolytic stability and favorable mechanical properties but allow hyaluronidase-mediated enzymatic degradation. Interestingly, residual aldehyde functionality within the aldol product rendered the tissue adhesive properties by bonding two bone tissues. The aldehyde functionality also facilitated facile post-synthetic modifications with nucleophilic reagents. Finally, we demonstrate that the novel hydrogel is biocompatible with encapsulated stem cells that show a linear rate of expansion in our 3-6 days of study.
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| 6. |
- Bermejo-Velasco, Daniel, 1985-, et al.
(författare)
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Injectable hyaluronic acid hydrogels with the capacity for magnetic resonance imaging
- 2018
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Ingår i: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 197, s. 641-648
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Tidskriftsartikel (refereegranskat)abstract
- Monitoring hydrogel degradation in real time using noninvasive imaging techniques is of great interest for designing a scaffold in tissue engineering. We report the preparation of gadolinium (Gd)-labeled and injectable hyaluronic acid (HA) hydrogels that can be visualized using T-1- and T-2-weighted magnetic resonance imaging (MRI). An HA derivative functionalized with thiol and hydrazide was labeled using a diethylenetriaminepentaacetate complex modified with "clickable" dithiopyridyl functionalities (degree of modification was 3.77% with respect to HA repeat units). The HA derivative modified with cross-linkable groups and Gd complex exhibited relaxivities r(1) = 3.78 mM(-1)s(-1) and r(2) = 56.3 mM(-1)s(-1). A hydrazone hydrogel network was obtained by mixing Gd-labeled HA-hydrazide and HA-aldehyde derivatives. Enzymatic hydrogel degradation could be followed using MRI because the MR images showed great correlation with the hydrogel mass loss. Ex vivo MRI of injected Gd-labeled hydrogels demonstrated that they show a significant contrast difference (SNRcoronal = 456; SNRaxial = 459) from the surrounding tissues. These results indicate that our Gd-labeled HA hydrogel has great potential as an injectable biocompatible hydrogel that can be used for longitudinal tracking in vivo using MRI.
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| 7. |
- Bermejo-Velasco, Daniel, 1985-
(författare)
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Insights into Covalent Chemistry for the Development of Biomaterials
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Covalent cross-linking chemistry is currently exploited in the preparation of biomaterial for biomedical applications. Choice of these chemistries for the preparation of biomaterials and bioconjugates strongly influences the biological output of these materials. Therefore, this thesis aims to develop novel bioconjugation strategies understanding their advantages and drawbacks. Our results provide new insight to adapt these chemical transformations for a specific application.The first part of this thesis points out the relevance of tuning different properties of biomaterials with specific emphasis on the development of hyaluronic acid (HA) hydrogels. The second part of the thesis describes how different chemical transformations including hydrazone formation (Paper I), thiazolidine formation (Paper II), cross-aldol addition reaction (Paper III) and disulfide formation (Paper IV) dictate material properties.This thesis explores both basic organic reaction mechanism and application of these reactions to influence material characteristics. The detailed study of the reaction conditions, kinetics, and stability of the products will help to understand the mechanical properties, hydrolytic stability, and degradability of the materials described here.Additionally, we performed degradation studies of gadolinium labeled HA hydrogels using magnetic resonance imaging. Furthermore, we also explored post-synthetic modification of hydrogels to link model fluorescent moieties as well as explored the tissue adhesive properties using Schiff-base formation.In summary, this thesis presents a selection of different covalent chemistries for the design of advanced biomaterials. The advantages and disadvantages of these chemistries are rigorously investigated. We believe, such an investigation provides a better understanding of the bioconjugation strategies for the preparation of biomaterials with potential clinical translation.
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| 8. |
- Bermejo-Velasco, Daniel, 1985-, et al.
(författare)
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Modulating thiol pKa promotes disulfide formation at physiological pH : An elegant strategy to design disulfide cross-linked hyaluronic acid hydrogels
- 2019
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 20:3, s. 1412-1420
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Tidskriftsartikel (refereegranskat)abstract
- The disulfide bond plays a crucial role in protein biology and has been exploited by scientists to develop antibody-drug conjugates, sensors and for the immobilization other biomolecules to materials surfaces. In spite of its versatile use, the disulfide chemistry suffers from some inevitable limitations such as the need for basic conditions (pH > 8.5), strong oxidants and long reaction times. We demonstrate here that thiol-substrates containing electron-withdrawing groups at the β-position influence the deprotonation of the thiol group, which is the key reaction intermediate in the formation of disulfide bonds. Evaluation of reaction kinetics using small molecule substrate such as L-cysteine indicated disulfide formation at a 2.8-fold higher (k1 = 5.04 x 10-4 min-1) reaction rate as compared to the conventional thiol substrate, namely 3-mercaptopropionic acid (k1 = 1.80 x 10-4 min-1) at physiological pH (pH 7.4). Interestingly, the same effect could not be observed when N-acetyl-L-cysteine substrate (k1 = 0.51 x 10-4 min-1) was used. We further grafted such thiol-containing molecules (cysteine, N-acetyl-cysteine, and 3-mercaptopropionic acid) to a biopolymer namely hyaluronic acid (HA) and determined the pKa value of different thiol groups by spectrophotometric analysis. The electron-withdrawing group at the β-position reduced the pKa of the thiol group to 7.0 for HA-cysteine (HA-Cys); 7.4 for N-acetyl cysteine (HA-ActCys) and 8.1 for HA-thiol (HA-SH) derivatives respectively. These experiments further confirmed that the concentration of thiolate (R-S-) ions could be increased with the presence of electron-withdrawing groups, which could facilitate disulfide cross-linked hydrogel formation at physiological pH. Indeed, HA grafted with cysteine or N-acetyl groups formed hydrogels within 3.5 minutes or 10 hours, respectively at pH 7.4. After completion of crosslinking reaction both gels demonstrated a storage modulus G’ ≈3300–3500 Pa, indicating comparable levels of crosslinking. The HA-SH gel, on the other hand, did not form any gel at pH 7.4 even after 24 h. Finally, we demonstrated that the newly prepared hydrogels exhibited excellent hydrolytic stability but can be degraded by cell-directed processes (enzymatic and reductive degradation). We believe our study provides a valuable insight on the factors governing the disulfide formation and our results are useful to develop strategies that would facilitate generation of stable thiol functionalized biomolecules or promote fast thiol oxidation according to the biomedical needs.
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| 9. |
- Bermejo-Velasco, Daniel, et al.
(författare)
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Thiazolidine chemistry revisited : a fast, efficient and stable click-type reaction at physiological pH
- 2018
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Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; 54:88, s. 12507-12510
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Tidskriftsartikel (refereegranskat)abstract
- We describe the fast reaction kinetics between 1,2-aminothiols and aldehydes. Under physiological conditions such a click-type reaction afforded a thiazolidine product that remains stable and did not require any catalyst. This type of bioorthogonal reaction offers enormous potential for the coupling of biomolecules in an efficient and biocompatible manner.
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| 10. |
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