Design, modelling and fabrication of polycarpolactone electro-active scaffolds for tissue engineering

Abstract

In tissue engineering, scaffolds are physical substrates for cell attachment, proliferation and differentiation, ultimately leading to the regeneration of tissues. They must be designed according to specific biomechanical requirements such as mechanical properties, surface characteristics, biodegradability, biocompatibility and porosity. The optimal design of a scaffold for a specific tissue application strongly depends on both materials and manufacturing processes. Polymeric scaffolds reinforced with electro-active particles could play a key role in tissue engineering by modulating cell proliferation and differentiation. This research project investigates different aspects related to the design, fabrication and evaluation of electro-active scaffolds made with polycaprolactone (PCL) mixed with graphene nanosheets. A series of physical and biological assessments have been performed to assess the properties of produced scaffolds, demonstrating for the first time that 3D printed PCL/graphene scaffolds are suitable for bone tissue engineering. An extrusion-based additive manufacturing system was used to produce the scaffolds allowing a good dispersion of the inorganic component. No significant changes on the surface energy were observed. However, biological assessments suggest that the addition of graphene to PCL enhance the biological behaviour of scaffolds in terms of stimulating cell proliferation and differentiation. Surface treatment with NaOH and zonal plasma treatment strategies increase the hydrophilicity of scaffolds, allowing higher cell attachment rate and ultimately lead to higher cell proliferation rates. Protein bounding to the scaffold also has a positive impact on both cell proliferation and differentiation. Moreover, the immune response analysis of printed scaffolds suggests high potential for in vivo bone regeneration research. Finally, in vivo tests show that the use of PCL/graphene scaffolds with exogenous microcurrent therapy enhance new tissue formation, stimulating the levels of ALP, RANK and higher ratios between OPG and RANKL. The physiological electrical stimulation modulated the bone remodelling phase, leading to well-organized and mineralized tissue deposition. Generally speaking, both non-biological and biological (including in vitro and in vivo) assessments have presented improved bone regeneration effect compared with conventional PCL scaffolds. All the results present in dissertation suggest a promising future for the in-depth clinical study on this newly developed 3D structure for the speed up of large scale bone tissue regeneration.

Date of Award	1 Aug 2019
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Parthasarathi Mandal (Supervisor), Paulo Jorge Da Silva Bartolo (Supervisor) & Marco Domingos (Supervisor)