Current Advances in 3D Bioprinting Technology and Its Applications for Tissue Engineering

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Current Advances in 3D Bioprinting Technology and Its Applications for Tissue Engineering polymers Review Current Advances in 3D Bioprinting Technology and Its Applications for Tissue Engineering JunJie Yu 1,2, Su A Park 2 , Wan Doo Kim 2, Taeho Ha 3, Yuan-Zhu Xin 4, JunHee Lee 2,* and Donghyun Lee 1,* 1 Department of Biomedical Engineering, School of Integrative Engineering, Chung-Ang University, 221 Heukseok-Dong, Dongjak-Gu, Seoul 06974, Korea; [email protected] 2 Department of Nature-Inspired System and Application, Korea Institute of Machinery & Materials, 156 Gajeongbuk-Ro, Yuseong-Gu, Daejeon 34103, Korea; [email protected] (S.A.P.); [email protected] (W.D.K.) 3 Department of 3D Printing, Korea Institute of Machinery & Materials, 156 Gajeongbuk-Ro, Yuseong-Gu, Daejeon 34103, Korea; [email protected] 4 Department of Engineering Mechanics, School of Mechanical and Aerospace Engineering, Jilin University, No. 5988, Renmin Street, Changchun 130025, China; [email protected] * Correspondence: [email protected] (J.L.); [email protected] (D.L.) Received: 12 October 2020; Accepted: 7 December 2020; Published: 11 December 2020 Abstract: Three-dimensional (3D) bioprinting technology has emerged as a powerful biofabrication platform for tissue engineering because of its ability to engineer living cells and biomaterial-based 3D objects. Over the last few decades, droplet-based, extrusion-based, and laser-assisted bioprinters have been developed to fulfill certain requirements in terms of resolution, cell viability, cell density, etc. Simultaneously, various bio-inks based on natural–synthetic biomaterials have been developed and applied for successful tissue regeneration. To engineer more realistic artificial tissues/organs, mixtures of bio-inks with various recipes have also been developed. Taken together, this review describes the fundamental characteristics of the existing bioprinters and bio-inks that have been currently developed, followed by their advantages and disadvantages. Finally, various tissue engineering applications using 3D bioprinting are briefly introduced. Keywords: 3D bioprinter; natural polymer; synthetic polymer; bio-ink; tissue engineering 1. Introduction The goal of tissue engineering, which is based on scaffold-based approaches, is the replacement/regeneration of damaged tissues or organs. A key prerequisite for such scaffold-based approaches is that the scaffold should be biodegraded after tissue restoration. Moreover, the structural design of scaffolds is important for successful tissue regeneration because the 3D structural characteristics and physical properties of native tissues/organs can play an essential role in the biological/physiological characteristics through appropriate cell–cell and cell-matrix interactions [1]. Additionally, scaffolds offer a suitable microenvironment for cell attachment, proliferation, and migration to promote cell growth and function [2]. Conventionally, scaffolds are fabricated using solvent casting/particulate leaching [3], gas foaming [4], melt molding [5], phase separation [6], freeze-drying [7], and electrospinning [8]. Although such manual methods allow the fabrication of porous structures, these processes could not construct tailored/regular porous structures. Notably, seeding cells on scaffolds cause considerable cell loss, resulting in poor cellular performance [9]. More important, it is difficult to create heterogeneous and multicellular structures mimicking actual tissues/organs using such conventional methods. Collectively, new biofabrication methods are necessary for advanced tissue engineering. Polymers 2020, 12, 2958; doi:10.3390/polym12122958 www.mdpi.com/journal/polymers Polymers 2020, 12, x FOR PEER REVIEW 2 of 30 3D bioprinting is an attractive biofabrication method because it enables the precise deposition of various cells/biomaterials onto predefined locations [10–12]. Additionally, it offers several advantages when compared with conventional methods. For example, this automated technique facilitates both mass production and high-throughput production with high-resolution [13]. Furthermore, customized structures for patients can be printed through computer-aided design modeling. Moreover, 3D bioprinted regular and porous structures can provide superior interconnectivity for cell growth/function. These advantages could lead to better tissue and organ regeneration (Figure 1a). PolymersMoreover,2020 many, 12, 2958 outcomes have been published annually based on 3D bioprinting (Figure 1b). 