Revolutionizing cancer care: Bioprinting prostate cancer stem cells for targeted treatments

Table 1 Comparison of Traditional and 3D bioprinted models in exploring prostate cancer stem cell microenvironment and therapeutic resistance

Traditional models	3D bioprinted models
2D cell cultures- lack tumor architecture- no microenvironment mimicry	3D architecture- mimics in vivo structures- maintains ECM and gradients
Animal models-species differences- limited personalization	Patient-specific models- derived from patient cells- enables personalized medicine
Simplistic TME- Incomplete PCSC interactions- low cell heterogeneity	Complex TME- includes stromal & immune cells- High fidelity of PCSC niche
Static drug testing- poor predictability- no adaptive mechanisms	Dynamic drug screening- mimics drug diffusion & hypoxia- Real-time therapy testing
Limited resistance modeling- misses EMT, hypoxia response	Therapy resistance replication- includes hypoxia, EMT, cytokine crosstalk
Slow, costly translational gaps	High-throughput & scalable- faster treatment planning- organ-on-chip integration possible

PCSC: Prostate cancer stem cell; EMT: Epithelial–mesenchymal transition.

Table 2 Challenges in bioprinting prostate cancer stem cell models: Technical and clinical perspectives

Category	Challenge	Scientific context
Bioink engineering	Inadequate mimicry of prostate ECM and mechanical inconsistencies	Balancing stiffness and porosity to maintain PCSC phenotype and niche interactions
Cell viability and distribution	Cellular stress during extrusion and uneven cell dispersal	Shear stress impairs PCSC survival and may affect expression of stemness-related markers
Recapitulation of niche	Incomplete integration of stromal cells, hypoxia and cytokine signaling	Limitation in modeling immune- evasive and therapy -resistant PCSC microenvironment
Standardization & scalability	Difficulty in reproducing constructs with consistent geometry and cellular organization	Affects comparative drug screening and reproducibility across platforms
Vascularization limitations	Lack of functional vasculature in vitro impedes nutrient perfusion and long-term culture	Hinders tumor model viability for chronic drug studies and metastasis research
Clinical translation	Limited alignment with clinical tumor heterogeneity and patient-specific responses	Necessitates integration with omits data and patient-derived cells to improve predictive value

PCSC: Prostate cancer stem cell; ECM: Extracellular matrix.