3D Bioprinted Bacteriostatic Hyperelastic Bone Scaffold for Damage-Specific Bone Regeneration

Abstract

Current strategies for regeneration of large bone fractures yield limited clinical success mainly due to poor integration and healing. Multidisciplinary approaches in design and development of functional tissue engineered scaffolds are required to overcome these translational challenges. Here, a new generation of hyperelastic bone (HB) implants, loaded with superparamagnetic iron oxide nanoparticles (SPIONs), are 3D bioprinted and their regenerative effect on large non-healing bone fractures is studied. Scaffolds are bioprinted with the geometry that closely correspond to that of the bone defect, using an osteoconductive, highly elastic, surgically friendly bioink mainly composed of hydroxyapatite. Incorporation of SPIONs into HB bioink results in enhanced bacteriostatic properties of bone grafts while exhibiting no cytotoxicity. In vitro culture of mouse embryonic cells and human osteoblast-like cells remain viable and functional up to 14 days on printed HB scaffolds. Implantation of damage-specific bioprinted constructs into a rat model of femoral bone defect demonstrates significant regenerative effect over the 2-week time course. While no infection, immune rejection, or fibrotic encapsulation is observed, HB grafts show rapid integration with host tissue, ossification, and growth of new bone. These results suggest a great translational potential for 3D bioprinted HB scaffolds, laden with functional nanoparticles, for hard tissue engineering applications.

3D bioprinting of nanoparticle-laden hydrogel scaffolds with enhanced antibacterial and imaging properties

“…Incorporation of nanostructured materials into scaffolding biomaterials has been frequently used to tune or enhance the mechanical properties of engineered tissues ( Corona-Gomez et al., 2016 ; Hasan et al., 2018 ; Shokouhimehr et al., 2021 ). To examine the effect of SPIONs on the mechanical properties of GelMA constructs, we conducted unconfined uniaxial compression and microindentation tests ( Figure 3 , Table S2 ).…”

Hope for bone regeneration: The versatility of iron oxide nanoparticles

“… Three common methods for constructing scaffolds for IONPs. (A) Electrostatic spinning technique ( Khalili et al, 2022 ); (B) freeze-drying technique ( Zhang W. et al, 2019b ); and (C) 3D printing technique ( Shokouhimehr et al, 2021 ). …”

“…3D printing technology offers good stability, 3D spatial structure, and high efficiency, but materials are more restricted and expensive ( Zhao et al, 2014 ). Shokouhimehr et al (2021) 3D printed a new generation of hyperelastic bone (HB) implants loaded with SPIONs applying a bio-ink consisting primarily of HA to scaffolds and studied their therapeutic effect on large non-healing fractures, demonstrating great potential for bone regeneration. The three scaffold fabrication methods and components are shown in Table 2 .…”

Regeneration of Bone Defects in a Rabbit Femoral Osteonecrosis Model Using 3D-Printed Poly (Epsilon-Caprolactone)/Nanoparticulate Willemite Composite Scaffolds

“…This is one of the main goals of bone tissue engineering: the design and fabrication of 3D scaffolds that are not only biocompatible, biodegradable, and specifically porous, but also have a mechanical stability appropriate to bone tissue and additionally possess bioactivity [ 5 , 11 , 12 ]. Nowadays, various classes of materials are available in the field of biomaterial sciences.…”