2 of 30 Considering the working principles of tissue engineering, bioprinting techniques can be categorized into four modules: (1) droplet-based, (2) extrusion-based, (3) laser-assisted, and (4) stereolithography3D bioprinting techniques. is an attractive For biofabricationthe fabrication method of an ideal because 3D itbiomimetic enables the structure precise deposition using such of variousprinting cells modules,/biomaterials bio-inks onto should predefined be carefully locations selected. [10–12]. Additionally,To be used itas o ffaers source several of advantagesa bio-ink, whenbiomaterials compared should with meet conventional the following methods. requirements: For example, (1) biocom thispatibility, automated (2) techniquebiodegradability, facilitates (3) bioprintability,both mass production and (4) andstructural high-throughput integrity after production printing with [14, high-resolution15]. To satisfy such [13]. requirements, Furthermore, variouscustomized bio-inks structures have been for patientsformulated can by be considering printed through their mechanical computer-aided properties; design in particular, modeling. mixturesMoreover, of 3D different bioprinted biomaterials regular and have porous attracted structures attention can as provide potential superior bio-ink interconnectivity sources. for cell growthOver/function. the past Thesedecade, advantages research on could the use lead of two to better or more tissue bio- andinks organthat combine regeneration cells has (Figure garnered1a). greatMoreover, interest many in the outcomes regeneration have beenof artificial published tissues. annually Various based types on of 3D cells bioprinting have been (Figure used in1 b).mixtures of differentConsidering bio-inks the to workingachieve remarkably principles successful of tissue results engineering, in the repair bioprinting of bone, techniques cartilage, trachea, can be bloodcategorized vessels, into and four liver modules: tissue. Although (1) droplet-based, several studies (2) related extrusion-based, to 3D bioprinting (3) laser-assisted, have been reported, and (4) thestereolithography objective of this techniques. review is Forto provide the fabrication useful ofinformation an ideal 3D regarding biomimetic the structurecurrent state using of such 3D printingbioprinting modules, techniques bio-inks and should bio-inks. be carefully Moreover, selected. based To on be each used asbio a- sourceink characteristic, of a bio-ink, biomaterialswe propose blendsshould of meet two the or following more bio requirements:-inks for use in (1) various biocompatibility, tissue engineering (2) biodegradability, applications. (3) Notably, bioprintability, in this review,and (4) we structural provide integrity insights afterinto the printing combination [14,15]. formulas To satisfy of suchbio-inks, requirements, cell types, variouscell density, bio-inks and crosslinkers,have been formulated which are by major considering challenges their mechanicalfor building properties; successful in structures. particular, mixturesFinally, the of dicurrentfferent limitationsbiomaterials and have future attracted prospects attention are discussed. as potential bio-ink sources. Figure 1. (a) Numerous applications of tissue engineering and ( b) the number of publications based on 3D bioprinting. The image ( a) was adapted with permission from [[16]16].. Copyright 2018 E Elsevier;lsevier; iillustrationllustration of the (b) waswas usingusing searchsearch thethe termsterms ofof “3D“3D bioprinting”.bioprinting”. Data analysis was searched Pubmed and Scopus system on 11 November 2020. 2. 3DOver Bioprinters the past for decade, Tissue research Engineering on the use of two or more bio-inks that combine cells has garnered great interest in the regeneration of artificial tissues. Various types of cells have been used in mixtures of diffAserent mentioned bio-inks previously, to achieve remarkably3D bioprinters successful can be commonly results in theclassified repair ofinto bone, four cartilage, groups based trachea, on theirblood working vessels, andprinciples. liver tissue. In this Although section, severalwe introduced studies relatedseven types to 3D of bioprinting bioprinters: have (1) been inkjet reported,-based, (the2) objectiveextrusion of-based, this review (3) laser is to-assisted, provide useful(4) stereolithography, information regarding (5) acoustic, the current (6) state microvalve, of 3D bioprinting and (7) needletechniques array and bioprinters bio-inks. Moreover,(Figure 2). basedWe also on eachprovi bio-inkde a brief characteristic, overview of we the propose working blends principles of two orof eachmore printing bio-inks module for use inand various its fundamental tissue engineering characteristics. applications. The type Notably, of bioprinter in this should review, be we carefully provide selectedinsights intobased the on combination the structural formulas properties of bio-inks, of the targeted cell types, tissues/organs. cell density, and crosslinkers, which are major challenges for building successful structures. Finally, the current limitations and future prospects
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