| 1. |
- Ravichandran, Ranjithkumar, et al.
(författare)
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Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications
- 2016
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Ingår i: Journal of materials chemistry. B. - : ROYAL SOC CHEMISTRY. - 2050-750X .- 2050-7518. ; 4:2, s. 318-326
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we derivatized type I collagen without altering its triple helical conformation to allow for facile hydrogel formation via the Michael addition of thiols to methacrylates without the addition of other crosslinking agents. This method provides the flexibility needed for the fabrication of injectable hydrogels or pre-fabricated implantable scaffolds, using the same components by tuning the modulus from Pa to kPa. Enzymatic degradability of the hydrogels can also be easily fine-tuned by variation of the ratio and the type of the crosslinking component. The structural morphology reveals a lamellar structure mimicking native collagen fibrils. The versatility of this material is demonstrated by its use as a pre-fabricated substrate for culturing human corneal epithelial cells and as an injectable hydrogel for 3-D encapsulation of cardiac progenitor cells.
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| 2. |
- Kristensen, Emma, et al.
(författare)
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Photoelectron spectroscopy studies of the functionalization of a silicon surface with a phosphorylcholine-terminated polymer grafted onto (3-aminopropyl)trimethoxysilane
- 2006
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 22:23, s. 9651-9657
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Tidskriftsartikel (refereegranskat)abstract
- The structure of a biomimetic phosphorylcholine (PC)-functionalized poly(trimethylene carbonate) (PC-PTMC-PC), linked to a silicon substrate through an aminolysis reaction at 120 degrees C with (3-aminopropyl) trimethoxysilane (APTMS), was studied using photoelectron spectroscopy. Two chemical states were found for the unreacted APTMS amine, a neutral state and a protonated state, where the protonated amine on average was situated closer to the silicon substrate than the neutral amine. The experiments also indicated the presence of a third chemical state, where amines interact with unreacted silanol groups. The PTMC chains of the grafted films were found to consist of only 2-3 repeat units, with the grafted chains enriched in the zwitterionic end group, suggesting that these groups are attracted to the surface. This was further supported by the experiments showing that the PC groups were situated deeper within the film.
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| 3. |
- 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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| 4. |
- Martinez-Sanz, Elena, et al.
(författare)
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Bone reservoir : Injectable hyaluronic acid hydrogel for minimal invasive bone augmentation
- 2011
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 152:2, s. 232-240
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Tidskriftsartikel (refereegranskat)abstract
- A strategy has been designed to develop hyaluronic acid (HA) hydrogel for in vivo bone augmentation using minimal invasive technique. A mild synthetic procedure was developed to prepare aldehyde modified HA by incorporating an amino-glycerol side chain via amidation reaction and selective oxidation of the pendent group. This modification, upon mixing with hydrazide modified HA formed hydrazone-crosslinked hydrogel within 30 s that was stable at physiological pH. In vitro experiments showed no cytotoxicity of hydrogel with the controlled release of active bone morphogenic protein-2 (BMP-2). In vivo evaluation of this gel as a BMP-2 carrier was performed by injecting gels over the rat calvarium and showed bone formation in 8 weeks in correlation with the amount of BMP-2 loaded (0, 1 and 30 pig) within the gel. Furthermore, hydrogels with 30 Kg of BMP-2 induced less bone formation upon subcutaneous injection in comparison with subperiosteal implantation. Histological examination showed newly formed bone with a high expression of osteocalcin, osteopontin and with angiogenic bone marrow when higher BMP-2 concentration was employed. Our result suggests that novel HA hydrogels could be used as a BMP-2 carrier and can promote bone augmentation for potential orthopedic applications.
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| 5. |
- Aulin, Cecilia, 1979-
(författare)
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Extracellular Matrix Based Materials for Tissue Engineering
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The extracellular matrix is (ECM) is a network of large, structural proteins and polysaccharides, important for cellular behavior, tissue development and maintenance. Present thesis describes work exploring ECM as scaffolds for tissue engineering by manipulating cells cultured in vitro or by influencing ECM expression in vivo. By culturing cells on polymer meshes under dynamic culture conditions, deposition of a complex ECM could be achieved, but with low yields. Since the major part of synthesized ECM diffused into the medium the rate limiting step of deposition was investigated. This quantitative analysis showed that the real rate limiting factor is the low proportion of new proteins which are deposited as functional ECM. It is suggested that cells are pre-embedded in for example collagen gels to increase the steric retention and hence functional deposition. The possibility to induce endogenous ECM formation and tissue regeneration by implantation of growth factors in a carrier material was investigated. Bone morphogenetic protein-2 (BMP-2) is a growth factor known to be involved in growth and differentiation of bone and cartilage tissue. The BMP-2 processing and secretion was examined in two cell systems representing endochondral (chondrocytes) and intramembranous (mesenchymal stem cells) bone formation. It was discovered that chondrocytes are more efficient in producing BMP-2 compared to MSC. The role of the antagonist noggin was also investigated and was found to affect the stability of BMP-2 and modulate its effect. Finally, an injectable gel of the ECM component hyaluronan has been evaluated as delivery vehicle in cartilage regeneration. The hyaluronan hydrogel system showed promising results as a versatile biomaterial for cartilage regeneration, could easily be placed intraarticulary and can be used for both cell based and cell free therapies.
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| 6. |
- Engelhardt, Eva-Maria, et al.
