Smart Bioinks for the Printing of Human Tissue Models

3D bioprinting has tremendous potential to revolutionize the field of regenerative medicine by automating the process of tissue engineering. A significant number of new and advanced bioprinting technologies have been developed in recent years, enabling the generation of increasingly accurate models of human tissues both in the healthy and diseased state. Accordingly, this technology has generated a demand for smart bioinks that can enable the rapid and efficient generation of human bioprinted tissues that accurately recapitulate the properties of the same tissue found in vivo. Here, we define smart bioinks as those that provide controlled release of factors in response to stimuli or combine multiple materials to yield novel properties for the bioprinting of human tissues. This perspective piece reviews the existing literature and examines the potential for the incorporation of micro and nanotechnologies into bioinks to enhance their properties. It also discusses avenues for future work in this cutting-edge field.

Download Full-text

3D Printing Breast Tissue Models: A Review of Past Work and Directions for Future Work

Micromachines ◽

10.3390/mi10080501 ◽

2019 ◽

Vol 10 (8) ◽

pp. 501 ◽

Cited By ~ 7

Author(s):

Chantell Cleversey ◽

Meghan Robinson ◽

Stephanie M. Willerth

Keyword(s):

Tissue Engineering ◽

Breast Tissue ◽

In Vitro Models ◽

Attractive Potential ◽

Biomaterial Scaffolds ◽

Potential Alternative ◽

Future Work ◽

Tissue Models

Breast cancer often results in the removal of the breast, creating a need for replacement tissue. Tissue engineering offers the promise of generating such replacements by combining cells with biomaterial scaffolds and serves as an attractive potential alternative to current surgical repair methods. Such engineered tissues can also serve as important tools for drug screening and provide in vitro models for analysis. 3D bioprinting serves as an exciting technology with significant implications and applications in the field of tissue engineering. Here we review the work that has been undertaken in hopes of generating the recognized in-demand replacement breast tissue using different types of bioprinting. We then offer suggestions for future work needed to advance this field for both in vitro and in vivo applications.

Download Full-text

Of balls, inks and cages: Hybrid biofabrication of 3D tissue analogs

International Journal of Bioprinting ◽

10.18063/ijb.v5i1.167 ◽

2018 ◽

Vol 5 (1) ◽

Cited By ~ 1

Author(s):

Nicanor Moldovan ◽

Leni Maldovan ◽

Michael Raghunath

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

Hybrid Approach ◽

Three Dimensional ◽

3D Bioprinting ◽

Support Structures ◽

Cell Clusters ◽

3D Space ◽

Technical Solutions

The overarching principle of three-dimensional (3D) bioprinting is the placing of cells or cell clusters in the 3D space to generate a cohesive tissue microarchitecture that comes close to in vivo characteristics. To achieve this goal, several technical solutions are available, generating considerable combinatorial bandwidth: (i) Support structures are generated first, and cells are seeded subsequently; (ii) alternatively, cells are delivered in a printing medium, so-called “bioink,” that contains them during the printing process and ensures shape fidelity of the generated structure; and (iii) a “scaffold-free” version of bioprinting, where only cells are used and the extracellular matrix is produced by the cells themselves, also recently entered a phase of accelerated development and successful applications. However, the scaffold-free approaches may still benefit from secondary incorporation of scaffolding materials, thus expanding their versatility. Reversibly, the bioink-based bioprinting could also be improved by adopting some of the principles and practices of scaffold-free biofabrication. Collectively, we anticipate that combinations of these complementary methods in a “hybrid” approach, rather than their development in separate technological niches, will largely increase their efficiency and applicability in tissue engineering.

Download Full-text

3D Bioprinting of Human Tissues: Biofabrication, Bioinks and Bioreactors

International Journal of Molecular Sciences ◽

10.3390/ijms22083971 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3971

Author(s):

Jianhua Zhang ◽

Esther Wehrle ◽

Marina Rubert ◽

Ralph Müller

Keyword(s):

Tissue Engineering ◽

Human Tissue ◽

Fluid Shear Stress ◽

Pharmaceutical Research ◽

Three Dimensional ◽

Biological Tissues ◽

Layer By Layer ◽

Human Tissues ◽

3D Bioprinting

The field of tissue engineering has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes for regenerative medicine and pharmaceutical research. Conventional scaffold-based approaches are limited in their capacity to produce constructs with the functionality and complexity of native tissue. Three-dimensional (3D) bioprinting offers exciting prospects for scaffolds fabrication, as it allows precise placement of cells, biochemical factors, and biomaterials in a layer-by-layer process. Compared with traditional scaffold fabrication approaches, 3D bioprinting is better to mimic the complex microstructures of biological tissues and accurately control the distribution of cells. Here, we describe recent technological advances in bio-fabrication focusing on 3D bioprinting processes for tissue engineering from data processing to bioprinting, mainly inkjet, laser, and extrusion-based technique. We then review the associated bioink formulation for 3D bioprinting of human tissues, including biomaterials, cells, and growth factors selection. The key bioink properties for successful bioprinting of human tissue were summarized. After bioprinting, the cells are generally devoid of any exposure to fluid mechanical cues, such as fluid shear stress, tension, and compression, which are crucial for tissue development and function in health and disease. The bioreactor can serve as a simulator to aid in the development of engineering human tissues from in vitro maturation of 3D cell-laden scaffolds. We then describe some of the most common bioreactors found in the engineering of several functional tissues, such as bone, cartilage, and cardiovascular applications. In the end, we conclude with a brief insight into present limitations and future developments on the application of 3D bioprinting and bioreactor systems for engineering human tissue.

