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Extrusion printing techniques are widely used across tissue engineering and related fields for producing 3D structures from biocompatible thermoplastics, however the achievable structural complexity and porosity can be limited by the nozzle-based, layer-by-layer deposition process. Here we illustrate how this limitation can be overcome through a new technique termed Negative Embodied Sacrificial Template 3D printing. We demonstrate how the negative pattern within a 3D printed object can describe geometries that are not possible to extrusion print directly, and at definitively higher resolution. Negative patterns in a water-soluble sacrificial template can be 'developed' by casting in a secondary material and dissolving the template, creating exquisitely complex 3D structures including hyper-branched dendritic structures and open lattices with stiffnesses tuneable over 3 orders or magnitude. The technique is amenable to a plethora of materials from biodegradable thermoplastics (such as polycaprolactone) to resins (including acrylic and epoxy), silicones (including the Sylgard 184 polydimethylsiloxane formulation), ceramics This article is protected by copyright. All rights reserved. 3(including hydroxyapatite composites), hydrogels (including agarose and gelatin methacryloyl), lowmelt temperature metal alloys and others. Using an unmodified, consumer-grade printer, NEST3D printing achieves high resolution, intricate biomaterial structures with potential applications in biomedical implants and tissue engineering scaffolds.

Osteochondral (OC) defects are debilitating joint injuries characterized by the loss of full thickness articular cartilage along with the underlying calcified cartilage through to the subchondral bone. While current surgical treatments can provide some relief from pain, none can fully repair all the components of the OC unit and restore its native function. Engineering OC tissue is challenging due to the presence of the three distinct tissue regions. Recent advances in additive manufacturing provide unprecedented control over the internal microstructure of bioscaffolds, the patterning of growth factors and the encapsulation of potentially regenerative cells. These developments are ushering in a new paradigm of ‘multiphasic’ scaffold designs in which the optimal micro-environment for each tissue region is individually crafted. Although the adoption of these techniques provides new opportunities in OC research, it also introduces challenges, such as creating tissue interfaces, integrating multiple fabrication techniques and co-culturing different cells within the same construct. This review captures the considerations and capabilities in developing 3D printed OC scaffolds, including materials, fabrication techniques, mechanical function, biological components and design.