Inkjet printing is a leading technology in the biofabrication of three-dimensional biomaterials, offering digital, noncontact deposition with micron-level precision. Among these materials, hydroxyapatite is widely recognized for its use in bone tissue engineering. However, most hydroxyapatite-laden inks are unsuitable for inkjet printing. To address this, we developed photocurable and biodegradable phosphoramide-based hydrogels containing thiol-functionalized polyethylene glycol via click chemistry. These hydrogels degrade into phosphates, the natural component of bone. The rheological properties of the inks are finely tuned through chemical design to meet the requirements of nanohydroxyapatite composite inks for piezoelectric inkjet printing. We demonstrated their printability using simple geometric patterns, showcasing a versatile and efficient solution for the precise inkjet printing of biomaterial composites.

Three-dimensional (3D) printing of hybrid scaffolds with material gradients, combining soft and hard phases, is an appealing frontier in additive manufacturing. However, most 3D printers are limited to either three-axis or mono-material capabilities, rendering them unsuitable for fabricating hybrid scaffolds. Additionally, printing on curved surfaces requires advanced printing capabilities. Our work aims to advance additive manufacturing by developing a hybrid piezoelectric inkjet-extrusion printer equipped with five-axis functionalities. The printer could be used to fabricate customized hybrid scaffolds, surpassing conventional mono-material or linear three-axis printing strategies. The soft phase comprises a low-viscosity photocurable resin and a high-viscosity peptide hydrogel, while the hard phase comprises 3D-printed polylactic acid and hydroxyapatite parts. To validate the system, we fabricated three hybrid scaffolding use cases, characterized by multi-material porous structures fabricated on planar, single-curved, and free-form surfaces. The scaffolds were subsequently analyzed using digital microscopy to assess their accuracy, particularly the feature sizes of pores and struts (i.e., 0.8–3.6 mm). In the first part of the study, we demonstrated the versatility of inkjet and extrusion printing by hybrid printing an interconnected network in the soft phase on top of a planar ceramic hard phase. A pore width and height deviation of 6% was achieved compared to the intended design. In the second part of the study, we evaluated the 3D inkjet printing of a multi-material porous scaffold on a single-curved surface for osteochondral defects. The circumferential pore width and radial pore height deviated by 0.8% and 2%, respectively. Finally, we inkjet-printed a mesh structure on a free-form surface, which acted as a membrane for palatal implants. In this case, the pore width deviations were -16% in the printing direction and 2% perpendicular to the printing direction.

Additive and lithographic manufacturing technologies using photopolymerisation provide a powerful tool for fabricating multiscale structures, which is especially interesting for biomimetic scaffolds and biointerfaces. However, most resins are tailored to one particular fabrication technology, showing drawbacks for versatile use. Hence, we used a resin based on thiol-ene chemistry, leveraging its numerous advantages such as low oxygen inhibition, minimal shrinkage and high monomer conversion. The resin is tailored to applications in additive and lithographic technologies for future biofabrication where fast curing kinetics in the presence of oxygen are required, namely 3D inkjet printing, digital light processing and nanoimprint lithography. These technologies enable us to fabricate scaffolds over a span of six orders of magnitude with a maximum of 10 mm and a minimum of 150 nm in height, including bioinspired porous structures with controlled architecture, hole-patterned plates and micro/submicro patterned surfaces. Such versatile properties, combined with noncytotoxicity, degradability and the commercial availability of all the components render the resin as a prototyping material for tissue engineers.