Design, fabrication and evaluation of a hybrid biomanufacturing system for tissue engineering

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Abstract

The combined use of additive manufacturing (AM), biocompatible and biodegradable materials, cells and biomolecular signals is the most common biomanufacturing strategy applied in scaffold fabrication. AM processes offer a better control and the ability to actively design the porosity and interconnectivity of the scaffolds. When combined with clinical imaging data, these fabrication techniques can be used to produce constructs that are customised to the shape of the defect or injury. However, due to the hydrophobicity of the commonly used synthetic biopolymers, cell-seeding and proliferation efficiency are limited. Moreover, due to the tortuosity of the scaffolds, non-uniform cell distribution with rare cell adhesion in the core region also commonly exists. Additionally, the commercial available machines are not able to create multi-material and material gradient scaffolds that are required to mimic the nature of nature tissues. To overcome the above limitations, this thesis describes the development of a hybrid bio-additive manufacturing system, called plasma-assisted bioextruson system (PABS), to produce smart scaffold by combining multi-head polymer extrusion and the plasma surface modification layer by layer, in the same chamber. PABS allows not only multiple biomaterials printing with the multi-extrusion heads, but also enables in-process plasma surface modification for zonal plasma-treated scaffolds fabrication. The in-house user interface enables a high degree of scaffold design freedom as it allows users to create single or multi-material constructs with uniform pore size or pore size gradient by changing process parameters such as lay-down pattern, filament distance, feed rate and layer thickness. Water contact angle tests and in vitro biological tests confirm that the hydrophilicity of synthetic polymers is improved and cell attachment and proliferation are enhanced after the in-process plasma modification. The effect of plasma treatment is also investigated by using different plasma modification strategies and various plasma modification parameters, including the plasma deposition velocity and the distance between the plasma jet and the printed scaffolds. The biological results also show dependence between the surface modification strategies and cell proliferation. The mechanical compression results show that for a fixed plasma deposition velocity, the effect of changing the distance between the plasma head and the deposited material is not significant. However, for a fixed distance, the compressive modulus increases with the increase in the plasma deposition velocity.

Keyword(s)

Additive manufacturing; Bioextrusion; Biomanufacturing; Biomedical engineering; PABS; Plasma surface modification; Tissue engineering

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