3D Printed Engineered Nano-Composite Templates for Bone Regeneration

The overarching objective of the “3DPRENT? project is to facilitate translation of the 3D printing technology for bone regeneration. Three-dimensional (3D) bioprinting is seen as a potential new solution to create personalized bone-like constructs. However, lack of ideal bioinks is a considerable issue in 3D bioprinting, as various requirements related to cell function and printability of the bioinks exist. Tissue-specific hydrogels made from different formulations of natural polymers have been developed by the team. The developed biomaterial inks have been characterized for their material properties in terms of rheology, stability, and printability. Biological characterization composed of 3D bioprinting pilot, where human bone marrow derived mesenchymal stem cells were bioprinted in one bioink to optimize the crosslinking conditions in terms of cell viability and proliferation. Cytotoxicity of the materials and bioprinting process was evaluated. Furthermore, freeze-dried porous scaffolds were prepared using nano hydroxyapatite (nHA) and wood-derived cellulose nanofibrils (CNF). The results imply that 20 % nHA scaffolding has the greatest potential for further biomimetic bone tissue engineering investigations.

Recent clinical studies performed by our group and other clinical partners in Europe, propose alternatives to conventional treatment modalities by using the concept of tissue engineering in which engineered biomaterials (scaffolds) are used to deliver mesenchymal stem cells (MSC) and/or growth factors. Although there have been some successes, bone tissue engineering needs to overcome several challenges to meet clinical and commercialization needs. Among these challenges, the limitations of scaffolding biomaterials to mimic the macro to nanoscale structures of native tissues. Current bone scaffolds suffer from impaired cellular responses, inadequate delivery of growth factors, insufficient mechanical strength and incorrect design. The significance of the current project lies on combining nanotechnology and 3D printing technology. The synergetic impact of such integrated technologies has a potential to advance the field of bone tissue engineering by developing biomimetic multiscale multifunctional scaffolds for enhanced cell response and growth factor delivery. In 3DPRENT, oxidized cellulose nanofibers (CNF)-based hydrogel will be functionalized with nano-hydroxyapatite (nHA) for osteoconductivity, nanodiamond particles (nDP) to deliver vascular endothelial growth factor (VEGF) and finally to bioprint mesenchymal stem cells (MSC). For mechanical stability and vascularization, hydrogel layers will be reinforced with 3D printed microchannel network of a thermoplastic polymer modified with (nHA). The bioengineered constructs will be fabricated based on computational model-informed design, cultured in a dynamic in vitro conditions and finally validated in relevant pre-clinical animal models. 3DPRENT will develop not only outstanding basic scientific knowledge but also sustainable solutions and innovations based on nanotechnology, 3D printing and stem cells thus improving health and promoting new medical technology to meet the needs of society.