Veli Ozbolat

Application areas of 3D bioprinting.

Three dimensional (3D) bioprinting has been a powerful tool in patterning and precisely placing biologics, including living cells, nucleic acids, drug particles, proteins and growth factors, to recapitulate tissue anatomy, biology and physiology. Since the first time of cytoscribing cells demonstrated in 1986, bioprinting has made a substantial leap forward, particularly in the past 10 years, and it has been widely used in fabrication of living tissues for various application areas. The technology has been recently commercialized by several emerging businesses, and bioprinters and bioprinted tissues have gained significant interest in medicine and pharmaceutics. This Keynote review presents the bioprinting technology and covers a first-time comprehensive overview of its application areas from tissue engineering and regenerative medicine to pharmaceutics and cancer research.

3D bioprinting for drug discovery and development in pharmaceutics

Successful launch of a commercial drug requires significant investment of time and financial resources wherein late-stage failures become a reason for catastrophic failures in drug discovery. This calls for infusing constant innovations in technologies, which can give reliable prediction of efficacy, and more importantly, toxicology of the compound early in the drug discovery process before clinical trials. Though computational advances have resulted in more rationale in silico designing, in vitro experimental studies still require gaining industry confidence and improving in vitro-in vivo correlations. In this quest, due to their ability to mimic the spatial and chemical attributes of native tissues, three-dimensional (3D) tissue models have now proven to provide better results for drug screening compared to traditional two-dimensional (2D) models. However, in vitro fabrication of living tissues has remained a bottleneck in realizing the full potential of 3D models. Recent advances in bioprinting provide a valuable tool to fabricate biomimetic constructs, which can be applied in different stages of drug discovery research. This paper presents the first comprehensive review of bioprinting techniques applied for fabrication of 3D tissue models for pharmaceutical studies. A comparative evaluation of different bioprinting modalities is performed to assess the performance and ability of fabricating 3D tissue models for pharmaceutical use as the critical selection of bioprinting modalities indeed plays a crucial role in efficacy and toxicology testing of drugs and accelerates the drug development cycle. In addition, limitations with current tissue models are discussed thoroughly and future prospects of the role of bioprinting in pharmaceutics are provided to the reader. STATEMENT OF SIGNIFICANCE Present advances in tissue biofabrication have crucial role to play in aiding the pharmaceutical development process achieve its objectives. Advent of three-dimensional (3D) models, in particular, is viewed with immense interest by the community due to their ability to mimic in vivo hierarchical tissue architecture and heterogeneous composition. Successful realization of 3D models will not only provide greater in vitro-in vivo correlation compared to the two-dimensional (2D) models, but also eventually replace pre-clinical animal testing, which has their own shortcomings. Amongst all fabrication techniques, bioprinting- comprising all the different modalities (extrusion-, droplet- and laser-based bioprinting), is emerging as the most viable fabrication technique to create the biomimetic tissue constructs. Notwithstanding the interest in bioprinting by the pharmaceutical development researchers, it can be seen that there is a limited availability of comparative literature which can guide the proper selection of bioprinting processes and associated considerations, such as the bioink selection for a particular pharmaceutical study. Thus, this work emphasizes these aspects of bioprinting and presents them in perspective of differential requirements of different pharmaceutical studies like in vitro predictive toxicology, high-throughput screening, drug delivery and tissue-specific efficacies. Moreover, since bioprinting techniques are mostly applied in regenerative medicine and tissue engineering, a comparative analysis of similarities and differences are also expounded to help researchers make informed decisions based on contemporary literature.

Numerical Investigations of Heat Transfer Enhancement of Water-Based Al2O3 Nanofluids in a Sinusoidal-Wall Channel

This research numerically investigates the heat transfer of water-Al2O3 nanofluids in a two dimensional sinusoidal wavy channel. Simulation studies are performed for fully developed flow conditions in a channel with eight waves. The temperature of the input fluid is taken to be less than that temperature of wavy walls. The governing continuity, momentum and energy equations are numerically solved using finite volume method based on SIMPLE technique. Numerical simulations were carried out for a Reynolds number ranging from 400 to 1600 and a nanofluid volume fraction, O where 0≤O≤8%. The effect of distance between channel walls are studied by varying Hmin/Hmax ratio from 0.3 to 0.5 for keeping wave length and wave amplitude values fixed. The effect of these parameters on local and average Nusselt numbers and heat transfer enhancement are presented and discussed. The results revealed that the addition of nano-particles can increase heat transfer significantly.Copyright

Essential steps in bioprinting: From pre- to post-bioprinting

An increasing demand for directed assembly of biomaterials has inspired the development of bioprinting, which facilitates the assembling of both cellular and acellular inks into well-arranged three-dimensional (3D) structures for tissue fabrication. Although great advances have been achieved in the recent decade, there still exist issues to be addressed. Herein, a review has been systematically performed to discuss the considerations in the entire procedure of bioprinting. Though bioprinting is advancing at a rapid pace, it is seen that the whole process of obtaining tissue constructs from this technique involves multiple-stages, cutting across various technology domains. These stages can be divided into three broad categories: pre-bioprinting, bioprinting and post-bioprinting. Each stage can influence others and has a bearing on the performance of fabricated constructs. For example, in pre-bioprinting, tissue biopsy and cell expansion techniques are essential to ensure a large number of cells are available for mass organ production. Similarly, medical imaging is needed to provide high resolution designs, which can be faithfully bioprinted. In the bioprinting stage, compatibility of biomaterials is needed to be matched with solidification kinetics to ensure constructs with high cell viability and fidelity are obtained. On the other hand, there is a need to develop bioprinters, which have high degrees of freedom of movement, perform without failure concerns for several hours and are compact, and affordable. Finally, maturation of bioprinted cells are governed by conditions provided during the post-bioprinting process. This review, for the first time, puts all the bioprinting stages in perspective of the whole process of bioprinting, and analyzes their current state-of-the art. It is concluded that bioprinting community will recognize the relative importance and optimize the parameter of each stage to obtain the desired outcomes.

Bone Tissue Bioprinting for Craniofacial Reconstruction

Craniofacial (CF) tissue is an architecturally complex tissue consisting of both bone and soft tissues with significant patient specific variations. Conditions of congenital abnormalities, tumor resection surgeries, and traumatic injuries of the CF skeleton can result in major deficits of bone tissue. Despite advances in surgical reconstruction techniques, management of CF osseous deficits remains a challenge. Due its inherent versatility, bioprinting offers a promising solution to address these issues. In this review, we present and analyze the current state of bioprinting of bone tissue and highlight how these techniques may be adapted to serve regenerative therapies for CF applications. Biotechnol. Bioeng. 2017;114: 2424-2431.