Bioengineered Living Bone Grafts—A Concise Review on Bioreactors and Production Techniques In Vitro

Abstract

It has been observed that bone fractures carry a risk of high mortality and morbidity. The deployment of a proper bone healing method is essential to achieve the desired success. Over the years, bone tissue engineering (BTE) has appeared to be a very promising approach aimed at restoring bone defects. The main role of the BTE is to apply new, efficient, and functional bone regeneration therapy via a combination of bone scaffolds with cells and/or healing promotive factors (e.g., growth factors and bioactive agents). The modern approach involves also the production of living bone grafts in vitro by long-term culture of cell-seeded biomaterials, often with the use of bioreactors. This review presents the most recent findings concerning biomaterials, cells, and techniques used for the production of living bone grafts under in vitro conditions. Particular attention has been given to features of known bioreactor systems currently used in BTE: perfusion bioreactors, rotating bioreactors, and spinner flask bioreactors. Although bioreactor systems are still characterized by some limitations, they are excellent platforms to form bioengineered living bone grafts in vitro for bone fracture regeneration. Moreover, the review article also describes the types of biomaterials and sources of cells that can be used in BTE as well as the role of three-dimensional bioprinting and pulsed electromagnetic fields in both bone healing and BTE.

In Vivo Bone Tissue Engineering Strategies: Advances and Prospects

“…Kazimierczak et al recommend to seed the scaffold with various types of cells for creating a functional vascularized bone graft in vitro. Authors used co-cultures of mesenchymal stem cells with endothelial cells to produce such a graft [ 158 ]. Currently, bioprinting-based vascularization strategy represents the most advanced technology of vascular network creation.…”

“…Bioreactors have been developed as essential devices for in vitro tissue engineering purposes to provide physiological tissue-specific environment by mimicking in vivo conditions for tissue growth and regeneration [ 158 , 160 , 161 , 162 ]. Various types of bioreactors for tissue engineering have been developed and applied in recent years.…”

“…Spinner Flask Bioreactors are composed of a media reservoir with two side arms with filter caps for gas exchange. Such a device design provides a convective flow and produces hydrodynamic forces to enhance mass transport [ 158 , 162 ]. It can effectively mimic important aspects of native bone environment and can positively affect accelerating human mesenchymal stem cells osteogenic differentiation [ 162 ].…”

“…Pulsed Electromagnetic Fields-Based Bioreactors have been recently applied as an effective treatment option in orthopedic clinical practice to support bone healing in patients with non-union or delayed-union bone fractures [ 158 , 171 ]. Furthermore, pulsed electromagnetic fields demonstrated efficiency in osteonecrosis and diabetic osteopenia treatment [ 172 ], and accelerate migration and osteogenic differentiation of mesenchymal stem cells, as well as osteoblast proliferation and differentiation in vitro [ 173 ].…”

Strontium Peroxide-Loaded Composite Scaffolds Capable of Generating Oxygen and Modulating Behaviors of Osteoblasts and Osteoclasts

“…However, the utilization of bone autografts remains limited by several drawbacks, such as the creation of secondary surgical sites, limited availability of graft tissue, and substantial donor site complications [ 2 , 5 ]. To address these issues, researchers have made major efforts to develop biomaterial- and composite-based bone grafts [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. As native bone tissue is mainly composed of mineralized collagen fibrils, collagen and its derivatives have been extensively investigated as bone substitutes owing to their excellent biocompatibility and biodegradability [ 13 ].…”