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Title: 3D silica-gelatin hybrid scaffolds for tissue regeneration
Author: Nelson, Maria
ISNI:       0000 0001 2442 2150
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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Cartilage defects affect millions of people worldwide however current treatment options do not provide the zonal organisation required to regenerate healthy hyaline cartilage. In particular, the regeneration of high density ECM and cells is required to provide the articular surface of the tissue. Developments in tissue scaffolds have typically focused on synthetic polymers with low bioactivity due to their ease of processing. Here, the silica-gelatin sol-gel hybrid system was further developed for 3D printing and electrospinning to generate a zonal, bioactive scaffold. GPTMS, (3-glycidyloxypropyl)trimethoxysilane, was used to couple the silicate network and gelatin molecules. A modified hybrid method was required to avoid rapid gelation but retain high levels of crosslinking and sol-gel network condensation. To produce the material, the gelatin and GPTMS were mixed for 3 h and 3D printed scaffolds were aged for 1 week at room temperature. The hybrid composition most compatible with the 3D printing process had a 78:22, gelatin to TEOS mass ratio, and C-factor of 500 (molar ratio of GPTMS to gelatin). When 3D printing the gels, a minimum strut separation of 1 mm was achievable. To dry the 3D printed scaffolds, freeze drying and critical point drying resulted in very different structures. Freeze drying produced very thin, < 40 μm struts, and large ~700 μm channels. Critical point drying produced ~160 μm struts and ~200 μm channels which falls within the range hypothesised to be suitable for cartilage regeneration. Electrospinning required further adjustments to the hybrid method to improve the volatility of the solvent. Conformable cotton wool-like fibres with ~1.5 μm diameter were achieved using a 70:30 gelatin to TEOS mass ratio. The C-factors used: 250, 500, and 750, resulted in increasing silica network condensation: 64.3 %, 75.5 %, and 81.1 % respectively. To create the cotton wool-like fibre structure, hybrid solutions with 60-80 cP viscosity were electrospun in 55 % humidity and dried without contacting each other or the collector surface. Both 3D printed and electrospun fibres showed promising dissolution results. The structures were maintained as only ~3 % gelatin was released over a one month study (3D printed) and ~2 %gelatin over a one week study (fibres). The silicon release was ~25 % of the silica content for 3D printed scaffolds, and ~13 % for fibres (CF500 and CF750). The silica-gelatin hybrids were biocompatible and provided native attachment sites for both osteoblasts and chondrocytes. Over 28-days, chondrocytes appeared to regenerate uniform density hyaline cartilage throughout the 3D printed scaffolds in vitro.
Supervisor: Jones, Julian Sponsor: Engineering and Physical Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral