AbstractBone is primarily made of type I collagen, which is a highly abundant natural protein. Collagen can be crosslinked through several methods including chemical agents, physical heating and UV radiation. The result is enhanced physical characteristics such as thermal stability, resistance to proteolytic breakdown, mechanical strength and increased overall biocompatibility. However, with these methods there are drawbacks; including toxicity of residual cross-linking agents, or difficulties with scaling. In recent years, collagen has been cross-linked by a safer, efficient and more practical means by using enzymes as biological catalysts.
We demonstrate that crosslinking native collagen with both tissue transglutaminase (TG2) and microbial transglutaminase (mTG- from Streptoverticillium mobaraense) leads to an increase in the proliferation of human osteoblasts (HOB) and an increase in integrins on their cell surface compared to culture on native collagen. These integrins include αV, α5, β1 and β3 which are all important for the ability of HOBs to mature and differentiate. In addition to this, the HOBs were shown to mineralise at a faster rate than on native collagen. Moreover, it was demonstrated that integrin expression and mineralisation rates are further increased in HOBs on crosslinked collagen by incorporating 45S5 bioglass particles.
Investigations here show distinct differences between the micro-structure of the scaffolds and the mean pore size between fibrils in native and crosslinked collagen. These results suggest that the crosslinked collagen changes the behaviour of HOBs when seeded, such that through the Wnt canonical pathway there is an overall increased drive towards mineralisation and deposition of collagen by the HOBs.
This work shows that crosslinked collagen scaffolds with 45S5 bioglass have the potential to be used as biomaterials for bone regeneration and may eventually replace allografts and titanium plates.
|Date of Award||21 Mar 2019|
|Supervisor||Russell Collighan (Supervisor) & Richard Martin (Supervisor)|
Novel collagen- based biomaterials for bone regeneration
Choudhery, H. (Author). 21 Mar 2019
Student thesis: Doctoral Thesis › Doctor of Philosophy