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characteristics (Table 2). Aβ peptides. Similarly, Park et al. incorporated astrocytes
97
and microglia into a Matrigel culture system, successfully
3.2.1. Matrigel modeling AD-related neuroinflammation. Matrigel is
Matrigel, a widely used biomaterial in cell culture systems, a popular choice for creating vascularized organoids
plays a pivotal role in BOs’ culture. Rich in growth due to its ability to imitate the extracellular matrix, thus
factors and ECM proteins, Matrigel provides essential creating a supportive environment for cell growth and
biochemical cues for cell differentiation, polarization, differentiation. 98,99 It promotes the formation of vascular
and the formation of organoid-like structures. Lancaster networks by supporting ECs’ growth and organization,
95
et al. first demonstrated that Matrigel enables hiPSCs allowing these cells to self-organize into blood vessel-like
4
to self-organize into 3D BOs, mimicking the cellular structures. However, Matrigel alone has been found to be
complexity of the developing human brain. In addition inadequate for supporting vascular lumens. Therefore,
to providing structural support, Matrigel mimics the researchers combined Matrigel with ECs, microfluidics
properties of the native brain ECM, facilitating the platforms, and in vivo transplantation to construct
maturation of neural networks. Kim et al. showed that vascularized organoids more effectively. 100
96
BOs cultured in 3D Matrigel promoted the aggregation of

Table 2. Biomaterials supporting brain organoid development and vascularization
Biomaterials Stem Cells Methods Key founding Advantages Limitations References
Matrigel iPSCs and Co-culture and Vascularization of brain Rich in laminin, Extracted from 18
hiPSCs-derived in vivo organoids with UC Davis collagen IV, and EHS mouse
ECs patient’s own ECs growth factors, sarcoma;
hESCs/hiPSCs Co-culture and V-Organoids are integrated closely resembling Matrigel exhibits 83
and HUVECs in vivo with the mouse vasculature, the native basement compositional
creating functional membrane; inconsistencies;
human-mouse blood vessels Supports neural Matrigel variable
and endothelial bioactive
hiPSCs and Co-culture and Directed incorporation of attachment, components limit 84
MPC in vivo MPCs into neural organoids migration, reproducibility and
leads to the formation of and lineage standardization; As
organized blood vessels with commitment; a murine-derived
a hierarchical structure, Promotes ECM, it may
mimicking natural vasculature endothelial network not fully
formation and replicate human
host vasculature physiological
integration in vivo conditions
dECM hiPSCs 3D culture with BEM enhances neurogenesis Provides a bioactive Preparation 144
microfluidic and cortical structure and physiologically complexity and
system formation and reduces cell relevant batch-to-batch
death; Ventricle-like structures microenvironment; variability limit
and neural development are More biomimetic reproducibility
optimized in a dynamic culture than Matrigel;
hiPSCs Embedded in Supports neurogenesis Promotes a 117
B-ECM-based and structural formation, long-term culture
hydrogel similar to Matrigel but with
a more native-like cellular
environment
Collagen hiPSCs Embedded in The application of neuronal Well-characterized Lacks the 132
collagen type plasticity and modeling of structure; biochemical
I with growth disease Widely used for complexity
factors scaffold-based required for full
hiPSCs Embedded in Microenvironmental role in neuroengineering; ECM mimicry 133
collagen type I brain tumor progression Promotes
with VEGF and endothelial cell
FGF-2 migration and
vascular integration
Abbreviations: BEM: Brain extracellular matrix; B-ECM: Brain-derived extracellular matrix; dECM: decellularized extracellular matrix;
ECM: Extracellular matrix; ECs: Endothelial cells; EHS: Engelbreth–Holm–Swarm; FGF: Fibroblast growth factor; hESCs: Human embryonic stem cells;
hiPSCs: Human induced pluripotent stem cells; HUVECs: Human embryonic stem cells; iPSCs: Induced pluripotent stem cells; MPC: Mesodermal
precursor cell; UC: University of California; VEGF: Induced pluripotent stem cells; V-Organoids: Vascularized organoids; 3D: Three-dimensional.

Volume 1 Issue 2 (2025) 12 doi: 10.36922/or.8162