3D bioprinting of collagen-based materials for oral medicine
(2023) 5:23
Yang et al. Collagen and Leather
https://doi.org/10.1186/s42825-023-00129-3
Collagen and Leather
Open Access
REVIEW
3D bioprinting of collagen‑based materials
for oral medicine
Bosen Yang1†, Hai Liu1†, Linli Jiang2, Yiwei Zeng2, Yiyuan Han3*, Chuanlu Sha1, Xin Xie1, Hui Li2*,
Jiajing Zhou1* and Wei Lin1
Abstract
Oral diseases have emerged as one of the leading public health challenges globally. Although the existing clinical
modalities for restoration of dental tissue loss and craniomaxillofacial injuries can achieve satisfactory therapeutic
results, they cannot fully restore the original complex anatomical structure and physiological function of the tissue.
3D printing of biological tissues has gained growing interest in the field of oral medicine with the ability to control
the bioink component and printing structure for spatially heterogeneous repairing constructs, holding enormous
promise for the precise treatment of oral disease. Particularly, collagen-based materials have been recognized
as promising biogenic bioinks for the regeneration of several tissues with high cell-activating and biocompatible
properties. In this review, we summarize 3D printing methods for collagen-based biomaterials and their mechanisms.
Additionally, we highlight the animal sources of collagen and their characteristics, as well as the methods of collagen extraction. Furthermore, this review provides an overview of the 3D bioprinting technology for the regeneration of the pulpal nerve and blood vessels, cartilage, and periodontal tissue. We envision that this technique opens
up immense opportunities over the conventional ones, with high replicability and customized function, which can
ultimately promote effective oral tissue regeneration.
Keywords 3D bioprinting, Oral medicine, Tissue engineering, Collagen, Scaffold materials, Bioink, Hydrogel
†
Bosen Yang and Hai Liu contributed equally to this work.
*Correspondence:
Yiyuan Han
Hui Li
Jiajing Zhou
Full list of author information is available at the end of the article
© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the
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Yang et al. Collagen and Leather
(2023) 5:23
Page 2 of 19
Graphical Abstract
1 Introduction
Oral health is important to the overall health and wellbeing of the public. According to the Global Burden
of Disease (GBD) 2015 study, nearly 3.5 billion people worldwide have suffered from pain and discomfort
associated with oral disease [1], including dental caries,
periodontal disease, craniomaxillofacial tissues damage,
etc. For example, dental caries, the most prevalent one,
caused by an ecological disorder of the dental biofilm
adhering to the surface of tooth enamel [2], can spread
to the pulp and cause infection, resulting in severe pain
[3]. Periodontal disease is a long-term inflammatory disease that affect tissues surrounding and supporting the
teeth, usually caused by trauma or bacterial infection.
The injury of periodontal tissues (e.g., gums, periodontal
ligaments, dental bone, alveolar bone and other supporting periodontal connective tissues) is a hallmark of these
diseases [4–6]. The ultimate goal of oral treatment is to
regenerate the original structure and performance of the
periodontal complex [7]. However, it is still challenging
to realize the recovery of these tissue injuries. Although
the existing clinical modalities have shown promising
therapeutic efficacy in the restoration of dental tissue loss
and craniomaxillofacial injuries, they still cannot restore
the original complex anatomical structure and physiological function of the tissue.
Three-dimensional (3D) bioprinting has attracted
immense interest in the field of biomedical engineering due to the desire for precision and customization in
tissue regeneration. This technique, first used by Charles
Hull in 1986, employed layered light-cured materials to
form a 3D structure in sequence [8]. Specifically, a digital model file is used as the basis for constructing an
object in progressive layers utilizing a bondable material master such as powdered metal or plastic. It can
directly produce components of virtually any shapes on
the basis of the computer graphics data, eliminating the
need for complicate processing, significantly shortening
product development cycles, lowering production costs,
and enhancing product functions [9]. Over the past decade, 3D bioprinting technology has been widely applied
in medical fields including regeneration medicine [10],
anatomical model construction [11], pharmaceutical formulations [12, 13]. As a result of this technology’s potential to build 3D bionic functional tissues, it has gradually
been applied to the field of dentistry to precisely target
oral tissue regeneration and repair of craniomaxillofacial
injuries. Dental surgery has evolved from a conventional,
purely empirical approach to digitalization and precision
owing to the usage of 3D printing technologies.
The first case of a large periodontal osseous defect
being treated in a human using 3D-printed technology was reported by Rasperini et al. [14]. A bioresorbable patient-specific polymer scaffold was designed with
signaling growth factor and the treated area underwent
good recovery for 12 months during the therapy. This
work revealed that 3D-printed image-based scaffolds
provide the potential for reconstruction of oral tissues.
Yang et al. Collagen and Leather
(2023) 5:23
Page 3 of 19
Fig. 1 A Collagen amino acid chain. B 3D bioprinting of collagen-based materials for oral medicine
Employing 3D bioprinting to create scaffolds, tissue analogs, and organs is an innovative solution that can help
dentists overcome some of the most pressing problems
today [15]. Some scholars have demonstrated that the
application of 3D printing technology improves operational accuracy by 36.23% and shortens the operational
time by 17.63% [16, 17]. For example, the construction
of 3D printed scaffolds that allow cell attachment, migration, and proliferation, has been exploited, particularly
for the regeneration of complex anatomical structure
(e.g., pulpodentinal complex, periodontal tissue complexes) [18–20]. The development of 3D printing te (...truncated)