| 2. |
- Piskounova, Sonya
(författare)
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Biomaterials for Promoting Self-Healing of Bone Tissue
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present work addresses poor bone/implant integration and severe bone defects. In both conditions external stimuli is required for new bone to form. A multilayered functional implant coating, comprised of an inner layer of crystalline titanium dioxide (TiO2) and an outer layer of hydroxyapatite (HAP), loaded with bone morphogenetic protein-2 (BMP-2), was proposed as a tool for providing both improved initial bone formation and long-term osseointegration. The in vitro characterization of the implant coatings showed that TiO2 and HAP were more favorable for cell viability, cell morphology and initial cell differentiation, compared to native titanium oxide. Furthermore, significantly higher cell differentiation was observed on surfaces with BMP-2, indicating that a simple soaking process can be used for incorporating bioactive molecules. Moreover, the results suggest that there could be a direct interaction between BMP-2 and HAP, which prolongs the retention of the growth factor, improving its therapeutic effect. For treating severe bone defects a strategy involving BMP-2 delivery from hyaluronan hydrogels was explored. The hydrogels were prepared from two reactive polymers – an aldehyde-modified hyaluronan and a hydrazide-modified poly(vinyl alcohol). Upon mixing, the two components formed a chemically crosslinked hydrogel. In this work the mixing of the hydrogel components was optimized by rheological measurements. Furthermore, an appropriate buffer was selected for in vitro experiments by studying the swelling of hydrogels in PBS and in cell culture medium. A detection method, based on radioactive labeling of BMP-2 with 125I was used to monitor growth factor release both in vitro and in vivo. The results showed a biphasic release profile of BMP-2, where approximately 16 % and 3 % of the growth factor remained inside the hydrogel after 4 weeks in vitro and in vivo, respectively. The initial fast release phase corresponded to the early ectopic bone formation observed 8 d after injection of the hydrogel formulation in the thigh muscle of rats. The hydrogel formulation could be improved by incorporation of HAP powder into the hydrogel formulation. Furthermore, bone formation could be increased by pre-incubation of the premixed hydrogel components inside the syringe prior to injection. Crushed hydrogels were also observed to induce more bone formation compared to solid hydrogels, when implanted subcutaneously in rats. This was thought to be due to increased surface area of the hydrogel, which allowed for improved cell infiltration.
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| 3. |
- Piskounova, Sonya, et al.
(författare)
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The Effect of Mixing on the Mechanical Properties of Hyaluronan-Based Injectable Hydrogels
- 2011
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Ingår i: Macromolecular materials and engineering. - : Wiley. - 1438-7492 .- 1439-2054. ; 296:10, s. 944-951
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Tidskriftsartikel (refereegranskat)abstract
- A method for determining the correlation between the mixing of two reactive polymers and the structural and mechanical properties of the formed hydrogels is presented. Rheological measurements show that insufficient mixing gives rise to soft and not fully crosslinked hydrogels while excessive mixing beyond gel point results in weaker hydrogels due to potential breakage of their 3D network. Furthermore, the hydrogels swell significantly more in cell culture medium than in phosphate-buffered saline, attributed to interactions with additional molecules such as proteins. Thus, moderate mixing gives rise to the most homogenous and mechanically stable hydrogels and the choice of medium e.g., for release experiments, should be consistent in order to avoid unnecessary variations in the data caused by different swelling profiles.
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