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Prostate cancer (PCa) that progresses after androgen deprivation therapy (ADT) remains incurable. The underlying mechanisms that account for the ultimate emergence of resistance to ADT, progressing to castrate-resistant prostate cancer (CRPC), include those that reactivate androgen receptor (AR), or those that are entirely independent or cooperate with androgen signaling to underlie PCa progression. The intricacy of metabolic pathways associated with PCa progression spurred us to develop a metabolism-centric analysis to assess the metabolic shift occurring in PCa that progresses with low AR expression. We used PCa patient-derived xenografts (PDXs) to assess the metabolic changes after castration of tumor-bearing mice and subsequently confirmed main findings in human donor tumor that progressed after ADT. We found that relapsed tumors had a significant increase in fatty acids and ketone body (KB) content compared with baseline. We confirmed that critical ketolytic enzymes (ACAT1, OXCT1, BDH1) were dysregulated after castrate-resistant progression. Further, these enzymes are increased in the human donor tissue after progressing to ADT. In an in silico approach, increased ACAT1, OXCT1, BDH1 expression was also observed for a subset of PCa patients that relapsed with low AR and ERG (ETS-related gene) expression. Further, expression of these factors was also associated with decreased time to biochemical relapse and decreased progression-free survival. Our studies reveal the key metabolites fueling castration resistant progression in the context of a partial or complete loss of AR dependence.

3D printing for tissue engineering requires biomaterials with mechanical and biological properties suitable for both tissue regeneration and the printing process. A filament made of poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) combined with 45S5 Bioglass (BG) was used to print 3D scaffolds by fused deposition modeling (FDM). Chemical treatment of BG particles with chlorotrimethylsilane (CTMS) improved the ductility of the extruded filaments and allowed excellent printability. Controlling the printing parameter infill density (I%), from 20 to 90%, scaffolds were obtained with interconnected pores and channel sizes in the 100–800 µm range and exhibiting tensile modulus from 0.25 to 1.36 GPa. PHBV + BG scaffolds and PHBV scaffolds coated with CTMS treated BG particles, as a model of a rough and biologically active coating, showed no cytotoxic effects, and cells preferred the scaffolds containing BG in terms of cell spreading. Mechanical and biological properties of the scaffolds were similar to those of the extracellular matrix (ECM) of trabecular bone.