Hyaluronan Hydrogels Combined with Collagen I Aimed for Corneal Regeneration
Sorsa, Eetu (2017)
2017
Materiaalitekniikka
Teknisten tieteiden tiedekunta - Faculty of Engineering Sciences
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Hyväksymispäivämäärä
2017-06-07
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tty-201705241510
https://urn.fi/URN:NBN:fi:tty-201705241510
Tiivistelmä
Millions of people worldwide suffer from corneal blindness, with many of them facing the global shortage of high quality donor corneas. A variety of artificial corneas have been developed to combat this problem, and a few have already reached commercial level. Natural polymers have shown potential as materials for tissue-engineered corneas due to their good biocompatibility, availability and typically mild reaction conditions. The aim of this thesis was to develop and characterise two hyaluronan hydrogels with and without rat tail collagen I to be used as scaffolds for the regeneration of the corneal stroma.
The hyaluronan components were modified to achieve two different types of hydrazone crosslinking. The hydrazide components of type A gels were modified using adipic acid dihydrazide (ADH), and the ones of type B with carbodihydrazide (CDH), both with their corresponding aldehyde derivatives. The collagenous and non-collagenous hydrogels were distinguished using suffixes 1 and 2. The characterisation itself consisted of me-chanical, viscoelastic and optical analyses, as well as stability, degradation and swelling measurements. Cell viability tests guiding the development were conducted by a collab-orating research group alongside the material optimisation process.
The mechanical characteristics were expressed using second order elastic constants. The average values for gels A1 and A2 in respective order were (5.4 ± 1.1) kPa and (2.9 ± 1.1) kPa, and the ones for gels B1 and B2 were (6.7 ± 1.0) kPa and (7.3 ± 1.1) kPa. The addition of collagen produced somewhat conflicting results, since it improved the me-chanical resilience of type B gels and weakened type A gels, indicating that collagen might have interfered with the crosslinking efficiency of the polymers. The CDH-modi-fied type B gels showed improved stability and controlled swelling behaviour in the phys-iological environment. All the gels were transparent and with refractive indices between 1.33 and 1.34, which is slightly lower than the one of the corneal stroma (1.38). Type B gels had higher refractive indices than type A, presumably due to their higher crosslink density. Preliminary results from custom transmittance measurements showed slightly decreased transparency in the collagenous gels, as was expected. Collagen-content also decreased the swelling as well as the rate of enzymatic degradation in both gel types.
The results showed that the CDH-modified hyaluronan hydrogels were significantly more stable in the cell culture medium and had superior mechanical and optical properties com-pared to the ADH-modified gels. Based on the results, type B gels could have potential to be developed into hydrogels for corneal regeneration in the future. However, further examination would still be necessary on the collagen used in this study.
The hyaluronan components were modified to achieve two different types of hydrazone crosslinking. The hydrazide components of type A gels were modified using adipic acid dihydrazide (ADH), and the ones of type B with carbodihydrazide (CDH), both with their corresponding aldehyde derivatives. The collagenous and non-collagenous hydrogels were distinguished using suffixes 1 and 2. The characterisation itself consisted of me-chanical, viscoelastic and optical analyses, as well as stability, degradation and swelling measurements. Cell viability tests guiding the development were conducted by a collab-orating research group alongside the material optimisation process.
The mechanical characteristics were expressed using second order elastic constants. The average values for gels A1 and A2 in respective order were (5.4 ± 1.1) kPa and (2.9 ± 1.1) kPa, and the ones for gels B1 and B2 were (6.7 ± 1.0) kPa and (7.3 ± 1.1) kPa. The addition of collagen produced somewhat conflicting results, since it improved the me-chanical resilience of type B gels and weakened type A gels, indicating that collagen might have interfered with the crosslinking efficiency of the polymers. The CDH-modi-fied type B gels showed improved stability and controlled swelling behaviour in the phys-iological environment. All the gels were transparent and with refractive indices between 1.33 and 1.34, which is slightly lower than the one of the corneal stroma (1.38). Type B gels had higher refractive indices than type A, presumably due to their higher crosslink density. Preliminary results from custom transmittance measurements showed slightly decreased transparency in the collagenous gels, as was expected. Collagen-content also decreased the swelling as well as the rate of enzymatic degradation in both gel types.
The results showed that the CDH-modified hyaluronan hydrogels were significantly more stable in the cell culture medium and had superior mechanical and optical properties com-pared to the ADH-modified gels. Based on the results, type B gels could have potential to be developed into hydrogels for corneal regeneration in the future. However, further examination would still be necessary on the collagen used in this study.