Download Full-text

Applications of 3D Bioprinting in Tissue Engineering and Regenerative Medicine

Journal of Clinical Medicine ◽

10.3390/jcm10214966 ◽

2021 ◽

Vol 10 (21) ◽

pp. 4966

Author(s):

Gia Saini ◽

Nicole Segaran ◽

Joseph L. Mayer ◽

Aman Saini ◽

Hassan Albadawi ◽

...

Keyword(s):

Tissue Engineering ◽

3D Printing ◽

Regenerative Medicine ◽

Living Cells ◽

Clinical Applications ◽

3D Bioprinting ◽

Future Directions ◽

Specialized Tissue ◽

Tissue Models ◽

Functional Components

Regenerative medicine is an emerging field that centers on the restoration and regeneration of functional components of damaged tissue. Tissue engineering is an application of regenerative medicine and seeks to create functional tissue components and whole organs. Using 3D printing technologies, native tissue mimics can be created utilizing biomaterials and living cells. Recently, regenerative medicine has begun to employ 3D bioprinting methods to create highly specialized tissue models to improve upon conventional tissue engineering methods. Here, we review the use of 3D bioprinting in the advancement of tissue engineering by describing the process of 3D bioprinting and its advantages over other tissue engineering methods. Materials and techniques in bioprinting are also reviewed, in addition to future clinical applications, challenges, and future directions of the field.

Download Full-text

The Arrival of Commercial Bioprinters - Towards 3D Bioprinting Revolution!

International Journal of Bioprinting ◽

10.18063/ijb.v4i2.139 ◽

2018 ◽

Vol 4 (2) ◽

Cited By ~ 24

Author(s):

Deepak Choudhury ◽

Shivesh Anand ◽

May Win Naing

Keyword(s):

Tissue Engineering ◽

Biological Research ◽

3D Bioprinting ◽

Research Groups ◽

Design Considerations ◽

The Past ◽

Early Adoption ◽

The Individual ◽

Tissue Models

The dawn of commercial bioprinting is rapidly advancing the tissue engineering field. In the past few years, new bioprinting approaches as well as novel bioinks formulations have emerged, enabling biological research groups to demonstrate the use of such technology to fabricate functional and relevant tissue models. In recent years, several companies have launched bioprinters pushing for early adoption and democratisation of bioprinting. This article reviews the progress in commercial bioprinting since the inception, with a particular focus on the comparison of different available printing technologies and important features of the individual technologies as well as various existing applications. Various challenges and potential design considerations for next generations of bioprinters are also discussed.

Download Full-text

3D Bioprinting of Vascularized Tissues for in vitro and in vivo Applications

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.664188 ◽

2021 ◽

Vol 9 ◽

Author(s):

Earnest P. Chen ◽

Zeren Toksoy ◽

Bruce A. Davis ◽

John P. Geibel

Keyword(s):

Tissue Engineering ◽

Drug Testing ◽

Rapid Development ◽

Three Dimensional ◽

3D Bioprinting ◽

Vascular Networks ◽

Main Challenge ◽

3D Printed

With a limited supply of organ donors and available organs for transplantation, the aim of tissue engineering with three-dimensional (3D) bioprinting technology is to construct fully functional and viable tissue and organ replacements for various clinical applications. 3D bioprinting allows for the customization of complex tissue architecture with numerous combinations of materials and printing methods to build different tissue types, and eventually fully functional replacement organs. The main challenge of maintaining 3D printed tissue viability is the inclusion of complex vascular networks for nutrient transport and waste disposal. Rapid development and discoveries in recent years have taken huge strides toward perfecting the incorporation of vascular networks in 3D printed tissue and organs. In this review, we will discuss the latest advancements in fabricating vascularized tissue and organs including novel strategies and materials, and their applications. Our discussion will begin with the exploration of printing vasculature, progress through the current statuses of bioprinting tissue/organoids from bone to muscles to organs, and conclude with relevant applications for in vitro models and drug testing. We will also explore and discuss the current limitations of vascularized tissue engineering and some of the promising future directions this technology may bring.

