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International Journal of Bioprinting Medical regenerative in situ bioprinting

good mechanical properties and pore size distribution, but viability after injection. Some materials, such as platelet-
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it is not sufficient to control the position and geometry of rich plasma (PRP), have been investigated for hydrogel
the microvascular network. To improve vascularization, integration. Zhao et al. incorporated PRP into sodium
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it is necessary to form a predetermined microchannel in alginate/gelatin bioink for repairing skin defects by
the printed structure. Mostafavi et al. used high-speed releasing various growth factors and active ingredients.
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stirring to control the pore size and distribution of bioinks. However, PRP degrades rapidly in the wound environment
Coaxial printing, used to fabricate hollow structures and and cannot sustainably release growth factors. Lai et al.
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predetermined microchannels, has the disadvantage of prepared a dressing with three layers of core-shell fiber
low resolution. There are studies using sacrificed-template through coaxial 3D printing and fixed PRP in the core
to print structures with submicron-sized capillaries. This layer of the fiber to achieve continuous release of growth
method leverages the different solubility or temperature factors. By optimizing bioink characteristics, in situ
sensitivity of two bioinks, such as GelMA/poly(ethylene bioprinting can be further developed and expanded for
oxide) or GelMA/gelatin bioinks. After printing the various applications in tissue engineering and regenerative
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bioinks side by side, the sacrificial bioink is removed, medicine. The bioinks currently used for in situ bioprinting
retaining the desired structure. However, this method and their specific applications in tissue engineering are
is insufficient to develop complex structures. Enrico summarized in Table 3. Based on the bioink sources, the
et al. proposed a method of cavitation molding using materials reported for in situ bioprinting can be divided
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femtosecond infrared laser pulses to generate cavitation into either natural or synthetic polymers.
bubbles in the bioink to form microchannels, subsequently
filling them with endothelial cell suspension to form 3.2. Challenges
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continuous cell layers after cell culture. Current bioink research faces challenges such as viscosity,
rheological properties, 73,81 and the difficulty of producing
3. Bioinks for in situ bioprinting intricate pores. High-viscosity bioinks can significantly
improve the mechanical strength of printed structures,
3.1. Performance requirements leading to a higher extrusion pressure and lower cell
Bioinks, containing active biomaterials and cells, serve as viability. Although a larger diameter nozzle can be used,
scaffolds to accelerate wound or defect recovery, playing the printing accuracy will be reduced. Thermo-sensitive
an essential role in driving biological interactions. Bioinks bioinks are required to crosslink at body temperature
should meet specific essential characteristics to address for in situ bioprinting. Crosslinked bioinks should
the challenge of complex tissue regeneration effectively. have low mechanical strength to protect cell activity,
Traditional biomaterials have been biocompatible but often but simultaneously require high mechanical strength
lack the ability to effectively promote interactions between to maintain shape and match the defect. Rheological
cells, materials, and tissues. Similarly, bioinks used for properties require optimization according to the properties
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in situ bioprinting should essentially possess remarkable of the material itself, the loaded cells, the bioprinting
rheological properties to enhance the resolution of the approach, bioprinting conditions (e.g., temperature, pH,
printing structure and maintain a specific mechanical and crosslinking mode), and other factors. 43,63,122 Some
strength. Other critical factors include rapid gelation, inks, such as gelatin, have problems creating complex pores
mechanical properties, shape fidelity, biocompatibility, due to their high water content and thermal sensitivity.
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and biofunctionality. 43,63 In some personalized medicine
applications, bioinks should contain autologous bioactive 3.3. Optimization of cellular compatibility and
factors from the patients. Hydrogels have been widely mechanical strength
used as matrices for in situ bioprinting due to their The performance of bioinks varies according to the
excellent biocompatibility, ability to encapsulate cells, in situ bioprinting technology applied. For example,
high permeability, large water content, and similarity inkjet-based in situ bioprinting utilizes bioinks with low
to native ECM. 102–106 The in situ formation of hydrogels viscosity or shear-thinning characteristics to ensure the
has significant advantages over traditional pre-formed smooth formation of droplets, thereby limiting material
hydrogels, such as being minimally invasive, excellent selection. 37,39 Hydrogels with high water content are widely
adaptation to wound margins, accurate filling of defects, used in inkjet-based in situ bioprinting. Additionally, photo-
and simple cell encapsulation. 101,103 Current research crosslinked bioinks, such as GelMA, have reportedly been
primarily focuses on meeting specific characteristics, used in inkjet bioprinting but are prone to nozzle clogging.
such as electroconductivity, 103,107 physiological stimulus- A multiple-nozzle system can be designed to separate the
responsive ability, and shear-thinning ability. 81,105 photoinitiator from the ink, or a coating can be applied to
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Shear-thinning hydrogels are ideal for maintaining cell the nozzle surface to reduce clogging and adhesion.

Volume 10 Issue 5 (2024) 58 doi: 10.36922/ijb.3366