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International Journal of Bioprinting                      3D bioprinting of ultrashort peptides for chondrogenesis



            1. Introduction                                    conducted layer-by-layer with the nozzle suspended above
                                                               the print and carried along a set platform. This approach
            Hydrogels are a class of materials composed of hydrophilic   allows the extrusion of bioinks with high cell density,
            networks of crosslinked polymers, which can be used to   which  makes  them  preferred  candidates  for  cellular  3D
                                                   [1]
            mimic the extracellular matrix (ECM) of the body . These   bioprinting. It is also cost-effective and easily customizable.
            materials have been used in tissue engineering for various   However, its main tradeoff is its limitations in resolution
            applications, including  chondrogenic engineering. They   and speed .
                                                                       [15]
            can create a three-dimensional (3D) structure to support
            the growth of cells and can be used to deliver drugs and   Another procedure is material jetting, which uses
            other therapeutic agents . A variety of natural and   an inkjet technique for 3D-bioprinting desired objects.
                                 [2]
            synthetic hydrogels,  including collagen, polyacrylamide,   It involves droplet formation through piezo-electric or
            and hyaluronic acid-based hydrogels, have been used in   thermally induced bubbles and downstream ejection
            chondrogenic  engineering.  However,  one  of the  main   created by a volumetric change upstream of the nozzle [16-20] .
            disadvantages of natural hydrogels, such as collagen and   Its high printing speeds, cost-effectiveness, and contactless
            hyaluronic acid, is their limited mechanical strength,   method that reduces contamination risks make it a viable
            which can limit their use in specific applications .   3D bioprinting approach. However, the fact that it is more
                                                        [3]
            Moreover,  the  synthetic  polyacrylamide  hydrogel  are   suitable for highly viscous bioinks makes it less possible
            poorly biocompatible, very costly, and difficult to work   for cellular 3D bioprinting . Hence, extrusion-based
                                                                                      [15]
            with [4,5] .                                       approaches are preferred for the creation of cell-laden
               On the other hand, ultrashort peptide hydrogels have   bioprinted structures.
            gained  recognition  recently,  particularly  for  biomedical   The final technique for 3D bioprinting is vat
            applications and tissue engineering . These ultrashort   photopolymerization. It includes several approaches, such
                                          [6]
            peptide hydrogels possess a range of properties that make   as stereolithography (SLA) and digital light processing
            them particularly attractive for tissue engineering and   (DLP) . The primary approach comprises solidifying
                                                                    [14]
            regenerative  medicine  applications.  For  example,  they   a photo-initiated liquid material using a laser or LCD
            are biocompatible, biodegradable, and nontoxic, and   light source. A platform upon which the liquid is set, is
            have the spontaneous ability to rapidly form a hydrogel   continuously raised after the light source hardens each
            at  concentrations  as  low  as  0.01%  under  physiological   layer, thus creating a high-resolution print structure . In
                                                                                                         [21]
            conditions . Furthermore, these ultrashort peptide   SLA, the laser is directed at specific solidification points to
                    [6]
            hydrogels can be designed to have a range of mechanical   form layers. On the other hand, in DLP, the laser is directed
            properties, such as stiffness, elasticity, and strength, making   at the entire surface, and the use of a mask between it and
            them highly suitable for use in various tissue engineering   the liquid achieves solidification of the desired regions.
            applications .                                     Intuitively, this approach offers very high resolution but
                     [6]
               Chondrogenic engineering is a rapidly growing field of   does not allow the incorporation of cells during the 3D
            biotechnology that focuses on using stem cells and other   bioprinting process, making it challenging to incorporate
                                                                                          [21]
            cell types to create new tissues and organs . It is a complex   high cell densities into a construct .
                                             [7]
            and challenging field of research since it requires the   Different 3D bioprinting materials have been used
            development of effective and safe methods for delivering   to fabricate cartilage constructs. Xue  et al. tested the
            therapeutic agents to the target tissue, controlling the   possibility of culturing cartilage precursor cells with
            growth  and  differentiation  of  the  engineered  cells,  and   poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) to
            ensuring that the engineered cells can integrate into the   manufacture tissue-engineered cartilage . Another group
                                                                                               [22]
            existing tissue and function properly . Recent studies have   reported the creation of cartilage constructs using collagen
                                         [8]
            demonstrated that 3D bioprinting may be a promising   hydrogels and human mesenchymal stromal cells (MSCs) .
                                                                                                           [23]
            in situ cartilage regeneration strategy [9-12] . 3D bioprinting   However, one of the main disadvantages of PHBV is its
            has provided an avenue for the regeneration of functional   relatively high cost. Additionally, the production process
            cartilage in many applications .
                                    [13]
                                                               for  PHBV  is  more  complex  and  energy-intensive  than
               3D bioprinting techniques are mainly divided into   other thermoplastics, further increasing the cost . On
                                                                                                       [24]
            three main categories: material extrusion, material jetting,   the other hand, collagen is a protein that is sensitive to
            and vat polymerization . The most widely used technique   temperature and pH changes, which can cause it to degrade
                              [14]
            is  extrusion-based  printing,  involving  the  extrusion   over time. This could result in a reduction of the structural
            of biomaterials from nozzles using either mechanical   integrity of the printed construct, making it difficult to
            or  pressure-based pumping  systems. The  extrusion is   maintain its  shape and form. Additionally, collagen is

            Volume 9 Issue 4 (2023)                         63                         https://doi.org/10.18063/ijb.719
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