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Filament Structure, 3D printing, Bone Repair Scaffolds
4.1. Cartilage followed by a near-field direct writing technique to prepare

The skeletal system consists primarily of bones, cartilage, polymer meshes immobilized in the ceramic ink and
embedded in cell-laden GelMA (Figure 6C). The several
and bands of fibrous connective tissue (i.e. tendons and
ligaments). Cartilage is a highly specific tissue with no microfiber structures prepared as crosslinker resulted
in more than 6.5-fold increase in bond strength at the
blood supply, nerve tissue, or lymphatic vessels, and hydrogel-ceramic interface, and the Melt Electrowriting
once injured, it cannot regenerate spontaneously in the lattices imparted cartilage structures with compressive
body [128] . Calcified cartilage is found in the deepest part of properties close to those of natural cartilage (20 times that
the natural cartilage tissue, connecting the cartilage to the of the original hydrogel), in addition, cells remained viable
underlying subchondral bone [129] . Cartilage defects usually within the microfiber reinforced GelMA and the deposition
include damage to surface articular cartilage, intermediate of cartilage-like extracellular matrix was observed in both
calcified cartilage, and deep subchondral bone [130] . Driven
by the growing medical demand, the number of patients structures after 6 weeks of culture. Kim et al. and Hong
[137,138]
requiring functional bone grafting is also increasing, with et al. synthesized a light-curable bioink material, that
at least 500,000 patients receiving bone defect repair is, glycidyl methacrylate modified silk protein (Sil-MA),
st
annually worldwide [131] . Therefore, bioprinting of skeletal for the 1 time. It was found that the compressive modulus
tissues such as cartilage is one of the main areas of increased about 2.6 times for every 10% increase in Sil-
MA concentration, and the compressive breaking stress
interest in the field of tissue engineering and regenerative was up to 910 kPa and the tensile fracture stress was up
medicine. In contrast, traditional treatment methods are to 50 kPa for a 30% concentration of Sil-MA hydrogel; an
complicated and not only lead to a lack of biomechanical
function of fibrocartilage, but also have limitations in extended epithelial matrix was found around the Sil-MA
terms of cost and side effects. With the development of hydrogel in rabbit tracheal defect experiments, confirming
cartilage engineering, the construction and grafting of that the Sil-MA hydrogel replaced the defective part of the
cartilage composites is considered an effective method to trachea part of the trachea and guided the regeneration of
treat osteochondral (OC) defects [132,133] . the trachea.
Recently, Chen et al. [134] designed and successfully 4.2. Vascular
fabricated a three-layer gradient cartilage scaffold by
physical cross-linking, photo-cross-linking, and chemical Bone tissue repair requires nutrient and oxygen delivery
cross-linking for the 1 time, and the addition of nHA and the ability to remove waste products in a timely
st
effectively improved the tensile properties of the scaffold manner to maintain necessary functions and nutrient
(up to 160 kPa). With the increase of nHA concentration, supplies [139-141] . Therefore, the introduction of vascular-
the compressive strength of the scaffold also increased, like structures is a prerequisite for the successful
and the compressive strength of nHA scaffold with 70% design of functional tissues suitable for regeneration
nHA content can reach 0.65 MPa, which is about 5 times and the construction in in vitro models [142] . Achieving a
of 40% nHA content. The ICRS (International Cartilage directed design of vascular growth structures remains
Repair Society) score was the highest in the 70% nHA a great challenge, and pre-creating microstructures
+ BMSC group. Sun et al. [135] printed gradient scaffolds with customized microtissues (e.g. interconnected
with PCL and wrapped BMP 4 and TGF-β3 into PLGA microchannels) to mimic the vascular system that
microspheres, and encapsulated them into hydrogels along provides a survival environment for the surrounding
with bone marrow MSCs (BMSCs), which were injected stromal cells remains a feasible solution.
into the PCL fiber gap. To better simulate the full cartilage To achieve this goal, researchers have explored cell-
structure, the deepest layer was the hydrogel wrapped with laden printing techniques to ensure precise control of the
BMP4, while the upper layer was the hydrogel wrapped spatial arrangement of vascular cells in the matrix. Jia
with TGF-β3. The characterization results showed that the et al. [143] used bioinks made of GelMA, sodium alginate
scaffold had well connectivity and biocompatibility, and and 4-arm poly(ethylene glycol)-tetra-acrylate to deposit
the PCL support structure provided a suitable environment implantable vascular structures with highly ordered
for cell distribution, nutrient supply, and proliferation and arrangements in one step by a coaxial extrusion device.
differentiation. In addition, the gradient scaffold formed The percentage of surviving cells under UV experiments
bone-like tissue (4 times that of the non-gradient scaffold) exceeded 80%, and longer UV irradiation reduced the
in whole layers after 12 weeks of in vitro culture, and its scaffold degradation rate. Suntornnond et al. [144] designed
Young’s modulus and mechanical properties were close and fabricated highly printable hydrogel composites
to those of normal cartilage tissue. Diloksumpan et al. [136] using Planic-127 and GelMA to prepare mimic vascular-
integrated hydrogel, ceramic, and polymer materials to like scaffold structures by 3D extrusion-based printing
fabricate a calcium phosphate-based bioceramic ink into method, and in vitro evaluation showed that after 7 days
a subchondral bone substitute using extrusion printing, of co-culture, the highest number of cells survived

54 International Journal of Bioprinting (2021)–Volume 7, Issue 4