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Engineering Science in
            Additive Manufacturing                                                TwinPrint: Dual-arm robotic bioprinting



            1. Introduction                                    exist.  Primarily,  large-scale  printing  has  not  yet  been
                                                               realized. Clinically practical sizes need to be achieved
            Three-dimensional (3D) bioprinting technology has   without extending fabrication time.  This requires an
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            facilitated remarkable advancements in the biofabrication   array of new approaches such as concurrent printing,
                                    1,2
            of complex biomimetic tissues,  thus catering to challenges   robotic maneuverability, and full system integration and
            in organ donor shortage and enabling solutions in   automation.
            personalized medicine to reduce immune system response.
            The most demanding applications for engineered tissues   Of note, a vast majority of 3D bioprinting systems
                                                  6
                              3
                                   4,5
            include the cartilage,  skin,  cardiac tissue,  vascular   involve pre-mixing or post-printing curing protocols, i.e.,
            grafts,  and hard tissues such as bones.  It has also shown   bioinks are pre-mixed before loading in a pressure-based
                 7
                                           8
            high potential in eliminating dependency on animal   extruder, and final crosslinking occurs through curing
            testing by introducing artificially constructed organs for   processes after printing. This approach, while common, is
            pharmacology and pharmaceutical research. 9        not as biologically suitable on the grand scale, due to its
                                                               dependency on ultraviolet-based or chemical crosslinking
              The heterogeneity and complexity of human tissues
            necessitate 3D  bioprinting  of multi-material and multi-  techniques. Soft matter bioinks, such as ultrashort self-
            cellular constructs with physical and mechanical properties   assembling peptides, are key candidates to explore for 3D
            closer to native tissues.  This entails the integration of   bioprinting due to their instantaneous gelation properties,
                               10
            various  biomaterials and  cell  types  to fabricate  a single   biocompatibility, and nanofibrous topography resembling
                                                                                         17,18,22
            biomimetic construct. 11,12  In light of this, several researchers   the natural extracellular matrix.   While avoiding the
            have proposed methods to accomplish the goal of 3D   use of harmful crosslinking reagents, their instantaneous
            printing multi-material acellular and cellular scaffolds of   binding nature requires increased precision control.
            varying mechanical properties and print resolutions. Some   Screw-driven syringe pump extrusion systems have been
            have modified the design of commercial, conventional   found to offer better control and flow accuracy when
                                                                                         9,23
            3D printers by integrating multiple printheads for multi-  working with ultrashort peptides.  Our previous research
            material 3D bioprinting. 11,13  On the other hand, Liu   explored the development of microfluidic syringe pump
            et al.  and Miri et al.  developed their own multi-head 3D   extrusion systems embedded with dual coaxial nozzles to
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                14
            bioprinter with a rapid switching mechanism for bioink   accommodate the gelation nature of peptide bioink. 20,23-25
            interchangeability. A handheld multi-material 3D printer   Examining  the  use  of  articulated  robots  for  3D
            was introduced by Pagan et al.  for in situ 3D bioprinting   biofabrication applications highlights a number of
                                    16
            for tissue repair applications.                    advantages.  In comparison to traditional Cartesian 3D
              Ultrashort self-assembling amphiphilic peptides are   bioprinters, articulated robot workspace is not confined and
            compounds with both hydrophobic and hydrophilic    can perform successful in situ bioprinting at regions such
            regions. 17,18  Peptide Ac-Ile-Val-Cha-Lys-NH  (IVZK),   as curved or irregular anatomical sites, 26-28  and perform
                                                 2
            which  was  investigated in  this  study  for  its  suitable   additional tasks aside from 3D bioprinting, making them
            properties belongs to a class of tetrameric ultrashort   cost-effective. More significantly, articulated robots offer
            self-assembling peptides that was described in detail in   additional degrees of freedom, which allows for faster
            earlier  publications. 19,20  These peptides assemble into   fabrication time of highly curved scaffolds with intricate
            fibers and further into 3D supramolecular structures in   geometry while achieving high deposition precision and
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            the form of hydrogels by non-covalent interactions, such   printing resolution.  Non-planar robotic printing can
            as van der Waals interactions and hydrogen bonding.   revolutionize 3D bioprinting by breaking away from the
            Adding ionic solutions such as phosphate-buffered saline   traditional layer-by-layer XYZ approach and creating more
            (PBS) to aqueous peptide solutions can accelerate their   defined extrusion paths to fabricate complex organs and
            fiber formation, reducing gelation times to minutes and   tissues. 30-32  A multi-arm configuration running in tandem
            seconds, depending on the specific peptide sequence and   reduced biofabrication time considerably by increasing the
            the peptide concentration. These properties underscore   degrees of freedom from the standard 3 axes to 5–6 axes,
            the potential of ultrashort self-assembling amphiphilic   which would be vital for in situ bioprinting at the clinical
            peptides as an optimal bioink material in extrusion-based   phase. 33
            3D printing and bioprinting, as alternatives to gelatin and   Among many challenges facing 3D bioprinting, one
            alginate-based bioinks, to facilitate instantaneous layer-by-  significant obstacle is achieving reliability and robustness.
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            layer printing of acellular and cell-laden material.  Currently, 3D bioprinting is hindered by extrusion
              With several promising attempts at developing    failures, bioink incompatible mechanical and rheological
            multi-material  3D  bioprinters,  certain  challenges  still   properties, and the lack of robust, end-to-end automation.


            Volume 1 Issue 4 (2025)                         2                          doi: 10.36922/ESAM025410025
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