Download Full-text

3D bioprinting of stem cells and polymer/bioactive glass composite scaffolds for tissue engineering

International Journal of Bioprinting ◽

10.18063/ijb.2017.01.005 ◽

2017 ◽

Vol 3 (1) ◽

Cited By ~ 48

Author(s):

Caroline Murphy ◽

Krishna Kolan ◽

Wenbin Li ◽

Julie Semon ◽

Delbert Day ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Bioactive Glass ◽

Borate Glass ◽

Three Dimensional ◽

3D Bioprinting ◽

Glass Composite ◽

Dynamic Interactions ◽

Synthetic Scaffolds

A major limitation of using synthetic scaffolds in tissue engineering applications is insufficient angiogenesis in scaffold interior. Bioactive borate glasses have been shown to promote angiogenesis. There is a need to investigate the biofabrication of polymer composites by incorporating borate glass to increase the angiogenic capacity of the fabricated scaffolds. In this study, we investigated the bioprinting of human adipose stem cells (ASCs) with a polycaprolactone (PCL)/bioactive borate glass composite. Borate glass at the concentration of 10 to 50 weight %, was added to a mixture of PCL and organic solvent to make an extrudable paste. ASCs suspended in Matrigel were ejected as droplets using a second syringe. Scaffolds measuring 10x10x1 mm3 in overall dimensions with pore sizes ranging from 100 – 300 µm were fabricated. Degradation of the scaffolds in cell culture medium showed a controlled release of bioactive glass for up to two weeks. The viability of ASCs printed on the scaffold was investigated during the same time period. This 3D bioprinting method shows a high potential to create a bioactive, highly angiogenic three-dimensional environment required for complex and dynamic interactions that govern the cell’s behavior in vivo.

Download Full-text

Three-Dimensional Bioprinting of Articular Cartilage: A Systematic Review

Cartilage ◽

10.1177/1947603518809410 ◽

2018 ◽

Vol 12 (1) ◽

pp. 76-92 ◽

Cited By ~ 12

Author(s):

Yang Wu ◽

Patrick Kennedy ◽

Nicholas Bonazza ◽

Yin Yu ◽

Aman Dhawan ◽

...

Keyword(s):

Systematic Review ◽

Tissue Engineering ◽

Articular Cartilage ◽

Unmet Need ◽

Cell Types ◽

Living Cells ◽

Published Data ◽

3D Bioprinting ◽

Engineering Strategy

Objective Treatment of chondral injury is clinically challenging. Available chondral repair/regeneration techniques have significant shortcomings. A viable and durable tissue engineering strategy for articular cartilage repair remains an unmet need. Our objective was to systematically evaluate the published data on bioprinted articular cartilage with regards to scaffold-based, scaffold-free and in situ cartilage bioprinting. Design We performed a systematic review of studies using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and ScienceDirect databases were searched and all articles evaluating the use of 3-dimensional (3D) bioprinting in articular cartilage were included. Inclusion criteria included studies written in or translated to English, published in a peer-reviewed journal, and specifically discussing bioinks and/or bioprinting of living cells related to articular cartilage applications. Review papers, articles in a foreign language, and studies not involving bioprinting of living cells related to articular cartilage applications were excluded. Results Twenty-seven studies for articular cartilage bioprinting were identified that met inclusion and exclusion criteria. The technologies, materials, cell types used in these studies, and the biological and physical properties of the created constructs have been demonstrated. Conclusion These 27 studies have demonstrated 3D bioprinting of articular cartilage to be a tissue engineering strategy that has tremendous potential translational value. The unique abilities of the varied techniques allow replication of mechanical properties and advances toward zonal differentiation. This review demonstrates that bioprinting has great capacity for clinical cartilage reconstruction and future in vivo implantation.

Download Full-text

3D Bioprinting-Based Vascularized Tissue Models Mimicking Tissue-Specific Architecture and Pathophysiology for in vitro Studies

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.685507 ◽

2021 ◽

Vol 9 ◽

Author(s):

Dong Gyu Hwang ◽

Yoo-mi Choi ◽

Jinah Jang

Keyword(s):

Cell Cultures ◽

Disease Modeling ◽

Structural Similarity ◽

Chemical Substance ◽

Experimental Models ◽

Model Organisms ◽

3D Bioprinting ◽

Tissue Models

A wide variety of experimental models including 2D cell cultures, model organisms, and 3D in vitro models have been developed to understand pathophysiological phenomena and assess the safety and efficacy of potential therapeutics. In this sense, 3D in vitro models are an intermediate between 2D cell cultures and animal models, as they adequately reproduce 3D microenvironments and human physiology while also being controllable and reproducible. Particularly, recent advances in 3D in vitro biomimicry models, which can produce complex cell structures, shapes, and arrangements, can more similarly reflect in vivo conditions than 2D cell culture. Based on this, 3D bioprinting technology, which enables to place the desired materials in the desired locations, has been introduced to fabricate tissue models with high structural similarity to the native tissues. Therefore, this review discusses the recent developments in this field and the key features of various types of 3D-bioprinted tissues, particularly those associated with blood vessels or highly vascularized organs, such as the heart, liver, and kidney. Moreover, this review also summarizes the current state of the three categories: (1) chemical substance treatment, (2) 3D bioprinting of lesions, and (3) recapitulation of tumor microenvironments (TME) of 3D bioprinting-based disease models according to their disease modeling approach. Finally, we propose the future directions of 3D bioprinting approaches for the creation of more advanced in vitro biomimetic 3D tissues, as well as the translation of 3D bioprinted tissue models to clinical applications.

Download Full-text