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Steele, E.M.; Carr, Z.L.; Dosmar, E. Bioprinting of Hydrogel-Based Drug Delivery Systems. Encyclopedia. Available online: (accessed on 15 April 2024).
Steele EM, Carr ZL, Dosmar E. Bioprinting of Hydrogel-Based Drug Delivery Systems. Encyclopedia. Available at: Accessed April 15, 2024.
Steele, Eliza Marie, Zacheus L. Carr, Emily Dosmar. "Bioprinting of Hydrogel-Based Drug Delivery Systems" Encyclopedia, (accessed April 15, 2024).
Steele, E.M., Carr, Z.L., & Dosmar, E. (2024, February 27). Bioprinting of Hydrogel-Based Drug Delivery Systems. In Encyclopedia.
Steele, Eliza Marie, et al. "Bioprinting of Hydrogel-Based Drug Delivery Systems." Encyclopedia. Web. 27 February, 2024.
Bioprinting of Hydrogel-Based Drug Delivery Systems

Globally, thousands of people are affected by severe nerve injuries or neurodegenerative disorders. These conditions cannot always be cured because nerve tissue either does not regenerate or does so at a slow rate. Therefore, tissue engineering has emerged as a potential treatment approach. The combination of bioprinting, hydrogels, and drug delivery effectively addresses key issues in nerve tissue regeneration.

bioprinting 3D printing tissue engineering nerve tissue engineering scaffolds drug delivery

1. Introduction

Severe injuries to the human nervous system can lead to profound consequences, primarily because it shows little to no capacity for self-regeneration. Annually, there are approximately 17,000 new cases of spinal cord injury (SCI), 80,000 cases of severe traumatic brain injury (TBI), and millions of cases of neurodegenerative diseases in the U.S. [1][2][3]. Additionally, 13 to 23 out of every 1 million individuals suffer from peripheral nerve injuries, often with poor prognoses [4]. Unfortunately, prevailing treatments focus primarily on symptom management rather than on tissue regeneration [5]. However, the emerging field of tissue engineering holds promise for developing therapies that can regenerate nerve tissue and restore its functionality.
The objective of tissue engineering is to create biological materials that can replace, restore, improve, or maintain the function of damaged tissues [6]. The most effective tissue engineering strategies use the interdisciplinary triad of tissue engineering: cells, scaffolds, and biochemical/physical signals [6]. Cell sources are autologous, allogeneic, or xenogeneic, ranging from stem cells or differentiated cells [6][7], while scaffolds, constructed from either natural or synthetic biomaterials, are typically fabricated via methods such as freeze-drying, electrospinning, decellularization, or bioprinting [8]. Biochemical signals refer to growth factors or pharmaceuticals [6], while physical signals involve mechanical loading. Efforts towards nerve regeneration present unique problems due to the structural and functional complexity of neural tissues. The limited capacity for self-regeneration creates a powerful impetus for alternative interventions to address nerve damage due to injury and degenerative diseases. Bioprinting, particularly with hydrogel-based bioinks, offers a promising solution to these challenges by enabling the creation of customized, three-dimensional, biomimetic structures. These structures can also be optimized for cell growth and natural tissue integration due to the versatility of polymeric hydrogels. Additionally, by employing hydrogels, drug delivery capabilities can be introduced into bioprinted scaffolds, thereby elevating the therapeutic potential of the system. By enabling the sustained release of neurotrophic factors or specific drugs, the system transitions from passively to actively promoting nerve regeneration and functional recovery. The combination of bioprinting, hydrogels, and drug delivery effectively addresses key issues in nerve tissue regeneration. This approach creates an optimal environment for nerve repair and regeneration and holds the potential to administer precise treatments to improve the regenerative process. Consequently, this strategy not only deals with the structural and functional intricacies of nerve regeneration, but also paves the way for more effective treatment methods for a wider range of neurological disorders. 

2. Bioprinting

Three-dimensional bioprinting is an additive manufacturing process that uses cell-infused inks, called bioinks, to 3D-print complex tissue and/or organ resembling constructs [9][10]. In tissue engineering, the terms “3D printing” and “3D bioprinting” are often used interchangeably, but it is important to note their differences. Three-dimensional bioprinting uses bioinks that contain living cells and biologics to create tissues, while three-dimensional printing uses completely inert, non-living inks to create porous scaffolds to support cell attachment, proliferation, and differentiation [11]. In recent years, 3D bioprinting has rapidly grown in popularity due to its potential applications in tissue engineering and drug screening [12].
A typical bioprinting technique contains three main steps: pre-processing, processing, and post-processing [9]. Pre-processing consists of gathering imaging data, from computed tomography (CT), magnetic resonance imaging (MRI), ultrasound imaging, and/or optical microscopy [9]. The data are then transferred to computer-aided design (CAD) software to 3D-model the desired, patient-specific tissue, or create free-form models. The processing step of bioprinting includes bioink preparation and the printing process [9]. The most common bioprinting methods are described below and are summarized in Table 1 and the relative benefits and limitations are depicted in Figure 1. The post-processing phase of bioprinting includes maturing the printed tissue, typically by using a bioreactor to foster the growth and development of tissue in ideal environmental and mechanical conditions [13]. In theory, the tissue would then be ready for its desired application. In the context of neural tissue engineering, the bioprinting process is similar, with the exception that the use of bioreactors in the field has not yet been extensively studied [13].
Figure 1. A visual representation of each bioprinting method’s advantages and disadvantages. Notably, each point is plotted based on the average value for that trait; some printing methods have very variable trait characteristics, but the standard value has been selected and is shown in the plot. For example, the printing speed of the droplet-based DOD inkjet method is highly variable and depends greatly on material viscosity. The majority of the time, low material viscosities are used with DOD, which leads to fast printing speeds, which is what is depicted here.
Table 1. The five (5) bioprinting process methods, a brief description of each, and a thorough comparison analysis of benefits and limitations. Eight criteria were selected to evaluate each process. The criteria are listed in order as follows: printing speed, cell resolution, structural integrity, post-printing cell viability, cross-linking time, allowable bioink viscosity, cell density, and cost. A ninth is present for methods with additional important criteria to consider.


