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International Journal of Bioprinting Oozing 3D-printed scaffolds for tissue engineering

tissue replacement. Tissue-engineered constructs or remain unsolved; therefore, soft materials like hydrogels
1,2
scaffolds require mimicking the microenvironment of the are generally utilized for fabrication. 21,27,30
biological extracellular matrix (ECM) niche, composed FDM is one of the most widely utilized 3D printing
of a microfibered complex that contributes to the technologies due to its versatility, simple maintenance,
mechanical support of the tissue. The morphology and and low cost. 31,32 In comparison to others, this technique
3,4
microstructure of scaffolds must satisfy specific mechanical possesses many advantages, including availability of a
and biological requirements including structure material wide range of biodegradable and biocompatible materials
organization, surface morphology, and proper porosity that can be printed, and compatibility with different
(pore size, distribution, and interconnectivity) to CAD software. FDM has a simple working principle: A
promote cell adhesion and proliferation, and subsequent preformed polymeric thermoplastic filament is heated
ECM remodeling. 5,6 to a semiliquid state and then extruded through a
Additive manufacturing technologies (three- nozzle directly onto the building platform following a
dimensional [3D] printing) have become a promising programmed model, with thin layers being deposited
approach to personalized regenerative treatments. These on top of one another. 33-35 Moreover, no toxic solvents
techniques are characterized by their design potential, high are needed to dissolve the polymeric filaments for
speed, and low cost, which allow the fabrication of tissue printing, thus avoiding cell mortality when working with
constructs from the micro- to the macro-scale, providing cell cultures. 36,37 Nevertheless, FDM has certain major
suitable structural and mechanical support for 3D cell constraints such as limited accuracy due to the thickness
cultures, thereby producing new, enhanced tissue. 7-12 of the final extruded filament, the relationship between
Numerous types of constructs have been developed for viscosity and nozzle diameter, or the high temperature
several tissues using 3D printing for regenerative medicine: applied during the melt-extrusion process that may change
38
composites and polymers for bone tissue engineering, 13,14 inherent material properties.
cartilage for the meniscus, or polylactic acid for vascular Limited resolution is, particularly, one of the main
15
grafts, among others. disadvantages in FDM as the accurate impression is
17
16
limited by the nozzle diameter. 39,40 Commonly, these
There are several sorts of additive manufacturing
technologies that generate scaffolds for biomedical nozzle diameters range from 0.8 mm to 0.2 mm, being
unusual to find smaller diameters due to their easy
applications. Traditional modalities, such as fused clogging tendency and subsequent incapacity to ensure
deposition modeling (FDM), selective laser sintering proper flow settings. 41,42 Furthermore, another well-
(SLS), or stereolithography (SLA), among others, allow known drawback of FDM printing occurs when the
18
the creation of components with micro-scaled geometries nozzle deposits a small amount of molten material and
in various materials, such as polymers, composites, and immediately moves to the next position. This movement
metals with high accuracy and reproducibility. 19,20 Despite creates the “stringing” effect or oozing: a very thin “hair”
these advantages, many of these printing conditions are of molten material that extends across the direction of
lethal to cells, such as high temperature or toxic chemicals. travel of the nozzle. 43,44 The oozing effect can be caused
Hence, these techniques commonly generate acellular by a slow retraction speed, overheating in the extruder,
scaffolds that can be utilized for tissue-engineering high printing speed, or very long movements over open
21
purposes by seeding cells after fabrication. spaces, among others. 45-47
In contrast, recent techniques such as 3D bioprinting, The achievement of a microfiber-like environment
in which a suspension of living cells together with represents a major feature to better mimic the tissue ECM
suitable biomaterials and growing factors (bioink) is niche. Several techniques such as electro direct writing,
48
directly deposited to create 3D living tissue, create electrospinning, 49,50 or melt-blowing can create micro-
22
51
interesting soft-tissue constructs, such as composites scaled fibers, but FDM lacks the capacity to generate the
for ear regeneration, or collagen for the human heart, thin required fibers due to the technique’s own limitations.
23
in addition to many others. 24-26 3D bioprinting can be However, recent studies have successfully fabricated various
classified according to American Society for Testing and arrays of microfibers leveraging the oozing effect, by the
Materials (ASTM) into: extrusion-based, jetting-based, manipulation and implementation of certain parameters
28
27
and vat photopolymerization-based. Although these of the printing process, such as the printing speed or the
29
techniques have a variety of applications, including trauma feed rate, and combined them with algorithm-aided design
treatment, whole tissue creation, and in vitro drug testing, (AAD). 44,52 Generally, these approaches can be found as a
several drawbacks including bioink’s dimensional stability, stack of parallel-like patterns with fibers in the range of
limited speed, or cell viability during printing process hundreds of microns, or as a combination of parallel-like
42
Volume 10 Issue 2 (2024) 501 doi: 10.36922/ijb.2337