3D printed hydrogel scaffolds for meniscal implant application: photo-crosslinkable urethane-based poly(ethylene glycol) as a case study

Abstract

The meniscus is one of the most injured structures in the human knee. Current clinical approaches do not adequately replace or regenerate the meniscus. Complete or partial meniscus removal leads to degenerative articular changes due to abnormal mechanical forces. Tissue engineering (TE) of the meniscus or developing non-tissue-engineered implants may offer efficient solutions. Yet, these approaches are challenging due to the requirement of a complex, non-toxic three-dimensional (3D) structure exhibiting adequate biomechanical and biological properties. In this study, we developed a porous 3D printed acrylate end-capped urethane-based poly(ethylene glycol) (AUP) hydrogel scaffold via extrusion-based 3D printing for meniscus implant application. With the aim to meet the required biomechanical properties, we studied the effects of two different scaffold variables. Indeed, in addition to the poly(ethylene glycol) (PEG) backbone molar mass (4000 versus 8000 g mol⁻¹), we also varied the scaffold design. The latter included variations in the scaffold pore size (200 µm, 350 µm and 500 µm) and the strut diameter (230 µm versus 370 µm). The morphology of the developed AUP hydrogel scaffolds was characterized via optical microscopy and nano-computed tomography (nano-CT), showing regular, porous, interconnected 3D hydrogel scaffolds. The physical properties of the scaffolds, including the gel fraction (75–89%), the swelling degree (230–500%) and the compressive modulus (0.5–3.2 MPa), depended on the scaffold design and the backbone molar mass. Surface analyses through X-ray photoelectron spectroscopy (XPS) showed the successful application of a photo-crosslinkable gelatin derivative (known as gel-MOD or gel-MA) on the printed AUP hydrogel scaffolds (as reflected by an N/C value of 0.06 for gel-MOD modified AUP versus no signal for non-modified AUP scaffolds). Live/dead staining and the MTT assay using human dermal fibroblasts (HDF) revealed the non-toxic behavior of the developed AUP scaffolds (90% cell viability). This study clearly demonstrates the potential of the developed AUP hydrogel scaffolds as meniscal implants, as the applied polymer and 3D printing technologies enable the development of non-toxic 3D porous scaffolds, of which both the cell-interactive character and the mechanical properties can be controlled.