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International Journal of Bioprinting In situ bioprinting for cartilage repair

matches the defect. More importantly, due to the uncertain to the force generated by the high-speed movement of the
parameters associated with in vitro culturing, the in situ printing head, leading to scaffold formation failure.
approach provides the natural microenvironment for The reconstruction of cartilage defects is a significant
cell growth, proliferation, and differentiation, which can part of in situ bioprinting. Inspired by the traditional
promote tissue regeneration. 35,36 To this end, an in situ surgical procedure, the assessment of cartilage defects
bioprinting device was developed for efficient cartilage in current clinical practice is mostly based on MRI
repair. examinations, while the analysis of color images of cartilage

It costs about RMB1500 to build a custom-made defects is rarely performed. 41,42 In addition, there are limited
manipulator (details for each component can be found corresponding image analysis methods for defects that
in the Table S1). In the articulated manipulator, the joints are discovered during the operation and have never been
are connected consecutively to each other, resulting in detected in the pre-operative examinations. Due to the
a longer transmission chain. Without a proper control simple environment during surgery and the distinct color
method, the long transmission chain may lead to a more difference between healthy and injured cartilage (healthy =
severe transmission error, since the wrong movement white; injured = red), the grayscale distribution of defects
of a joint will affect the adjacent ones. Due to the has apparent bimodal distribution characteristics. Based on
longer transmission chain, the positional accuracy of the grayscale histogram, a defect can be segmented using
the articulated manipulator is poor. Different from the threshold determined by the bimodal method.
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the articulated manipulator, the actuators in a parallel Furthermore, the biocompatibility of the printed
manipulator are connected directly with the base and the scaffold was evaluated. The overall viability of cells in the
end effector, making it more rigid and stable. Due to its printed scaffold was higher than 85%, and there was no
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high rigidity and stability, the parallel manipulator has statistically significant difference between the experimental
higher accuracy and quicker responses. Therefore, in and control groups, indicating that the scaffold was non-
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order to achieve efficient in situ cartilage repair, a parallel toxic for the cells. The proliferation experiment and live/
manipulator was utilized in the present study.
dead staining results further confirmed that the printed
As for the direct-writing bioprinting technology, the scaffold was beneficial to cell growth and could be used in
uniformity of the extruded filament is related not only to animal experiments. In vivo experiments were conducted
the rheological properties of the material, but also to the to determine whether in situ bioprinting is beneficial to
printing process. On the premise that the material is cartilage repair. In the present study, we utilized a bioink
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printable, the printing parameters, i.e., the moving speed of comprising HAMA, CSMA, and GelMA, which have been
the printing head and the extrusion speed of the material, shown to play an important role in chondrocyte survival
have an overall impact on the quality of the printed and phenotypic maintenance. 43,44 More specifically,
scaffold. In this study, optimization of the aforementioned hyaluronic acid is an important component of the synovial
parameters was achieved by adjusting the printing speed fluid, which acts as lubricant in the joint cartilage to
and extrusion multiplier in the slicing software. The absorb shocks. Hyaluronic acid provides stimulus for
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experiments revealed that the extrusion multiplier plays chondrogenesis, promotes ECM deposition, and restrains
a major role in the success of printing, while the printing the inflamed macrophages, thus promoting cartilage
speed affects the quality of the printed scaffold. More repair. 46,47 Chondroitin sulfate contributes to cartilage
specifically, when the multiplier was high, the filament regeneration by diminishing inflammation, regulating
accumulated together under both high and low speeds due metabolism, and absorbing water or nutrients. 48-51
to over-extrusion, resulting in no macroscopic pores in the Compared to the direct implantation group, the in situ
scaffold. On the other hand, when the multiplier was low, bioprinting group demonstrated better fusion of the
the extrusion rate became low as well. At high speed, no scaffold with the surrounding cartilage. This may have
material was extruded, resulting in forming failure; at low resulted from the shape mismatch between implantation
speed, although the material was able to flow through the site and implanted scaffold. The matching degree of the
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needle, the extruded filament was discontinuous, which implanted scaffold has a significant effect on the success of
also caused invalid forming. In the case of low-speed the surgery. 13,36 In particular, the defect was not as round
printing and under an optimal extrusion rate, the slow as the preformed scaffold. Due to this mismatching, a void
movement of the printing head resulted in a longer time existed in the direct implantation group after implantation.
required for the head to travel a certain distance. Therefore, The existence of the void resulted in local instability,
under the same extrusion rate, there was excessive extrusion looseness, and detachment of the scaffold, which were not
material, making the filament thicker. When the printing conducive to tissue regeneration. 52,53 Consequently, the
speed was too fast, the extruded filament was pulled due regeneration in the direct implantation group was not as

Volume 10 Issue 1 (2024) 392 https://doi.org/10.36922/ijb.1437