(författare)
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A collagen-poly(lactic acid-co-epsilon-caprolactone) hybrid scaffold for bladder tissue regeneration
- 2011
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 32:16, s. 3969-3976
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Tidskriftsartikel (refereegranskat)abstract
- Scaffold materials should favor cell attachment and proliferation, and provide designable 3D structures with appropriate mechanical strength. Collagen matrices have proven to be beneficial scaffolds for tissue regeneration. However, apart from small intestinal submucosa, they offer a limited mechanical strength even if crosslinking can enhance their mechanical properties. A more cell-friendly way to increase material strength is to combine synthetic polymer meshes with plastic compressed collagen gels. This work describes the potential of plastic compressed collagen poly(lactic acid-co-epsilon-caprolactone) (PLAC) hybrids as scaffolds for bladder tissue regeneration. Human bladder smooth muscle and urothelial cells were cultured on and inside collagen PLAC hybrids in vitro. Scaffolds were analyzed by electron microscopy, histology, immunohistochemistry, and AlamarBlue assay. Both cell types proliferated in and on the hybrid, forming dense cell layers on top after two weeks. Furthermore, hybrids were implanted subcutaneously in the backs of nude mice. Host cell infiltration, scaffold degradation, and the presence of the seeded bladder cells were analyzed. Hybrids showed a lower inflammatory reaction in vivo than PLAC meshes alone, and first signs of polymer degradation were visible at six months. Collagen PLAC hybrids have potential for bladder tissue regeneration, as they show efficient cell seeding, proliferation, and good mechanical properties.
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| 7. |
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| 8. |
- Sugunan, Abhilash, et al.
(författare)
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Nutrition-Driven Assembly of Colloidal Nanoparticles : Growing fungi assemble gold nanoparticles as microwires
- 2007
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Ingår i: Advanced Materials. - Weinheim, Germany : Wiley. - 0935-9648 .- 1521-4095. ; 19:1, s. 77-81
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Tidskriftsartikel (refereegranskat)abstract
- The use of a living fungus to 'actively' assemble presynthesized gold nano-particles over its hyphae, resulting in conducting microstructures (see figure), is reported. This physiologically (nutrition) driven process of colloidal self-organization avoids the need for sophisticated DNA/protein chemistry for facilitating interfacing with biological surfaces. The obtained gold-laden microstructures can be modified into flat ribbonlike or tubular morphologies by simple post-formation processing.
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| 9. |
- Yang, Xia, et al.
(författare)
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Preparation of hyaluronic acid nanoparticles via hydrophobic association assisted chemical cross-linking : an orthogonal modular approach
- 2011
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 7:16, s. 7517-7525
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to develop an efficient and stable drug delivery nanocarrier based on a dually functionalized hyaluronic acid (HA) derivative which could be used as a long circulating drug delivery vehicle. Self-assembled HA nanoparticles (HA NPs) were prepared by attaching pyrene to the HA backbone and the obtained physical NPs were stabilized by chemical cross-linking of the HA chains to form hydrophobic core-hydrophilic shell NPs. Orthogonal chemoselective reactions were applied for conversion of HA into its amphiphilic derivative and subsequent cross-linking of the formed micellar-type associates. Chemical stabilization of the physical HA associates afforded therefore very stable nanoparticles that could easily be re-suspended in aqueous media after freeze-drying. In contrast, freeze-drying of the uncross-linked physically associated particles resulted in a non-soluble material. Doxorubicin (DOX), a typical anticancer drug, was entrapped into HA NPs via ionic and/or hydrophobic interactions and used for in vitro drug release. Higher loading efficiency and the slower release profile of DOX from HA NPs were obtained with the hydrophobically encapsulated drug. We have shown that free HA NPs were readily taken up by NIH 3T3 cells without causing any toxicity to the cells, while the DOX-loaded HA NPs resulted in increased cell death comparable to the free drug. This study clearly showed the applicability of orthogonal chemoselective modifications for the synthesis of stable HA nanogel particles as a potential cancer-targeted drug delivery system.
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| 10. |
- Atthoff, Björn, et al.
(författare)
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Polarized protein membrane for high cell seeding efficiency
- 2007
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Ingår i: Journal of Biomedical Materials Research - Part B Applied Biomaterials. - : Wiley. - 1552-4973 .- 1552-4981. ; 83:2, s. 472-480
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Tidskriftsartikel (refereegranskat)abstract
- A new type of scaffold for tissue engineering was developed to give enhanced cell seeding in three dimensions. A gradient of either collagen or fibrin protein was prepared, supported by a knitted poly(ethylene terephtalate) PET fabric. The membranes were, after hydrolysis and acetic acid wash, submerged in a protein solution for adsorption followed by immersion into a gelling agent. The immediate contact between the protein solution held by the fabric and the gelling agent resulted in a dense, fibrous protein network with pore sizes around 0.5 μm at the surface, and larger pores of 10-50 μm size throughout the interior of the fabric as observed by scanning electron microscopy. By separating the fabric double layers holding this network, a gradient porosity membrane was produced. To evaluate the fractions of cells trapped in the matrix upon seeding, i.e. the seeding efficiency, 500 μl 3T3 fibroblasts cell suspension containing one million cells was seeded by filtering through the gradient protein membrane. For both the collagen and fibrin membranes, the seeding efficiency was ∼93%, which was significantly higher than that of 28% from the corresponding PET fabric without protein immobilization. Attempt to seed cells from the dense side of the protein networks resulted in no cell penetration into the scaffold. Histology on subsequent culture of the cells in the scaffold demonstrated viability and proliferation in three dimensions throughout the scaffold. This new and simple way of producing scaffolds play an important role when the cells are precious or scarce and cell seeding in three dimensions is important.
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