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3D Printing of Hybrid-Hydrogel Materials for Tissue Engineering: a Critical Review



Key natural polymers, known as hydrogels, are an important group of materials in the design of tissue-engineered constructs that can provide a suitable habitat for cell attachment and proliferation. However, in comparison to tissues within the body, these hydrogels display poor mechanical properties. Such properties cause challenges in 3D printing of hydrogel scaffolds as well as their surgical handling after fabrication. For this reason, the purpose of this study is to critically review the 3D printing processes of hydrogels and their characteristics for tissue engineering application.


A search of Google Scholar and PubMed has been performed from 2003 to February 2022 using a combination of keywords. A review of the types of 3D printing is presented. Additionally, different types of hydrogels and nano-biocomposite materials for 3D printing application are critically reviewed. The rheological properties and crosslinking mechanisms for the hydrogels are assessed.


Extrusion-based 3D printing is the most common practice for constructing hydrogel-based scaffolds, and it allows for the use of varying types of polymers to enhance the properties and printability of the hydrogel-based scaffolds. Rheology has been found to be exceedingly important in the 3D printing process; however, shear-thinning and thixotropic characteristics should also be present in the hydrogel. Despite these features of extrusion-based 3D printing, there are limitations to its printing resolution and scale.


Combining natural and synthetic polymers and a variety of nanomaterials, such as metal, metal oxide, non-metal, and polymeric, can enhance the properties of hydrogel and provide additional functionality to their 3D-printed constructs.

Lay Summary

Essential natural materials, known as hydrogels, are important for the design of tissue-engineered constructs that allow for cells to attach and grow while receiving the nutrients necessary for growth as well. However, in comparison to the cells in the body, the hydrogels have poor functional properties. Because of this, the purpose of this study is to assess the 3D printing processes of the hydrogels, and the appropriate characteristics of the hydrogels that allow this material to be useful in tissue engineering processes. A review of the types of 3D printing is presented, and the different types of materials used for 3D printing are also assessed. Lastly, the properties of hydrogels that make them ideal for 3D printing are reviewed. The most common type of 3D printing is extrusion-based 3D printing. It allows for the use of different types of natural materials to enhance the properties and printing ability for the hydrogel-based cellular environment. The flow of a material is found to be important in 3D printing as well as the consistency and capability of a material. However, there are challenges to the 3D printing quality and size for extrusion-based 3D printing. Overall, different 3D printing techniques should be created to enhance the construction capabilities of 3D printing to meet the most favorable environment for cellular growth and attachment.

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Part of the research reported in this paper was supported by National Institute of Dental & Craniofacial Research of the National Institutes of Health under award number R15DE027533, R56DE029191, and 3R15DE027533-01A1W1.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Tajik, S., Garcia, C.N., Gillooley, S. et al. 3D Printing of Hybrid-Hydrogel Materials for Tissue Engineering: a Critical Review. Regen. Eng. Transl. Med. (2022).

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  • 3D printing
  • Hydrogel scaffold
  • Tissue engineering
  • Hybrid-hydrogel materials
  • Hydrogel 3D printing