Biofabrication of customized bone grafts by combination of additive manufacturing and bioreactor knowhow

Abstract

This study reports on an original concept of additive manufacturing for the fabrication of tissue engineered constructs (TEC), offering the possibility of concomitantly manufacturing a customized scaffold and a bioreactor chamber to any size and shape. As a proof of concept towards the development of anatomically relevant TECs, this concept was utilized for the design and fabrication of a highly porous sheep tibia scaffold around which a bioreactor chamber of similar shape was simultaneously built. The morphology of the bioreactor/scaffold device was investigated by micro-computed tomography and scanning electron microscopy confirming the porous architecture of the sheep tibiae as opposed to the non-porous nature of the bioreactor chamber. Additionally, this study demonstrates that both the shape, as well as the inner architecture of the device can significantly impact the perfusion of fluid within the scaffold architecture. Indeed, fluid flow modelling revealed that this was of significant importance for controlling the nutrition flow pattern within the scaffold and the bioreactor chamber, avoiding the formation of stagnant flow regions detrimental for in vitro tissue development. The bioreactor/scaffold device was dynamically seeded with human primary osteoblasts and cultured under bi-directional perfusion for two and six weeks. Primary human osteoblasts were observed homogenously distributed throughout the scaffold, and were viable for the six week culture period. This work demonstrates a novel application for additive manufacturing in the development of scaffolds and bioreactors. Given the intrinsic flexibility of the additive manufacturing technology platform developed, more complex culture systems can be fabricated which would contribute to the advances in customized and patient-specific tissue engineering strategies for a wide range of applications.

Additively Manufactured Device for Dynamic Culture of Large Arrays of 3D Tissue Engineered Constructs

“…The chambers were chamfered 2 mm with an angle of 45° (Figure 1 c) to eliminate low fl uid velocity regions (white arrows in Figure 1 a,b) as demonstrated in our previous work. [ 8 ] This confi guration combining the ABS support structure and the chamfered chambers maintained a homogeneous fl uid fl ow velocity throughout the scaffold ranging from 10% to 15% of the initial fl ow rate ( Figure 1 c). At the inlet of each individual chamber, the fl ow rate was 0.1 mL min -1 and therefore, the fl ow rate in the scaffold ranged from 0.01-0.015 mL min -1 ( Figure 1 c), which is in agreement with optimal fl ow rates reported in other studies.…”

“…[ 7 ] In a previous report, [ 8 ] we utilized this technology for fabricating an anatomically relevant device comprising a porous scaffold replica of an ovine tibia around which a bioreactor chamber of similar shape was simultaneously built. We hypothesized that this concept could be further utilized in large-scale cell culture studies while circumventing the aforementioned issues associated with the use of traditional bioreactors.…”

3D printing of biomaterials

“…3 The application of AM represents one of the most rapidly advancing areas of biomedical sciences in which engineers, scientists, and clinicians are contributing to the future of human health care and, more specifi cally, to areas of medical devices, tissue engineering (TE), regenerative medicine (RM), and in vitro disease model development. 4 There is an increasing trend of single groups or larger research consortia inventing their own defi nitions and terminology, which often makes it diffi cult to fi nd and compare the results of the published work. Therefore, to move the fi eld constructively forward, it is a condition sine qua non to clarify terms such as biomanufacturing, biofabrication, bioprinting, and cell printing, which are often used interchangeably in the literature.…”

“…3 This is also the year when researchers from Oak Ridge National Laboratory built a complete car body using a 3D printing technique known as big area additive manufacturing and partnered with Local Motors to commission and drive a functional car at the International Manufacturing Technology Show. 4 Threedimensional printing-based agile manufacturing technologies are promoting on-demand production with traditional as well as innovative designs that are diffi cult, if not impossible, to make through conventional manufacturing (CM) approaches. Three-dimensional printing technologies are also making a signifi cant impact in biomedical research-from device designs to tissue engineering (TE) to bioprinting and drug delivery, which is the focus of this issue of MRS Bulletin .…”

Bone Tissue Engineering Drug Delivery

“…By having the BMP-printed implant's face positioned either away or directly facing the mouse's dura mater (source of osteoprogenitor cells), it was possible to verify that direct contact of the printed BMP-2 with the underlying dura mater resulted in greater percentage of bone formation. In the particular case of 3D printing, this technology has recently become quite attractive within tissue engineering strategies due to its ability to easily generate 3D constructs in virtually any shape, architecture, size, and number [45,46]. 3D printed scaffolds have often been modified/functionalized in order to improve their osteogenic properties by means of postprocessing strategies such as, i.e., surface deposition of Fig.…”