  1. Anonymous. Neurodegenerative Diseases. n.d. Available online: (accessed on 2 August 2023).
  2. Bennett, J.M.; Das, J.; Emmady, P.D. Spinal Cord Injuries. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2023.
  3. Anonymous. Brain Trauma Foundation—Frequently Asked Questions (FAQ). n.d. Available online: (accessed on 2 August 2023).
  4. Zhang, S.; Huang, M.; Zhi, J.; Wu, S.; Wang, Y.; Pei, F. Research Hotspots and Trends of Peripheral Nerve Injuries Based on Web of Science From 2017 to 2021: A Bibliometric Analysis. Front. Neurol. 2022, 13, 872261.
  5. Hlavac, N.; Kasper, M.; Schmidt, C.E. Progress toward finding the perfect match: Hydrogels for treatment of central nervous system injury. Mater. Today Adv. 2020, 6, 100039.
  6. Mhanna, R.; Hasan, A. Introduction to Tissue Engineering. In Tissue Engineering for Artificial Organs; Hasan, A., Ed.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2017; pp. 1–34.
  7. Anonymous. NPTEL: Biotechnology—NOC: Tissue Engineering. n.d. Available online: (accessed on 2 August 2023).
  8. Collins, M.N.; Ren, G.; Young, K.; Pina, S.; Reis, R.L.; Oliveira, J.M. Scaffold Fabrication Technologies and Structure/Function Properties in Bone Tissue Engineering. Adv. Funct. Mater. 2021, 31, 2010609.
  9. Vijayavenkataraman, S.; Yan, W.-C.; Lu, W.F.; Wang, C.-H.; Fuh, J.Y.H. 3D bioprinting of tissues and organs for regenerative medicine. Adv. Drug Deliv. Rev. 2018, 132, 296–332.
  10. Knowlton, S.; Anand, S.; Shah, T.; Tasoglu, S. Bioprinting for Neural Tissue Engineering. Trends Neurosci. 2018, 41, 31–46.
  11. Ozbolat, I.T.; Hospodiuk, M. Current advances and future perspectives in extrusion-based bioprinting. Biomaterials 2016, 76, 321–343.
  12. Anonymous. Polymers Free Full-Text 3D Bioprinting in Tissue Engineering for Medical Applications: The Classic and the Hybrid. n.d. Available online: (accessed on 28 June 2023).
  13. Wang, W.; Deng, Q.; Li, T.; Liu, Y.; Liu, Y.; Sun, Y.; Deng, C.; Zhou, X.; Ma, Z.; Qiang, L.; et al. Research Update on Bioreactors Used in Tissue Engineering. J. Shanghai Jiaotong Univ. (Sci.) 2021, 26, 272–283.
  14. Unagolla, J.M.; Jayasuriya, A.C. Hydrogel-based 3D bioprinting: A comprehensive review on cell-laden hydrogels, bioink formulations, and future perspectives. Appl. Mater. Today 2020, 18, 100479.
  15. Li, H.; Tan, C.; Li, L. Review of 3D printable hydrogels and constructs. Mater. Des. 2018, 159, 20–38.
  16. Sun, W.; Starly, B.; Daly, A.C.; Burdick, J.A.; Groll, J.; Skeldon, G.; Shu, W.; Sakai, Y.; Shinohara, M.; Nishikawa, M.; et al. The bioprinting roadmap. Biofabrication 2020, 12, 022002.
  17. Cadena, M.; Ning, L.; King, A.; Hwang, B.; Jin, L.; Serpooshan, V.; Sloan, S.A. Three Dimensional Bioprinting of Neural Tissues. Adv. Healthc. Mater. 2021, 10, e2001600.
  18. Heo, D.N.; Lee, S.-J.; Timsina, R.; Qiu, X.; Castro, N.J.; Zhang, L.G. Development of 3D printable conductive hydrogel with crystallized PEDOT:PSS for neural tissue engineering. Mater. Sci. Eng. C 2019, 99, 582–590.
  19. Groll, J.; Burdick, J.A.; Cho, D.-W.; Derby, B.; Gelinsky, M.; Heilshorn, S.C.; Jüngst, T.; Malda, J.; Mironov, V.A.; Nakayama, K.; et al. A definition of bioinks and their distinction from biomaterial inks. Biofabrication 2018, 11, 013001.
Subjects: Neurosciences
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