Page 36 - IJB-9-5

International Journal of Bioprinting 3D bioprinted vascularized tissue models

of this bioprinted metastasis model for drug screening TME. They extended their elegant approach of in-bath
applications by validating the anti-cancer efficacy of coaxial bioprinting, as reported in previous work . The
[63]
the immunotoxin. In another study by Kim et al. , a size-controllable multi-cellular metastatic melanoma
[63]
cancer-vascular platform involving a metastatic cancer spheroids with a perfusable blood and lymphatic vessel
unit and a perfusable vascular system was constructed pair were systematically integrated to develop a 3D
via the embedding and coaxial bioprinting techniques in vitro melanoma model with improved emulation of the
(Figure 4D). Using the former, size-tunable 3D tumor complex TME. The system replicated hallmark events of
spheroids were generated with a high density of melanoma metastatic melanoma, such as tumor–stroma interaction,
cells in the suspension bath matrix of skin dECM, melanoma invasion, and intravasation. In addition, the
mimicking the in vivo scenario (e.g., local invasion, anti-metastatic effect of combinational targeted therapy
central hypoxia, and angiogenic signaling) of metastatic was evaluated by monitoring drug responses based on the
cancer. Through coaxial bioprinting, a vessel-like tubular interaction between melanoma heterospheroids and the
structure was fabricated using HUVECs-laden VdECM/ surrounding TME.
alginate hybrid bioink within skin dECM bath. Thus, 3D Taken together, 3D bioprinting is a promising approach
tumor spheroids with 600 µm diameter and perfusable to generate a reproducible and robust 3D vascularized
vascular channel were directly printed within tissue- tumor model through the elaboration of multi-cellular
specific bath ink with high-precision positioning control constructs within a controlled spatial environment.
in a single step. Such tissue-level cancer-vascular platforms Ultimately, personalized drug screening using
allowing distance control were evaluated to investigate 3D-bioprinted cancer models containing patient-derived
whether positional changes influence cancer progression cells provides an exciting opportunity to navigate clinical
and metastasis, such as epithelial–mesenchymal transition, decision for identifying optimal treatment regimens
endothelial dysfunction, angiogenic sprouting, and specific to individuals. However, all these bioprinted
monocytes recruitment, corroborating the positional platforms still have challenges to be overcome, including
importance in tumor metastasis. This unique bioprinting their level of high-throughput production capability and
approach will likely provide a reliable platform that can poor cellular heterogeneity with genomic stability.
simulate metastatic cancer progression in a more realistic
status in vitro. 3.5. 3D Bioprinting of other vascularized tissue

In addition to engineering perfusable vasculature, models
integrating lymphatic vessels is of a critical aspect to 3D bioprinting has helped spur the development of several
model cancer metastasis. Vascular-lymphatic circulation tissue/organ models for in vitro studies. Other vascularized
systems offer a specialized recycling circuit to the most in vitro tissue models of great interest include bone and
administered anti-cancer drugs in vivo . Cao et al. skin. Few studies have demonstrated their feasibility
[64]
[65]
proposed a breast-cancer-on-a chip platform comprising a in reproducing intricate geometry and representative
hollow blood vessel and a lymphatic vessel pair using coaxial physiological functions of the target tissues.
bioprinting. The pairs of perfusable blood vessel and hollow Considering bone tissue models, 3D bioprinting takes
lymph vessel with one end blinded were fabricated using advantage of the combination of functional vascular
polyethylene glycol diacrylate/alginate/GelMA and eight- and osteogenic components within the construct for
arm poly (ethylene glycol) acrylate/alginate/GelMA inks, vascularized bone tissue formation in vitro. For example,
respectively, with tunable diffusion properties imitating Chiesa et al. reported the in vitro construction of bone
[67]
their native counterparts. Then, the printed tubes and tissue using a gelatin-nanohydroxyapatite (Gel-nHAp),
MCF-7 breast cancer cells were embedded in the GelMA human mesenchymal stem cells (hMSCs), and HUVECs.
matrix to conduct anti-cancer drug (doxorubicin; DOX) Based on a coordinate pattering approach, bone construct
delivery. Using this platform, DOX transport profiles were with an inter-connected pore network was first created
investigated with regard to different combinations of the using Gel-nHAp followed by hMSCs being seeded on
blood and lymphatic vessels and tumor cell arrangements. scaffolds and osteogenically differentiated for 2 weeks.
More recently, Cho et al. constructed a more advanced Then, a suspension containing a 4:1 ratio of hMSCs and
[66]
blood-lymphatic integrated system with heterospheroids HUVECs entrapped in fibrin-GelMA gel was placed in
by employing a combination of embedding and coaxial the macro-pores of the 3D-bioprinted scaffold to induce
bioprinting strategies (Figure 4E). Taking metastatic angiogenesis for 2 weeks. This approach resulted in
melanoma as example, a 3D-bioprinted perfusable blood- developing a self-assembly-driven in vitro vascularized
lymphatic integrated system with heterogeneous spheroids bone model, confirming de novo morphogenesis of
was developed to better recapitulate metastatic melanoma capillary-like networks, vascular lumen formation, and

Volume 9 Issue 5 (2023) 28 https://doi.org/10.18063/ijb.748