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3D Printing of hydrogel composite systems: Recent advances in technology for tissue engineering

A tunable degradation rate for hydrogels has also been 3.2 Particle-reinforced Hydrogel Composites 3D
thoroughly investigated so as to provide a tissue scaffold Printing
platform which gradually degrades over a few months Incorporation of micro- or nanoparticles into the hydrogel
as well as sufficient mechanical resistance. p(HPMAm- is widely used to enhance the mechanical and biological
lactate)/PEG hydrogel composites are printed with properties of pure hydrogels due to their low cost, ease of
3D plotting method by Censi et al. [78] These hydrogel preparation, and isotropic strengthening behaviors [11,12] . A
composites were crosslinked by thermal gelation and particle-reinforced hydrogel composite is often formed from ex
chemical crosslinks to stabilize the structure. Complete situ process in which the pre-formed or pre-purchased particles
degradation of the printed scaffold was achieved in are dispersed into a hydrogel-forming liquid to be used for
190 days. In addition, the fabricated scaffolds showed 3D printing (Figure 5A). This approach allows excellent
similar mechanical characteristic with natural semi- control over the quantity of incorporated particles and greatly
flexible hydrogels such as collagen and displayed high facilitates the study of optimal experiment conditions. Most
chondrocytes viability after 1 and 3 days. Shie et al. also particle-reinforced hydrogel composites are fabricated by
attempted to modify the degradation rate of hydrogels this approach. For example, Fedorovich et al. used biphasic
through a 3D printed polyurethane (PU)/HAc scaffold calcium phosphate (BCP) microparticles in the range of
[82]
for use in cartilage tissue engineering . The water-based 106–212 μm for composite reinforcement and Matrigel or
polyurethane (PU) with varying contents of HAc were alginate as the hydrogel matrix. This particle-reinforced
printed by DLP process. The diametral tensile strength hydrogel composite was implanted in bone defects and used as
and elastic modulus of PU/HAc hydrogel composite are an osteoinductive bone filler. Within 6 weeks of implantation,
higher than those of pure PU hydrogel. After 28 days early osteogenesis of incorporated multi-potent stromal cells
of degradation test, PU/HAc hydrogel composites with (MSCs) was induced. For 3D printing of particle-reinforced
varying concentrations of HAc all exhibited similar composites, nozzle sizes bigger than the microparticle size (420
degradation profiles. However, in the case of PU/HAc um internal diameter) were used and a 10-layer 3D scaffold
hydrogel composite scaffolds with over 2% of HAc, (10 × 20 × 1 mm) was fabricated via a 3D-bioplotter system.
scaffolds showed ductile behavior even after 28 days of In the case of coarse microparticle-hydrogel composites,
degradation. Meanwhile PU hydrogel and PU/1% HAc the mechanical enhancement is much lower compared to
hydrogel demonstrated brittle behavior after degradation composites containing nano-sized particles, but it is easier to
suggesting that the addition of HAc facilitated the stable get a uniform particle distribution within the hydrogel through
degradation of hydrogel composite scaffolds. simple mixing due to its relatively low surface-to-volume

Figure 5. Schematic diagram of ex-situ and in-situ approaches for particle-reinforced hydrogel composite fabrication

12 International Journal of Bioprinting (2018)–Volume 4, Issue 1