Bioprinting of Hydrogels onto Structural Biomaterials for Bioactive Interfaces

Abstract

Metals, polymers, ceramics and composites are classes of biomaterials used for implants. Each of those has an exceptional set of properties desired for various biomedical applications but also limitations driving a clinical need to propose new and innovative solutions within the tissue engineering field. Bioprinting has emerged in recent years as an attractive set of methods for co-processing cells and hydrogel biomaterials for the fabrication of three-dimensional (3D) cell-laden constructs. Combining hydrogels with structural biomaterials offers the potential to create functional tissue-engineered implants with enhanced bioactivity. Working towards this end, this project aimed to exploit a bioprinting technique called Reactive Jet Impingement (ReJI) as a method to integrate cell-laden hydrogels with various biomaterial substrates. The use of ReJI bioprinting for bone and skin tissue engineering applications was considered. The biological response of bioprinted mesenchymal stromal cells (MSCs) in collagen-alginate-fibrin (CAF) hydrogels onto titanium alloy Ti6Al4V substrates with various surface roughness and morphology was studied. The cell-laden hydrogels support the formation of a layer of functional bone-like tissue at the surface of metal substrates. A binder jetting process was deployed to develop apatite-wollastonite (AW) bioceramic scaffolds for the ReJI bioprinting. The scaffolds are characterised by an interconnected network of pores that enables penetration and mineralisation of both manually seeded MSCs and bioprinted MSCs in a CAF hydrogel matrix. Cell-hydrogel-microfibre composites were produced by bioprinting human fibroblasts in a CAF hydrogel matrix onto fibre-based substrates made of calcium alginate for potential wound healing. The cell-hydrogel-microfibre composites maintain high cell viability and promote cell-cell and cell-biomaterial interactions. Overall this research demonstrates the suitability of ReJI bioprinting to enhance the bioactivity of structural biomaterials by delivering high cell concentrations within hydrogels at the interface across a wide range of surface chemistries and topographies.